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Buenos Aires, Argentina

Despite the increasing prevalence and the potential benefits of early identification, dementias continue to be under-diagnosed. By some estimates, fewer than half of all dementia patients have been diagnosed. AD is particularly under-diagnosed in primary care settings perhaps because patients with early AD may appear entirely appropriate in the context of a brief office visit. This, coupled with increasingly abbreviated office visits and the lack of routine use of mental status exams, make identification of cognitive deficit challenging in the primary care setting. Detection of these patients must be made by the general practitioners, who must know the possibilities to detect and guide the study of them. Patients' screening must include discrimination of forgetfulness and use of mini mental examination. Once the cognitive impairment is suspected we need to continue with neuropsychological assessment for cognitive profile, ancillary studies and CT scan to exclude structural diseases. The appropriate knowledge and training of general practitioners will allow the early diagnosis of these patients and the beginning of preventive actions and adequate symptomatic treatment.

Gonzalez C.D.,CEMIC University Institute | Di Girolamo G.,University of Buenos Aires | Di Girolamo G.,Favaloro University
Current Drug Safety | Year: 2010

QT interval prolongation is one of the most important causes of withdrawal of drugs from the market, due to its association with Torsades de Pointes (TdP), a potentially fatal arrhythmia. Although many antimicrobial drugs are capable of inducing this type of arrhythmia, the importance of this effect is usually underestimated. Macrolides, quinolones, azoles, pentamidine, protease inhibitors, antimalarial drugs and cotrimoxazole are the anti-infective agents more frequently associated with this adverse effect. Despite the fact that the risk of QT prolongation and TdP under single antimicrobial therapy is low, these drugs are so extensively used that sporadic cases of this arrhythmia are reported. Moreover, antimicrobial drugs are susceptible to pharmacokinetic and pharmacodynamic interactions with other drugs, which may increase the risk of this arrhythmia. Therefore, physicians must be familiar with not only the antimicrobial drugs capable of producing QT interval prolongation, but also their potential interactions. In addition, patient's specific risk factors of prolonging QT interval or producing TdP must be taken into account. This article reviews the role of anti-infective drugs in QT prolongation, focusing on QT prolongation mechanisms, potential drug interactions, and patients' predisposing factors to this arrhythmia. © 2010 Bentham Science Publishers Ltd.

Orioli I.M.,Federal University of Rio de Janeiro | Castilla E.E.,Brazilian National Council for Scientific and Technological Development | Castilla E.E.,Laboratory of Congenital Malformations at the Instituto Oswaldo Cruz | Castilla E.E.,CEMIC University Institute
American Journal of Medical Genetics, Part C: Seminars in Medical Genetics | Year: 2010

The wide variation in cerebral and facial phenotypes and the recognized etiologic heterogeneity of holoprosencephaly (HPE) contribute to the observed inter-study heterogeneity. High lethality during the early stages of embryonic and fetal development makes HPE detection age dependent. By reviewing 21 HPE epidemiologic articles, the observed prevalence rate differences can be largely explained by the pregnancy outcome status of the studied cohort: livebirth, stillbirth, and terminations of pregnancy (TOPs): lower than 1 per 10,000 when live and still births were included, higher when TOPs were included, and between 40 and 50 per 10,000 in two classical Japanese studies on aborted embryos. The increasing secular trend observed in some studies probably resulted from an increasing use of prenatal sonography. Ethnic variations in birth prevalence rates (BPRs) could occur in HPE, but the available data are not very convincing. Higher BPRs were generally observed in the less favored minorities (Blacks, Hispanics, Pakistanis), suggesting a bias caused by a lower prenatal detection rate of HPE, and consequently less TOPs. Severe ear defects, as well as microstomia, were part of the spectrum of HPE. Non-craniofacial anomalies, more frequently associated with HPE than expected, were genital anomalies (24%), postaxial polydactyly (8%), vertebral defects (5%), limb reduction defects (4%), and transposition of great arteries (4%). The variable female predominance, found in different HPE studies, could also depend on the proportion of early conceptions in each study sample, as males are more likely to be lost through spontaneous abortions. © 2010 Wiley-Liss, Inc.

Giorgi M.A.,National Academy of Medicine | Bolanos R.,University of Buenos Aires | GonzaleZ. C.D.,CEMIC University Institute | Di Girolamo G.,University of Buenos Aires | Di Girolamo G.,Favaloro University
Current Drug Safety | Year: 2010

The assessment about the proarrhythmic risk associated with a particular drug is a major requirement for drugs under development, since many drugs have been withdrawn from market or got under strict pharmacological vigilance because of such a risk. Predicting the development of a life-threatening arrhythmia is a hard task but, in the case of TdP ("Torsades de Pointes"), there are some useful markers. Among them, the prolongation of the QT interval and its heart rate correction (QTc) are the most remarkable. Actually, QT prolongation is considered the surrogate marker of TdP from the clinical and regulatory standpoint. ICH E14 provides recommendations to sponsors concerning the design, conduct, analysis, and interpretation of clinical studies to assess the potential of a drug to delay cardiac repolarization. The regulatory information about preclinical safety evaluation is contained in ICH S7B. Both guidelines have been a matter of intense debate. False negative and false positive results have been found within the preclinical and clinical field. There still are grey areas in which further research would be necessary. Improvement of tools that may contribute to complement the data from the human ether-a-go-go-related gene HERG channel and QT/QTc studies, such as concentration-QT relationship (CQT) studies and other innovative techniques, will be more than welcome. © 2010 Bentham Science Publishers Ltd.

Catoira N.P.,University of Buenos Aires | Viale L.,University of Buenos Aires | Di Girolamo G.,University of Buenos Aires | Gonzalez C.,CEMIC University Institute
Current Medical Research and Opinion | Year: 2014

Background: Obesity is one of the major problems of health policy in different countries. Pharmacological attempts have been made to help affected people without a definitive solution. Some agents-either with peripheral or central effect-Are available in the market. On July 2012, the FDA approved two novel preparations for obese patients: (1) topiramate-phentermine-The first one an anticonvulsant and the second one a sympathomimetic amine-And (2) lorcaserin, a 5-HT2CR agonist. Both preparations emerged as new options for weight management. Scope: Based on the complex biology of eating behavior, in this review we discuss the features, mechanisms of action, pharmacokinetics, advantages and possible disadvantages of these new agents. Conclusion: With differences in efficacy (higher for the topiramate-phentermine combination), both preparations are active in reducing appetite and body weight, as well as in improving comorbidities. Additional information will be collected from Phase IV surveillance. Focus on cardiovascular, neuropsychiatric (for both introductions) and embrio-fetal safety (especially for topiramate) is expected. © 2014 2014 Informa UK Ltd.

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