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1.
Ann Oncol ; 35(3): 308-316, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38286716

RESUMEN

BACKGROUND: We predicted cancer mortality figures for 2024 for the European Union (EU), its five most populous countries, and the UK. We focused on mortality from colorectal cancer (CRC). MATERIALS AND METHODS: Based on cancer death certification and population data from the World Health Organization and Eurostat databases from 1970 until the most available year, we predicted deaths and age-standardized rates (ASRs) for 2024 for all cancers and the 10 most common cancer sites. We fitted a linear regression to the most recent trend segment identified by the joinpoint model. The number of avoided deaths since the peak in 1988-2024 was estimated for all cancers and CRC. RESULTS: We predicted 1 270 800 cancer deaths for 2024 in the EU, corresponding to ASRs of 123.2/100 000 men (-6.5% versus 2018) and 79.0/100 000 women (-4.3%). Since 1988, about 6.2 million cancer deaths have been avoided in the EU and 1.3 million in the UK. Pancreatic cancer displayed unfavorable predicted rates for both sexes (+1.6% in men and +4.0% in women) and lung cancer for women (+0.3%). The focus on CRC showed falls in mortality at all ages in the EU, by 4.8% for men and 9.5% for women since 2018. The largest declines in CRC mortality are predicted among those 70+ years old. In the UK, projected ASRs for CRC at all ages are favorable for men (-3.4% versus 2018) but not for women (+0.3%). Below age 50 years, CRC mortality showed unfavorable trends in Italy and the UK, in Poland and Spain for men, and in Germany for women. CONCLUSIONS: Predicted cancer mortality rates remain favorable in the EU and the UK, mainly in males due to earlier smoking cessation compared to females, underlining the persisting major role of tobacco on cancer mortality in Europe. Attention should be paid to the predicted increases in CRC mortality in young adults.


Asunto(s)
Neoplasias Colorrectales , Neoplasias Pulmonares , Neoplasias , Masculino , Adulto Joven , Humanos , Femenino , Persona de Mediana Edad , Anciano , Europa (Continente)/epidemiología , Neoplasias/epidemiología , Predicción , Alemania , Mortalidad
2.
Ann Oncol ; 34(4): 410-419, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36882139

RESUMEN

BACKGROUND: We predicted cancer mortality figures for 2023 for the European Union (EU-27), its five most populous countries, and the UK. We also focused on mortality from lung cancer. MATERIALS AND METHODS: Using cancer death certification and population data from the World Health Organization and Eurostat databases for 1970-2018, we predicted numbers of deaths and age-standardized rates (ASRs) for 2023 for all cancers combined and the 10 most common cancer sites. We investigated the changes in trends over the observed period. The number of avoided deaths over the period 1989-2023 were estimated for all cancers as well as lung cancer. RESULTS: We predicted 1 261 990 cancer deaths for 2023 in the EU-27, corresponding to ASRs of 123.8/100 000 men (-6.5% versus 2018) and 79.3 for women (-3.7%). Over 1989-2023, ∼5 862 600 cancer deaths were avoided in the EU-27 compared with peak rates in 1988. Most cancers displayed favorable predicted rates, with the exceptions of pancreatic cancer, which was stable in EU men (8.2/100 000) and rose by 3.4% in EU women (5.9/100 000), and female lung cancer, which, however, tends to level off (13.6/100 000). Steady declines are predicted for colorectal, breast, prostate, leukemia, stomach in both sexes, and male bladder cancers. The focus on lung cancer showed falls in mortality for all age groups in men. Female lung cancer mortality declined in the young (-35.8%, ASR: 0.8/100 000) and middle-aged (-7%, ASR: 31.2/100 000) but still increased by 10% in the elderly (age 65+ years). CONCLUSIONS: The advancements in tobacco control are reflected in favorable lung cancer trends, and should be pushed further. Greater efforts on the control of overweight and obesity, alcohol consumption, infection and related neoplasms, together with improvements in screening, early diagnosis, and treatments may achieve a further 35% reduction in cancer mortality in the EU by 2035.


Asunto(s)
Leucemia , Neoplasias Pulmonares , Neoplasias , Neoplasias Pancreáticas , Anciano , Persona de Mediana Edad , Humanos , Masculino , Femenino , Neoplasias/epidemiología , Unión Europea , Organización Mundial de la Salud , Mortalidad , Europa (Continente)/epidemiología
3.
Eur J Neurol ; 28(2): 567-578, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33058344

RESUMEN

BACKGROUND AND PURPOSE: In relapsing-remitting multiple sclerosis patients (RRMS) disability progressively accumulates over time. To compare the cumulative probability of 6-month confirmed disability-worsening events using a fixed baseline or a roving Expanded Disability Status Scale (EDSS) reference, in a real-world setting. METHODS: A cohort of 7964 RRMS patients followed for 2 or more years, with EDSS scores recorded every 6 months, was selected from the Italian Multiple Sclerosis Register. The overall probability of confirmed disability-worsening events and of confirmed disability-worsening events unrelated to relapse was evaluated using as reference a fixed baseline EDSS score or a roving EDSS score in which the increase had to be separated from the last EDSS assessment by at least 6 or 12 months. RESULTS: Using a fixed baseline EDSS reference, the cumulative probability of 6-year overall confirmed disability-worsening events was 33.2%, and that of events unrelated to relapse was 10.9% (33% of overall confirmed disability-worsening events). Using a roving EDSS, the proportions were respectively 35.2% and 21.3% (61% of overall confirmed disability-worsening events). CONCLUSIONS: In a real-world setting, roving EDSS reference scores appear to be more sensitive for detecting confirmed disability-worsening events unrelated to relapse in RRMS patients.


Asunto(s)
Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Estudios de Cohortes , Evaluación de la Discapacidad , Humanos , Italia/epidemiología , Esclerosis Múltiple Recurrente-Remitente/diagnóstico , Esclerosis Múltiple Recurrente-Remitente/epidemiología
5.
Ann Oncol ; 31(5): 558-568, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32272209

RESUMEN

BACKGROUND: Aspirin has been associated with a reduced risk of colorectal cancer, and possibly of a few other digestive tract cancers. The quantification of risk reduction and the optimal dose and duration of aspirin use for the prevention of colorectal and other digestive tract cancers remains unclear. METHODS: To provide an up-to-date quantification of this association, we conducted a systematic review and meta-analysis of all observational studies on aspirin and cancers of the digestive tract sites published through March 2019. We estimated the pooled relative risk (RR) of cancer for regular aspirin use versus non-use using random-effects models, and, whenever data were available, we investigated the dose- and duration-risk relations. RESULTS: Regular aspirin use is associated with a reduced risk of colorectal cancer [RR = 0.73, 95% confidence interval (CI) = 0.69-0.78, 45 studies], squamous-cell esophageal cancer (RR = 0.67, 95% CI = 0.57-0.79, 13 studies), adenocarcinoma of the esophagus and gastric cardia (RR = 0.61, 95% CI = 0.49-0.77, 10 studies), stomach cancer (RR = 0.64, 95% CI = 0.51-0.82, 14 studies), hepato-biliary tract cancer (RR = 0.62, 95% CI = 0.44-0.86, five studies), and pancreatic cancer (RR = 0.78, 95% CI = 0.68-0.89, 15 studies), but not of head and neck cancer (RR = 0.94, 95% CI = 0.76-1.16, 10 studies). The associations are somewhat stronger in case-control than in cohort and nested case-control studies and are characterized by some between-study heterogeneity. Risk estimates are consistent across sex, geographical areas, and other selected covariates. For colorectal cancer, an aspirin dose between 75 and 100 mg/day conveys a risk reduction of 10%, and a dose of 325 mg/day of 35%. For all neoplasms, except head and neck cancer, inverse duration-risk relations with aspirin use are found. CONCLUSION: The present comprehensive meta-analysis supports and further quantifies the inverse association between regular aspirin use and the risk of colorectal and other digestive tract cancers, including some rare ones. The favorable effect of aspirin increases with longer duration of use, and, for colorectal cancer, with increasing dose.


Asunto(s)
Neoplasias Colorrectales , Neoplasias Gastrointestinales , Aspirina , Estudios de Cohortes , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/prevención & control , Neoplasias Gastrointestinales/epidemiología , Neoplasias Gastrointestinales/prevención & control , Humanos
6.
Diabetes Res Clin Pract ; 146: 172-179, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30332619

RESUMEN

BACKGROUND AND AIMS: There are concerns that incretin-based antidiabetic drugs - including dipeptidyl peptidase 4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists - increase the risk of hospitalization for heart failure (HF). To further analyse this issue, we conducted a nested case-control study within a cohort of antidiabetic users in a real world setting. METHODS AND RESULTS: Within a cohort of 133,639 subjects with a first prescription of an antidiabetic drug (new-users) between 2010 and 2016 in Lombardy, Italy, and were followed-up to 2016, we identified 4057 subjects with a first hospitalization for HF and 80,450 controls matched on sex, age, and date of cohort-entry. The multivariate odds ratios (ORs) of HF in relation to current use of incretin-based drugs as compared to current use of two or more oral antidiabetics was 1.06 (95% confidence interval, CI, 0.83-1.35), with no evidence of a trend in risk with increasing duration of use. The corresponding ORs were 1.10 (95% CI 0.85-1.41) for DPP-4 inhibitors and 0.84 (95% CI 0.48-1.47) for GLP-1 receptor agonists. Estimates were consistent in various sensitivity analyses. CONCLUSIONS: This study indicates that incretin-based drugs are not associated with an increased risk of hospitalization for HF, thus providing further reassurance on the cardiovascular safety of these antidiabetic drugs in the clinical practice.


Asunto(s)
Insuficiencia Cardíaca/terapia , Incretinas/efectos adversos , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Insuficiencia Cardíaca/patología , Hospitalización , Humanos , Masculino , Persona de Mediana Edad
7.
Int J Immunopathol Pharmacol ; 26(4): 961-4, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24355232

RESUMEN

Multiple Chemical Sensitivity (MCS) is characterised by the appearance of numerous and sometimes severe symptoms, when subjects are in contact with various chemicals and medicinal substances. Currently there are no useful guidelines for managing clinical issues and, specifically, anaesthesia for patients with MCS. This case report describes anaesthesia management in a patient affected by clinically documented MCS and a latex allergy, a candidate for a laparoscopic cholecystectomy operation.


Asunto(s)
Anestesia General/métodos , Sensibilidad Química Múltiple/complicaciones , Colecistectomía Laparoscópica , Femenino , Humanos , Hipersensibilidad al Látex/complicaciones , Persona de Mediana Edad
9.
Radiat Prot Dosimetry ; 127(1-4): 526-30, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17578873

RESUMEN

Dosimetric impact studies aim at evaluating potential radiological effects of chronic or acute releases from nuclear facilities. A methodology for ranking radionuclides (RN) in terms of their health-related impact on the human population was first developed at CEA with specific criteria for each RN that could be applied to a variety of situations. It is based, in particular, on applying physico-chemical criteria to the complete RN inventory (present in the release or in the source term) and on applying norms related to radiation protection and chemical toxicology. The initial step consisted in identifying and collecting data necessary to apply the methodology, with reference to a previous database of long-lived radionuclides (LLRN, with half-lives ranging from 30 to 10(14) y) containing 95 radionuclides. The initial results have allowed us to identify missing data and revealed the need to complete the study for both toxic and radiotoxic aspects. This led us to the next step, developing a specific database, DAtabase for Chemical Toxicity and Radiotoxicity Assessment of RadIonuclides (DACTARI), to collect data on chemical toxicity and radiotoxicity, including acute or chronic toxicity, the chemical form of the compounds, the contamination route (ingestion, inhalation), lethal doses, target organs, intestinal and maternal-foetal transfer, drinking water guidelines and the mutagenic and carcinogenic properties.


Asunto(s)
Bioensayo , Sistemas de Administración de Bases de Datos , Bases de Datos Factuales , Radioisótopos/clasificación , Radioisótopos/envenenamiento , Medición de Riesgo/métodos , Recuento Corporal Total , Almacenamiento y Recuperación de la Información/métodos , Factores de Riesgo
10.
Pharm. care Esp ; 8(3): 107-111, jul.-sept. 2006. ilus, tab
Artículo en Es | IBECS | ID: ibc-68650

RESUMEN

Las intervenciones farmacéuticas tienen como objetivo detectar problemas existentes o potenciales relacionados con los medicamentos e intervenir para resolverlos. En el presente trabajo se realizó un estudio prospectivo a fin de cuantificar y clasificar las intervenciones farmacoterapéuticas registradas en un período de 10 semanas. Nuestros resultados muestran que fue elevado (137) el número de problemas relacionados con los medicamentos que se hubieran obviado sin la intervención del farmacéutico. Se observó que el grado de aceptación de las intervenciones totales fue del 85,5%. Estos resultados indican la necesidad de aumentar la integración y establecer relaciones de cooperación con los demás profesionales para poder brindar un mejor servicio dentro del sistema (AU)


The object of the pharmaceutical interventions is to detect the real or potential problems related to drugs and to take part to resolve them. In the present work, it was carried out a prospective study in order to quantify and to classify the registered pharmacotherapeutic interventions in a period of 10 weeks. Our results indicate that the number of problems related to the drugs was high (137) that had been obviated without the intervention of the pharmacist. It was observed that the degree of acceptance of the total interventions was 85,5%. These result indicated the need to increase the integration and to establishing relations of cooperation with the other professionals to be able to offer a better service within the system (AU)


Asunto(s)
Humanos , Servicios Farmacéuticos , Ensayo Clínico , Estudios Prospectivos , Hospitales Universitarios
11.
Am J Cardiol ; 78(2): 197-202, 1996 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-8712142

RESUMEN

To determine the independent prognostic significance of left ventricular (LV) mass and geometry (concentric vs eccentric pattern) in hypertensive subjects with LV hypertrophy at echocardiography, 274 subjects were followed for up to 8.7 years (mean 3.2). All patients had systemic hypertension and LV mass > or = 125 g/body surface area (BSA) and underwent ambulatory blood pressure (BP) monitoring and echocardiography before treatment. Eccentric and concentric hypertrophy were defined by the ratio between LV posterior wall thickness and LV radius at telediastole <0.45 and > or = 0.45, respectively. Age, sex ratio, body mass index, office BP and serum glucose, cholesterol, and triglycerides did not differ between the groups with eccentric (n=145) and concentric (n=129) hypertrophy. Average 24-hour daytime, and nighttime systolic ambulatory BPs were higher in concentric than in eccentric hypertrophy (all p <0.01). LV mass was slightly greater in concentric than in eccentric hypertrophy (157 vs 149 g/BSA, p <0.05). Endocardial and midwall shortening fraction were lower in concentric than in eccentric hypertrophy (96.5% vs 106.0% of predicted and 71.4% vs 89.7% of predicted, respectively; both p <0.01). The rate of major cardiovascular morbid events was 2.20 and 3.34 per 100 patient-years in eccentric and concentric hypertrophy, respectively (log rank test, p=NS). Age >60 and LV mass above median (145 g/BSA) were significant adverse prognostic predictors, while LV geometry (eccentric vs concentric hypertrophy) and ambulatory BP were not. The event rates per 100 patient-years were 1.38 and 3.98, respectively, in the patients with LV mass below and above median (age-adjusted relative risk 2.70; 95% confidence interval [CI] 1.03 to 6.63; p=0.015). In hypertensive subjects with established LV hypertrophy, LV mass, but not its geometric pattern, provides important prognostic information independent of conventional risk markers including office and ambulatory BP.


Asunto(s)
Ventrículos Cardíacos/patología , Hipertensión/complicaciones , Hipertrofia Ventricular Izquierda/complicaciones , Presión Sanguínea , Supervivencia sin Enfermedad , Ecocardiografía , Humanos , Hipertensión/mortalidad , Hipertrofia Ventricular Izquierda/mortalidad , Hipertrofia Ventricular Izquierda/patología , Hipertrofia Ventricular Izquierda/fisiopatología , Morbilidad , Pronóstico
12.
Blood Press Monit ; 1(1): 3-11, 1996 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-10226196

RESUMEN

BACKGROUND: Blood pressure variability is a determinant of target organ damage in essential hypertension, but its independent prognostic significance has not yet been assessed in prospective studies of cardiovascular morbidity and mortality. OBJECTIVE: To assess the relationship between blood pressure variability, assessed non-invasively using 24 h ambulatory blood pressure monitoring and subsequent incidence of cardiovascular morbid events in persons with essential hypertension. DESIGN: Prospective observational study. PATIENTS AND METHODS: We followed for up to 8.6 years (mean 2.92) 1372 individuals with essential hypertension whose initial off-therapy diagnostic work-up included 24 h non-invasive ambulatory blood pressure monitoring. Those with a standard deviation of daytime or night-time blood pressure below or above the group mean were classified as having low or high blood pressure variability, respectively. One hundred and eighty-two participants underwent repeated ambulatory blood pressure monitoring and echocardiography during follow-up, 2.7 years later. RESULTS: Target organ damage score was greater in the participants with high variability of daytime (P = 0.004) and night-time (P = 0.011) systolic blood pressure than in those with low blood pressure variability. In those who underwent repeated echocardiography, for every quartile of baseline ambulatory blood pressure, left ventricular mass at follow-up was greater (all P < 0.05) in those with high baseline blood pressure variability than in those with low baseline variability. During follow-up there were 106 major cardiovascular morbid events. Event rate was 1.99 and 3.26 events per 100 patient-years, respectively, in participants with low and high variability of daytime systolic pressure and 1.98 and 3.38 events per 100 patient-years, respectively, in those with low and high variability of night-time systolic pressure (log-rank test: both P < 0.05). However, in a Cox multivariate analysis, the variability score for daytime and night-time systolic pressure failed to enter the model (age, diabetes mellitus, previous cardiovascular events and average night-time systolic pressure were independently associated with cardiovascular events). CONCLUSION: Increased blood pressure variability, assessed with non-invasive monitoring, is associated with a higher incidence of cardiovascular morbid complications of hypertension, but also with a higher blood pressure, older age and a higher prevalence of diabetes mellitus. Because of the relevant predictive effect of these associated factors, the adverse prognostic significance of increased blood pressure variability is no longer detectable in multivariate analysis.

13.
Arch Gerontol Geriatr ; 21(2): 205-14, 1995.
Artículo en Inglés | MEDLINE | ID: mdl-15374216

RESUMEN

In order to evaluate the prevalence of non-suppression after dexamethasone in psychogeriatrics and to further verify the reliability of the neurobiological information obtained, dexamethasone suppression test was carried out in a geriatric population composed of patients with dementia of Alzheimer type, vascular dementia, stroke and age and sex-matched controls. Basal cortisol levels did not differ among groups and was positively correlated to age. Prevalence of non-suppression, defined according to Carroll's criterion was high in the pathological groups studied, and relatively high in controls, showing no diagnostic value. Unlikely suppressors, the time course of mean plasma corticol levels of non-suppressors was highly heterogeneous in each group considered, especially in the pathological groups. More restrictive criteria for the definition of non-suppressors are proposed, in order to increase the specificity of the test when applied to psychogeriatrics.

14.
Calcif Tissue Int ; 56(5): 410-4, 1995 May.
Artículo en Inglés | MEDLINE | ID: mdl-7621351

RESUMEN

Distal radius photodensitometric and second metacarpal radiogrammetric measurements were obtained from computerized analyses of standard hand X-Ray films of 296 Caucasian subjects (189 women and 107 men). This sample included 134 subjects > or = 65 years old (75 women and 59 men). Distal radius bone density and metacarpal index showed a significant linear decrease with age in both sexes. Rates of bone loss, calculated from the regression curves, were -0.7% per year in women and -0.5% per year in men by distal radial photodensitometry, and -0.49% per year in women and -0.33% per year in men by metacarpal radiogrammetry. In the elderly subgroup, women > or = 65 years of age showed an even faster bone loss, with an annual decrease of -1.4% by distal radial photodensitometry. Conversely, men > or = 65 years of age had no significant bone loss, not even by metacarpal radiogrammetry. In conclusion, these data suggest that appendicular cortical bone loss occurs at a higher rate in elderly females than in the elderly males, both at the distal radial and at the metacarpal site.


Asunto(s)
Anciano , Resorción Ósea/epidemiología , Osteoporosis/epidemiología , Diferenciación Sexual , Absorciometría de Fotón , Adulto , Factores de Edad , Densidad Ósea , Resorción Ósea/diagnóstico por imagen , Resorción Ósea/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Osteoporosis/diagnóstico por imagen , Osteoporosis/fisiopatología , Análisis de Regresión
15.
J Am Coll Cardiol ; 25(4): 871-8, 1995 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-7884090

RESUMEN

OBJECTIVES: We examined the prognostic significance of concentric remodeling of the left ventricle in patients with essential hypertension and normal left ventricular mass on echocardiography. BACKGROUND: An echocardiographic pattern of concentric remodeling of the left ventricle has been associated with clinical features of increased cardiovascular risk, but the independent prognostic value of this finding in hypertensive patients with normal left ventricular mass has not been established. METHODS: Six hundred ninety-four patients with essential hypertension and normal left ventricular mass (< 125 g/m2) on echocardiography were prospectively followed up for < or = 7.7 years (mean 2.71). Baseline echocardiography and 24-h noninvasive ambulatory blood pressure monitoring were performed in all patients at the time of initial diagnostic evaluation. Concentric remodeling was defined by the thickness of the septum or posterior wall divided by the left ventricular radius at end-diastole > or = 0.45. RESULTS: Prevalence of concentric remodeling was 39.2%. During follow-up there were 29 cardiovascular morbid events. Cardiovascular morbidity, expressed as the combined number of fatal and nonfatal events per 100 patient-years, was 1.53 in the overall study group, 1.12 in the subgroup with normal left ventricular geometry and 2.39 in that with concentric remodeling. After assessment of the independent association with several covariates (age, gender, diabetes, left ventricular mass index, mean clinic blood pressure and mean 24-h ambulatory blood pressure) in Cox proportional hazard models, the risk of cardiovascular morbid events was higher in the group with concentric remodeling than in that with normal geometry (relative risk 2.56, 95% confidence interval 1.20 to 5.45, p < 0.01). CONCLUSIONS: Concentric remodeling of the left ventricle, defined by the thickness of the septum or posterior wall divided by the left ventricular radius at end-diastole > or = 0.45, is an important and independent predictor of increased cardiovascular risk in hypertensive patients with normal left ventricular mass on echocardiography.


Asunto(s)
Ventrículos Cardíacos/diagnóstico por imagen , Hipertensión/diagnóstico por imagen , Adulto , Presión Sanguínea , Monitoreo Ambulatorio de la Presión Arterial , Distribución de Chi-Cuadrado , Ecocardiografía , Femenino , Estudios de Seguimiento , Humanos , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Función Ventricular Izquierda
16.
Dig Dis Sci ; 39(12): 2601-6, 1994 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-7995185

RESUMEN

In an attempt to obtain site-specific delivery of 5-ASA in the intestinal tract, we have determined the extent of absorption and metabolism of a number of novel 5-ASA derivatives, namely, (N-L-glutamyl)-amino-2-salicylic acid (1), (N-L-aspartyl)-amino-2-salicylic-acid (2), 5-aminosalicyl-L-proline-L-leucine (3), and 5-(N-L-glutamyl)-aminosalicyl-L-proline-L-leucine (4), which are selectively cleaved by intestinal brush border aminopeptidase A and carboxypeptidases. These novel prodrugs, 5-ASA, and sulfasalazine were administered to adult Fisher rats (N = 30) and to animals that had undergone prior colostomy (N = 30). Urine and feces were collected at timed intervals for 48 hr and the metabolites, 5-ASA, and N-acetyl-5-ASA were measured by high-performance liquid chromatography. The absorption and metabolism of all compounds were essentially identical in colostomized and normal animals. 5-ASA exhibited a rapid proximal intestinal absorption as evidenced by the high cumulative urinary excretion (> 65%) and low fecal excretion. Sulfasalazine, as expected, exhibited a lower urinary recovery (< 35%) and higher fecal excretion of 5-ASA and its metabolite. The novel glutamate and aspartate derivatives (1 and 2) behaved similarly to sulfasalazine, while administration of the proline-leucine derivative (3) resulted in urinary and fecal recovery values intermediate with respect to those observed with 5-ASA and sulfasalazine. 5-(N-L-Glutamyl)-aminosalicyl-L-proline-L-leucine yielded the highest fecal recovery of 5-ASA and its N-acetyl derivative, indicating a more efficient delivery to the distal bowel. Amino acid derivatives of 5-ASA appear to be potentially useful prodrugs for the site-specific delivery of 5-ASA to different regions of the intestinal tract.


Asunto(s)
Ácidos Aminosalicílicos/uso terapéutico , Profármacos/uso terapéutico , Aminopeptidasas/metabolismo , Ácidos Aminosalicílicos/administración & dosificación , Ácidos Aminosalicílicos/farmacocinética , Animales , Carboxipeptidasas/metabolismo , Cromatografía Líquida de Alta Presión , Colostomía , Glutamil Aminopeptidasa , Absorción Intestinal , Masculino , Mesalamina , Microvellosidades/enzimología , Ratas , Ratas Endogámicas , Sulfasalazina/farmacocinética , Sulfasalazina/uso terapéutico
17.
Hypertension ; 24(6): 793-801, 1994 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-7995639

RESUMEN

To determine the prognostic significance of ambulatory blood pressure, we prospectively followed for up to 7.5 years (mean, 3.2) 1187 subjects with essential hypertension and 205 healthy normotensive control subjects who had baseline off-therapy 24-hour noninvasive ambulatory blood pressure monitoring. Prevalence of white coat hypertension, defined by an average daytime ambulatory blood pressure lower than 131/86 mm Hg in women and 136/87 mm Hg in men in clinically hypertensive subjects, was 19.2%. Cardiovascular morbidity, expressed as the number of combined fatal and nonfatal cardiovascular events per 100 patient-years, was 0.47 in the normotensive group, 0.49 in the white coat hypertension group, 1.79 in dippers with ambulatory hypertension, and 4.99 in nondippers with ambulatory hypertension. After adjustment for traditional risk markers for cardiovascular disease, morbidity did not differ between the normotensive and white coat hypertension groups (P = .83). Compared with the white coat hypertension group, cardiovascular morbidity increased in ambulatory hypertension in dippers (relative risk, 3.70; 95% confidence interval, 1.13 to 12.5), with a further increase of morbidity in nondippers (relative risk, 6.26; 95% confidence interval, 1.92 to 20.32). After adjustment for age, sex, diabetes, and echocardiographic left ventricular hypertrophy (relative risk versus subjects with normal left ventricular mass, 1.82; 95% confidence interval, 1.02 to 3.22), cardiovascular morbidity in ambulatory hypertension was higher (P = .0002) in nondippers than in dippers in women (relative risk, 6.79; 95% confidence interval, 2.45 to 18.82) but not in men (P = .91). Our findings suggest that ambulatory blood pressures stratifies cardiovascular risk in essential hypertension independent of clinic blood pressure and other traditional risk markers including echocardiographic left ventricular hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)


Asunto(s)
Monitoreo Ambulatorio de la Presión Arterial , Hipertensión/fisiopatología , Adulto , Anciano , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/mortalidad , Ecocardiografía , Femenino , Predicción , Humanos , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Morbilidad , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Análisis de Supervivencia
18.
Diabetes ; 43(7): 920-8, 1994 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-8013758

RESUMEN

To establish the antihyperglycemic mechanisms of metformin in non-insulin-dependent diabetes mellitus (NIDDM) independently of the long-term, aspecific effects of removal of glucotoxicity, 21 NIDDM subjects (14 obese, 7 nonobese) were studied on two separate occasions, with an isoglycemic (plasma glucose approximately 9 mM) hyperinsulinemic (two-step insulin infusion, 2 h each, at the rate of 4 and 40 mU.m-2.min-1) clamp combined with [3-3H]glucose infusion and indirect calorimetry, after administration of either metformin (500 mg per os, at -5 and -1 h before the clamp) or placebo. Compared with placebo, hepatic glucose production (HGP) decreased approximately 30% more after metformin (from 469 +/- 50 to 330 +/- 54 mumol/min), but glucose uptake did not increase. Metformin suppressed free fatty acids (FFAs) by approximately 17% (from 0.42 +/- 0.04 to 0.35 +/- 0.04 mM) and lipid oxidation by approximately 25% (from 4.5 +/- 0.4 to 3.4 +/- 0.4 mumol.kg-1.min-1) and increased glucose oxidation by approximately 16% (from 16.2 +/- 1.4 to 19.3 +/- 1.3 mumol.kg-1.min-1) compared with placebo (P < 0.05), but did not affect nonoxidative glucose metabolism, protein oxidation, or total energy expenditure. Suppression of FFA and lipid oxidation after metformin correlated with suppression of HGP (r = 0.70 and r = 0.51, P < 0.001). The effects of metformin in obese and nonobese subjects were no different. We conclude that the specific, antihyperglycemic effects of metformin in the clinical condition of hyperglycemia in NIDDM are primarily due to suppression of HGP, not stimulation of glucose uptake, and are mediated, at least in part, by suppression of FFA and lipid oxidation.


Asunto(s)
Glucemia/efectos de los fármacos , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus/sangre , Glucosa/metabolismo , Hígado/metabolismo , Metformina/farmacología , Obesidad , Adulto , Glucemia/metabolismo , Índice de Masa Corporal , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/fisiopatología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/fisiopatología , Ácidos Grasos no Esterificados/sangre , Femenino , Gluconeogénesis/efectos de los fármacos , Técnica de Clampeo de la Glucosa , Hemoglobina Glucada/análisis , Humanos , Insulina/sangre , Hígado/efectos de los fármacos , Masculino , Metformina/uso terapéutico , Persona de Mediana Edad , Oxidación-Reducción
19.
Aging (Milano) ; 6(3): 201-7, 1994 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-7993928

RESUMEN

Both low and high platelet MAO-B (pMAO-B) activity is considered an indicator of increased vulnerability in psychopathology. How the activity of this peripheral enzyme can be linked with the sophisticated functions of the central nervous system (CNS) is not clear; in man, evidence exists that the genetic mechanisms determining the size or capacity of the central serotonin system are common to platelet and brain MAO. In the present study pMAO-B activity was evaluated in demented patients suffering from early-onset Alzheimer's disease (AD), late-onset Alzheimer's disease (SDAT), vascular dementia (VD), and controls. In these dementia categories, the relationship between pMAO-B activity and clinical features, and between pMAO-B activity and cerebrospinal fluid (CSF) monoamine metabolites (3-methoxy-4-hydroxyphenyl-glycol, MHPG; 5-hydroxy-indoleacetic acid, 5-HIAA; homovanillic acid, HVA) was also investigated. pMAO-B activity was significantly higher in SDAT patients, compared to controls and AD. Age, as covariate, failed to show any significant effect, and no association was found between pMAO-B activity and CSF monoamine metabolites. The correlation analysis between pMAO-B and neuropsychological scores showed a highly significant positive relationship with GBS-emotional impairment (N = 40, r = 0.72, p < 0.01) in the SDAT group. This result suggests the importance of platelet MAO-B activity as biological marker also in old-age dementias, namely senile dementia of Alzheimer type, where the increased activity of this enzyme might constitute a marker for vulnerability toward behavioural disturbance, i.e., emotional deterioration.


Asunto(s)
Síntomas Afectivos/diagnóstico , Enfermedad de Alzheimer/enzimología , Plaquetas/enzimología , Demencia Vascular/enzimología , Monoaminooxidasa/metabolismo , Síntomas Afectivos/etiología , Anciano , Envejecimiento/metabolismo , Enfermedad de Alzheimer/psicología , Biomarcadores/sangre , Biomarcadores/líquido cefalorraquídeo , Demencia Vascular/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Monoaminooxidasa/sangre , Monoaminooxidasa/líquido cefalorraquídeo
20.
Clin Exp Hypertens ; 15 Suppl 1: 39-54, 1993.
Artículo en Inglés | MEDLINE | ID: mdl-8513313

RESUMEN

1224 out-patients who consecutively underwent a Biosound examination of carotid arteries were retrospectively analyzed in order to estimate prevalence of carotid lesions and the role played by age, sex and major vascular risk factors with respect to carotid atherosclerosis. They were subdivided in asymptomatic and symptomatic subjects, making a distinction in both subgroups between patients with (RF+) or without (RF-) major vascular risk factors. Carotid lesions were present in 41% of asymptomatic RF- subjects; in 53% of asymptomatic RF+ subjects; in 53% of symptomatic RF- subjects and in 75% of symptomatic RF+ subjects. Carotid disease increases along with age, being more frequent in men than in women. The logistic regression model has then shown that increasing age, male gender, cigarette smoking and hyperlipidaemia are predictors of carotid atherosclerosis, while hypertension has been proved to play significant role only in the age class 61-69 yr.


Asunto(s)
Enfermedades de las Arterias Carótidas/etiología , Hipertensión/complicaciones , Arteriosclerosis Intracraneal/etiología , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Enfermedades de las Arterias Carótidas/epidemiología , Constricción Patológica , Complicaciones de la Diabetes , Femenino , Humanos , Hiperlipidemias/complicaciones , Arteriosclerosis Intracraneal/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Análisis de Regresión , Factores de Riesgo , Factores Sexuales , Fumar/efectos adversos
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