Metabolic syndrome as a predictor of all-cause and cardiovascular mortality in type 2 diabetes: the Casale Monferrato Study

OBJECTIVE: The aim of this study was to assess in an 11-year survival follow-up of a population-based cohort of type 2 diabetes the predictive role of World Health Organization-defined metabolic syndrome, independent of conventional cardiovascular risk factors. RESEARCH DESIGN AND METHODS: During the follow-up (1991-2001), 1,565 patients were regularly examined with centralized measurements of HbA(1c). The independent role of the metabolic syndrome as a predictor of all-cause and cardiovascular mortality was assessed with multivariate Cox proportional hazards modeling. RESULTS: At baseline, the prevalence of the metabolic syndrome was 75.6% (95% CI 73.6-77.9). Results are based on 685 deaths (520 with the metabolic syndrome and 165 without it) in 10,890.2 person-years of observations. With respect to subjects without the metabolic syndrome, those with the metabolic syndrome had a similar hazard ratio (HR) of cardiovascular mortality after adjustment for age, sex, smoking, total cholesterol level, and coronary heart disease. In contrast, relative to subjects with diabetes only, the HR of subjects with only one component of the syndrome was 2.92 (1.16-7.33), independent of other risk factors. CONCLUSIONS: We found that 1) the prevalence of the metabolic syndrome in a population-based cohort of type 2 diabetes is high (75.6%); 2) the metabolic syndrome is not a predictor of 11-year all-cause and cardiovascular mortality; and 3) more than twofold higher cardiovascular risk, independent of conventional risk factors, is evident in diabetic subjects with only one component of the syndrome compared with those with diabetes only. Categorizing type 2 diabetic subjects as having or not having the metabolic syndrome does not provide further prediction compared with the knowledge of its single components.     

Polymorphisms in the pertussis toxin promoter in Bordetella bronchiseptica veterinary isolates from Argentina

Five restriction patterns (including a novel one) could be defined by polymerase chain reaction-restriction fragment length polymorphism on the pertussis toxin (PT) promoter region in local veterinary isolates, suggesting that PT gene analysis is a potential molecular marker for Bordetella bronchiseptica detection and typing.     

Short-term effects of weight loss on the cardiovascular risk factors in morbidly obese patients

OBJECTIVE: To analyze the short-term effects of weight loss on the cardiovascular risk factors in morbidly obese patients. RESEARCH METHODS AND PROCEDURES: Five metabolic cardiovascular risk factors (blood glucose, blood pressure, total cholesterol, high-density lipoprotein (HDL)-cholesterol, and triglycerides) were determined before and 15.3 +/- 2.1 months after laparoscopic gastric banding in 650 morbidly obese patients. Global cardiovascular risk was calculated according to the Prospective Cardiovascular Münster (PROCAM) scoring system. RESULTS: Mean weight loss was 22.7 +/- 20.4 kg. Normalization of the metabolic alteration was observed in 67.3% of patients with diabetes, 38.3% of patients with hypercholesterolemia, 72.5% of patients with low HDL-cholesterol, 72.3% of patients with hypertriglyceridemia, and 46.7% of patients with hypertension. PROCAM score fell from 31.4 +/- 11.6 to 28.0 +/- 12.0 points (p < 0.001). The modifications of total cholesterol and blood pressure were unrelated to percentage weight loss. Percentage weight loss was significantly related to the reductions of fasting blood glucose, triglyceride level, and the PROCAM score and to the increase of HDL-cholesterol concentrations observed after surgery. However, the strength of these four relationships was generally low. The variations of HDL-cholesterol concentrations and blood pressure levels were more influenced by actual energy balance than by the extent of weight loss. DISCUSSION: Weight loss observed in the first 12 to 18 months after gastric banding was associated with a significant improvement of single cardiovascular risk factors and global risk. On the other hand, the extent of weight loss was poorly related to the magnitude of improvement in cardiovascular risk.     

Which patients with prostate cancer are actually candidates for hormone therapy?

In this article, we will try to address the following aspects: which factors are responsible of the introduction of new candidates for hormone therapy in prostate cancer, who are actually candidates for hormone therapy, classifying them on the basis of the stage of the disease, and which treatment modalities can be proposed for each candidate. Since the introduction of hormone therapy for the treatment of prostate cancer, there has been a debate about the optimal timing of hormone therapy. A modification in the timing of hormone therapy produced new candidates for hormone manipulation. In particular, the use of hormone treatment for younger patients, longer periods and early prostate cancer, absolutely requires a whole re-evaluation of which therapy is indicated and it may produce new problems such as higher risk of over-treatment, need of a better evaluation of quality of life in younger patients and the research for better tolerated therapies. Therapies that resist for longer periods without the production of a hormone-refractory disease are also required.     

Health policy and occupational health: tools and methods to assure quality and appropriateness of interventions

BACKGROUND: Although all health care organizations and professionals are encouraged to follow the explicit aim of reducing the burden of illness, accidents and disability, there is increasing pressure on health professionals to ensure that the practice be based on a quality standard and on evidence of appropriateness. OBJECTIVES AND METHODS: The paper aims to focus on both the concept and dimensions of appropriateness (a complex issue with various dimensions and definitions) and on the different research and practice models aimed at search, analysis and synthesis of the best available evidence to be applied in the decision process of health and medical practice. Literature analysis has been carried out to find available tools and methods to identify, implement and monitor the evidence of efficacy in health care systems and services. RESULTS: Most definitions of appropriateness address a number of requirements. An appropriate practice should be effective (based on sound evidence); efficient (providing that cost is considered) and consistent with the ethical principles and preferences of the relevant individual, community or society. Appropriateness is considered as the next frontier in the development of health care research: there is still limited knowledge, awareness, or research on this aspect. Health Technology Assessment consists of a multidisciplinary activity based on the systematic examination of technical performance, safety, clinical effectiveness and efficiency, including socio-economic, legal and ethical aspects. Evidence Based Medicine originates from an individual perspective and aims at using rigorous criteria to obtain the best available evidence in order to provide efficient interventions. The Clinical Practice Guidelines, based on both evidence and opinions of experts, are intended to assist clinical decisions for health professional and providers for the improvement of professional practices and system efficiency, taking into account local customers, health needs and preferences. CONCLUSIONS: Several models exist for measuring and evaluating the efficacy of health systems and health services. They can be adapted for evaluating and measuring public and occupational health practices. These tools support good practice through quality-standardized interventions aiming at the health protection of communities and individuals. These models, which are presented in a specific framework in which their outcomes and critical factors are evaluated, should be adapted to public and occupational health interventions to satisfy implicit and explicit needs of individuals and populations at risk thus assuring their quality and appropriateness.     

Tricyclic alkylamides as melatonin receptor ligands with antagonist or inverse agonist activity

This work reports the design and synthesis of novel alkylamides, characterized by a dibenzo[a,d]cycloheptene nucleus, as melatonin (MLT) receptor ligands. The tricyclic scaffold was chosen on the basis of previous quantitative structure-activity studies on MT1 and MT2 antagonists, relating selective MT2 antagonism to the presence of an aromatic substituent out of the plane of the MLT indole ring. Some dibenzo seven-membered structures were thus selected because of the noncoplanar arrangement of their benzene rings, and an alkylamide chain was introduced to fit the requirements for MLT receptor binding, namely, dibenzocycloheptenes with an acylaminoalkyl side chain at position 10 and dibenzoazepines with this side chain originating from the nitrogen atom bridging the two phenyl rings. Binding affinity at human cloned MT1 and MT2 receptors was measured by 2-[125I]iodomelatonin displacement assay and intrinsic activity by the GTPgammaS test. The majority of the compounds were characterized by higher affinity at the MT2 than at the MT1 receptor and by very low intrinsic activity values, thus confirming the importance of the noncoplanar arrangement of the two aromatic rings for selective MT2 antagonism. Dibenzocycloheptenes generally displayed higher MT1 and MT 2affinity than dibenzoazepines. N-(8-Methoxy-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-10-ylmethyl)propionamide (4c) and -butyramide (4d) were the most selective MT2 receptor antagonists of the series, with MT2 receptor affinity comparable to that of melatonin and as such among the highest reported in the literature for MLT receptor antagonists. The acetamide derivative 4b produced a noticeable reduction of GTPgammaS binding at MT2 receptor, thus being among the few inverse agonists described.