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CEMIC University Institute

Buenos Aires, Argentina
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Petracchi F.,CEMIC University Institute | Paez C.,CEMIC University Institute | Igarzabal L.,CEMIC University Institute
Prenatal Diagnosis | Year: 2017

Objective: To compare the cost-effectiveness of performing chorionic villus sampling (CVS) of products of conception (POC) in the evaluation of recurrent miscarriage versus standard evidence-based work-up (EBW) of the couple. Material and methods: A decision-analytic model was performed in couples with a third miscarriage. Three strategies were considered: (1) the standard EBW of all the patients, comprising parental karyotype, uterine cavity assessment and antiphospholipid antibodies; (2) performing a CVS of POC and a standard karyotype, and if euploid, follow with EBW; and (3) performing a CVS of POC and an arrayCGH and, if normal, follow with EBW. Estimated cost and diagnostic yield of each strategy was analysed. Sensitivity analysis and threshold cost were considered. Results: The expected cost-effectiveness of CVS and karyotype of POC in recurrent miscarriage was: $US769.79 versus $US 1361.8 for the standard EBW of the couple. When stratified by maternal age the results remained cost-effective for this strategy. The arrayCGH strategy has a higher diagnostic yield, but still expensive in our setting to be considered cost-effective. Conclusions: Chorionic villus sampling and karyotype analysis of products of conception in a third miscarriage proved a more cost-effective strategy than standard EBW of the couple. © 2017 John Wiley & Sons, Ltd.

Mengoni E.S.,CONICET | Vichera G.,CONICET | Rigano L.A.,CONICET | Rodriguez-Puebla M.L.,North Carolina State University | And 5 more authors.
Fitoterapia | Year: 2011

In the present study, we evaluated the effects of extracts and purified compounds from fresh leaves of Rosmarinus officinalis L. Pretreatment with the major anti-inflammatory compounds, carnosic acid (CA) and carnosol (CS), inhibited phorbol 12-myristate 13-acetate (PMA)-induced ear inflammation in mice with an EC50 of 10.20 μg/cm2 and 10.70 μg/cm 2, respectively. To further understand the anti-inflammatory mechanism of these compounds, we analyzed the in vivo expression of several inflammation-associated genes in mouse skin by reverse transcriptase-polymerase chain reaction (RT-PCR). Our data showed that CA and CS reduced the expression of IL-1β and TNF-α but had less effect on fibronectin and ICAM-1 expression. Interestingly, both compounds selectively inhibited COX-2 but not COX-1. Histopathological analysis of hematoxylin and eosin (H&E)-stained tissue revealed a marked reduction in leukocyte infiltration and epidermal ulceration of PMA-treated ears when ears were pretreated with ethanolic extracts or pure CA. In vitro, we showed that ethanolic extract, carnosic acid and carnosol significantly inhibited the overproduction of nitric oxide (NO) in a dose-dependent manner in the RAW 264.7 murine macrophage cell line. For the first time in vivo, we showed that CA and CS differentially regulate the expression of inflammation-associated genes, thus demonstrating the pharmacological basis for the anti-inflammatory properties reported for CA and CS. © 2010 Elsevier B.V. All rights reserved.

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.

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.

Petracchi F.,CEMIC University Institute | Crespo L.,CEMIC University Institute | Michia C.,CEMIC University Institute | Igarzabal L.,CEMIC University Institute | Gadow E.,CEMIC University Institute
Prenatal Diagnosis | Year: 2011

Objective: To assess the likelihood of finding an etiopathogenic cause in an ultrasonographic prenatal diagnosis of holoprosencephaly. Materials and Methods: From January 1996 to June 2010, 13 883 prenatal diagnoses through chorionic villus sampling or amniocentesis were made. Every fetus with holoprosencephaly at ultrasound was evaluated. Gestational age, additional ultrasound findings, and fetal karyotype were recorded. Molecular diagnosis and parental karyotype were studied, if relevant. Results: Twenty-eight fetuses were diagnosed with holoprosencephaly (0.20%). All cases had additional ultrasound findings (100%). A definitive etiology was found in 23 cases (82.14%): karyotype was abnormal in 19 (67.9%) and normal in 8 (28.5%) cases. In the normal karyotype group, although molecular testing was performed in a few cases, one mutation of gene SIX 3 was diagnosed, one diagnosis of dysgnathia complex was made, and two fetuses presented Smith-Lemli-Opitz syndrome. No etiopathogenic diagnosis was made in five fetuses. Conclusions: Our results showed that a definitive etiology can be established in most cases of prenatal holoprosencephaly. Chromosomal anomalies were the most frequent finding. However, in euploid fetuses, molecular diagnosis is worthwhile, as different genes with different inheritance patterns may be responsible for this malformation. Thorough evaluation proved beneficial for assessing more accurate prognosis and recurrence risks. © 2011 John Wiley & Sons, Ltd.

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.

Introduction. Patients with intestinal bacterial overgrowth (SIBO) are usually treated with different antibiotics. Certain probiotics have proved to be clinically effective in patients with abdominal distension. Objective. To compare the short-term clinical efficacy of metronidazol vs a probiotic in patients with SIBO and functional chronic abdominal distension. Patients and methods. This was a randomized prospective pilot study. The study population consisted of 50 patients with chronic abdominal distension (Rome III criteria) and diagnosis of SIBO made by a lactulose H2 breath test. Patients were consecutively randomized to receive either metronidazol or a probiotic. The metronidazol group consisted of 25 subjects (23 women, median age 49±19 years old), who received metronidazol (Flagyl ®), 500 mg bid for 5 days. The probiotic group consisted of 25 subjects (20 women, median age 58±19 years old). The probiotic administered to the latter group contained Lactobacillus casei (3.3 × 107 UFC), Lactobacillus plantarum (3.3 × 107 UFC), Streptococcus faecalis (3.3 × 10 7 UFC) and Bifidobacterium brevis (1.0 × 106 UFC) (Bioflora ®) and 5ml bid were administered for 5 days. Both groups went on the same diet, which consisted in reduced consumption of alcohol, legumes, dairy products and leafy green vegetables. Response to treatment was assessed by an independent questioner 15 days post treatment. A five-level overall response questionnaire was used. Responses included much better, better, the same, worse, and much worse. Better and much better were considered positive responses. Results. Thirteen (52%) subjects receiving metronidazol and 20 (82%) receiving the probiotic referred clinical improvement after the treatment. A statistically significant difference favoured the use of the probiotic (P = 0.036). All the study patients completed treatment. No adverse events leading to treatment discontinuation were observed. Conclusions. Based on this pilot study results, we can suggest that the probiotic herein used has a higher efficacy than metronidazol in the early clinical response of patients with chronic abdominal distension and SIBO.

Castro D.M.,CEMIC University Institute | Dillon C.,Hospital General Abel Zubizarreta | MacHnicki G.,Hospital General Abel Zubizarreta | Allegri R.F.,CEMIC University Institute
Dementia e Neuropsychologia | Year: 2010

Alzheimer's disease (AD) patients suffer progressive cognitive, behavioral and functional impairment which result in a heavy burden to patients, families, and the public-health system. AD entails both direct and indirect costs. Indirect costs (such as loss or reduction of income by the patient or family members) are the most important costs in early and community-dwelling AD patients. Direct costs (such as medical treatment or social services) increase when the disorder progresses, and the patient is institutionalized or a formal caregiver is required. Drug therapies represent an increase in direct cost but can reduce some other direct or indirect costs involved. Several studies have projected overall savings to society when using drug therapies and all relevant cost are considered, where results depend on specific patient and care setting characteristics. Dementia should be the focus of analysis when public health policies are being devised. South American countries should strengthen their policy and planning capabilities by gathering more local evidence about the burden of AD and how it can be shaped by treatment options.

Dillon C.,CEMIC University Institute | Serrano C.M.,CEMIC University Institute | Castro D.,CEMIC University Institute | Leguizamon P.P.,CEMIC University Institute | And 3 more authors.
Neuropsychiatric Disease and Treatment | Year: 2013

Neuropsychiatric symptoms (NPS) are core features of Alzheimer's disease and related dementias. On one hand, behavioral symptoms in patients with mild cognitive impairment (MCI) can indicate an increased risk of progressing to dementia. On the other hand, mild behavioral impairment (MBI) in patients who usually have normal cognition indicates an increased risk of developing dementia. Whatever the cause, all dementias carry a high rate of NPI. These symptoms can be observed at any stage of the disease, may fluctuate over its course, are a leading cause of stress and overload for caregivers, and increase rates of hospitalization and early institutionalization for patients with dementia. The clinician should be able to promptly recognize NPI through the use of instruments capable of measuring their frequency and severity to support diagnosis, and to help monitor the treatment of behavioral symptoms. The aims of this review are to describe and update the construct 'MBI' and to revise the reported NPS related to prodromal stages of dementia (MCI and MBI) and dementia stages of Alzheimer's disease and frontotemporal lobar degeneration. © 2013 Dillon et al. This work is published by Dove Medical Press Ltd.

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