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PubMed | Hospital Privado, Hospital Of Especialidades Centro Medico Nacional Siglo Xxi, University of Santiago de Chile, Federal University of Rio Grande do Sul and 10 more.
Type: Comparative Study | Journal: Lupus | Year: 2015

To examine the characteristics of patients who developed late onset systemic lupus erythematosus (SLE) in the GLADEL (Grupo Latino Americano de Estudio del Lupus) cohort of patients with SLE.Patients with SLE of less than two years of disease duration, seen at 34 centers of nine Latin American countries, were included. Late-onset was defined as >50 years of age at time of first SLE-related symptom. Clinical and laboratory manifestations, activity index (SLEDAI), and damage index (SLICC/ACR- DI) were ascertained at time of entry and during the course (cumulative incidence). Features were compared between the two patient groups (<50 and 50) using descriptive statistics and hypothesis tests. Logistic regression was performed to examine the association of late-onset lupus, adjusting for other variables.Of the 1480 patients included, 102 patients (6.9 %) had late-onset SLE, 87% of which were female. Patients with late-onset SLE had a shorter follow-up (3.6 vs. 4.4 years, p<0.002) and a longer time to diagnosis (10.1 vs. 5.8 months, p<0.001) compared to the younger onset group. Malar rash, photosensitivity, and renal involvement were less prevalent while interstitial lung disease, pleural effusions, and sicca symptoms were more frequent in the older age group (p>0.05). In multivariable analysis, late onset was independently associated with higher odds of ocular (OR=3.66, 95% CI=2.15-6.23), pulmonary (OR=2.04, 95% CI=1.01-4.11), and cardiovascular (OR=1.76, 95% CI=1.04-2.98) involvement and lower odds of cutaneous involvement (OR=0.41, 95% CI=0.21-0.80), number of cumulative SLE criteria (OR=0.79, 95% CI=0.64-0.97), use of cyclophosphamide (OR=0.47, 95% CI=0.24-0.95), and anti-RNP antibodies (OR=0.43, 95% CI=0.20-0.91). A Cox regression model revealed a higher risk of dying in older onset than the younger-onset SLE (OR=2.61, 95% CI=1.2-5.6).Late-onset SLE in Latin Americans had a distinct disease expression compared to the younger-onset group. The disease seems to be mild with lower cumulative SLE criteria, reduced renal/mucocutaneous involvements, and less use of cyclophosphamide. Nevertheless, these patients have a higher risk of death and of ocular, pulmonary, and cardiovascular involvements.


Jaimes N.,Sloan Kettering Cancer Center | Dusza S.W.,Sloan Kettering Cancer Center | Quigley E.A.,Sloan Kettering Cancer Center | Braun R.P.,University of Zürich | And 15 more authors.
Australasian Journal of Dermatology | Year: 2013

Background/Objectives Dermoscopy aids in clinical decision-making. However, time pressure is a common reason precluding its use. We evaluated the effect of time on lesion recognition and management decisions utilising clinical and dermoscopic images. Method In all, 100 dermoscopic images were presented to 15 dermatologists with experience in dermoscopy and seven non-experts (dermatology residents). Each lesion was displayed thrice in succession. The dermoscopic image was initially presented for 1 s (t1). The same dermoscopic image was shown again without time constraints (t2) and then a final time with additional images of the clinical context (t3). Participants provided a diagnosis, their level of confidence and biopsy predilection after evaluating each image. Results For benign lesions, both groups rarely changed their diagnosis. However, an improvement in the number of correct benign diagnoses was observed when the lesion was shown in a clinical context. For malignant lesions, both groups improved when more time and clinical context was given; nevertheless, non-experts were more likely to change the diagnosis towards the correct one as more time was given and tended to perform more biopsies, in particular of benign lesions. Limitations were a small number of participants and an artificial study setting. Conclusion Dermoscopy uses analytical and non-analytical reasoning approaches. We suggest that non-analytical reasoning is employed when rapid clinical decisions need to be made, especially during the evaluation of benign lesions. We conclude that dermoscopy is relatively rapid and non-time-consuming technique that adds relevant information and guides clinicians towards appropriate management decisions. © 2012 The Authors. Australasian Journal of Dermatology © 2012 The Australasian College of Dermatologists.


Pereira C.A.,Institute Investigaciones Medicas Alfredo Lanari | Silber A.M.,University of Sao Paulo
PLoS ONE | Year: 2012

Glucose, an almost universally used energy and carbon source, is processed through several well-known metabolic pathways, primarily glycolysis. Glucose uptake is considered to be the first step in glycolysis. In kinetoplastids, a protozoan group that includes relevant human pathogens, the importance of glucose uptake in different phases of the life cycles is well established, and hexose transporters have been proposed as targets for therapeutic drugs. However, little is known about the evolutionary history of these hexose transporters. Hexose transporters contain an intracellular N- and C- termini, and 12 transmembrane spans connected by alternate intracellular and extracellular loops. In the present work we tested the hypothesis that the evolutionary rate of the transmembrane span is different from that of the whole sequence and that it is possible to define evolutionary units inside the sequence. The phylogeny of whole molecules was compared to that of their transmembrane spans and the loops connecting the transmembrane spans. We show that the evolutionary units in these proteins primarily consist of clustered rather than individual transmembrane spans. These analyses demonstrate that there are evolutionary constraints on the organization of these proteins; more specifically, the order of the transmembrane spans along the protein is highly conserved. Finally, we defined a signature sequence for the identification of kinetoplastid hexose transporters. © 2012 Pereira, Silber.


Finkelsztejn A.,University of Caxias do Sul | Gabbai A.A.,Federal University of São Paulo | Fragoso Y.D.,Metropolitan University of Santos | Carra A.,Hospital Britanico | And 7 more authors.
Arquivos de Neuro-Psiquiatria | Year: 2012

Objective: It is estimated that circa 50,000 individuals have relapsing-remitting multiple sclerosis in Latin America. European and NorthAmerican algorithms for the treatment of multiple sclerosis do not foresee our regional difficulties and the access of patients to treatment. Methods: The Latin American Multiple Sclerosis Forum is an independent and supra-institutional group of experts that has assessed the latest scientific evidence regarding efficacy and safety of disease-modifying treatments. Accesses to treatment and pharmacovigilance programs for each of the eight countries represented at the Forum were also analyzed. Results: A specific set of guidelines based upon evidence-based recommendations was designed for Latin America. Future perspectives of multiple sclerosis treatment were also discussed. Conclusions: The present paper translated an effort from representatives of eight countries discussing a matter that cannot be adapted to our region directly from purely European and North-American guidelines for treatment.


Inbar E.,Technion - Israel Institute of Technology | Canepa G.E.,Institute Investigaciones Medicas Alfredo Lanari | Carrillo C.,University of Buenos Aires | Glaser F.,Technion - Israel Institute of Technology | And 4 more authors.
Amino Acids | Year: 2012

In previous studies we characterized arginine transporter genes from Trypanosoma cruzi and Leishmania donovani, the etiological agents of chagas disease and kala azar, respectively, both fatal diseases in humans. Unlike arginine transporters in higher eukaryotes that transport also lysine, these parasite transporters translocate only arginine. This phenomenon prompted us to identify and characterize parasite lysine transporters. Here we demonstrate that LdAAP7 and TcAAP7 encode lysine-specific permeases in L. donovani and T. cruzi, respectively. These two lysine permeases are both members of the large amino acid/auxin permease family and share certain biochemical properties, such as specificity and Km. However, we evidence that LdAAP7 and TcAAP7 differ in their regulation and localization, such differences are likely a reflection of the dissimilar L. donovani and T. cruzi life cycles. Failed attempts to delete both alleles of LdAAP7 support the premise that this is an essential gene that encodes the only lysine permeases expressed in L. donovani promastigotes and T. cruzi epimastigotes, respectively. © Springer-Verlag 2010.


Rabadan A.T.,Institute Investigaciones Medicas Alfredo Lanari | Sposato L.,Institute Neurociencias Of La Fundacion Favaloro | Mazia C.,Institute Investigaciones Medicas Alfredo Lanari
Medicina | Year: 2010

New options have been developed for the prevention and treatment of acute ischemic stroke in the last 20 years, such as carotid endarterectomy and intravenous thrombolysis with tissue plasminogen activator. Scientific evidence has supported their use in developed countries, while there is an evident delay in their use among emerging countries. Other promising modalities require the conclusion of ongoing randomized, controlled trials. Malignant middle or carotid cerebral artery infarction accounts for 10 to 15% ischemic strokes and constitutes a devastating event associated with high morbidity and mortality. Decompressive craniectomy seems to be an effective and safe approach for rapidly lowering intracranial pressure. Although randomized trials are lacking, there is enough evidence to support this surgical procedure in appropriately selected patients.


Zucchini A.E.,Institute Investigaciones Medicas Alfredo Lanari
Salud(i)Ciencia | Year: 2010

Ageing is accompanied by a decline in the physiological functional capacity, led by structural and functional changes in the arterial walls. At renal level, those alterations may result in glomerulosclerosis, loss of functioning nephrons and reduced glomerular filtration. These changes are not uniform in all human beings, as genetic predisposition and exposure to cardiovascular risk factors play a significant part in their development. The definition of chronic kidney disease (CKD) includes the presence of albuminuria, and the estimation of the renal function via formulas such as Crockoft-Gault or MDRD, inadvertently result in an exaggerated prevalence of CKD among the over 65s. The mere deterioration of the renal function, in the absence of progressive cardiovascular or other related diseases is not clinically significant; however, there may exist defective water and electrolyte management, increased sensitivity to volumetric changes and to the effects of several drugs. The incidence of primary kidney diseases is similar to that observed in young populations, the exception being the occurrence of light chain excretions, myelomas and amylodosis. CKD prevalence in the over 70s climbed to 48% according to the NAHNES III study. In Argentina, 24.6% of dialysis admissions are aged between 75 and 79. Active policy measures are required in order to improve the renal health care of the elderly. Copyrigth © Sociedad Iberoamericana de Información Científica (SIIC), 2010.


PubMed | Institute Investigaciones Medicas Alfredo Lanari
Type: Case Reports | Journal: Medicina | Year: 2011

Meningeal involvement is an infrequent manifestation of Wegeners granulomatosis. Clinical manifestations can be headache with high protein level in the cerebrospinal fluid and an enhanced MRI signal of granulomatous thickening of the duramater in the brain. We report a 57 year-old male with Wegener granulomatosis with onset manifestations of asymptomatic granulomatous meningitis, upper respiratory tract, ears and orbits involvement. He progressively developed ANCA positive multiple mononeuritis and crescentic glomerulonephritis. The diagnostic confirmation of Wegeners granulomatosis based on a positive ANCA test and on the evidence of systemic disease (crescentic glomerulonephritis and involvement of the upper respiratory tract, ears, orbits, peripheral nerves and duramater) allowed a prompt initiation of aggressive immunosuppressive treatment with systemic cyclophosphamide and high - dosis corticosteroids. The patient entered into a sustained clinical remission with mild residual neurosensorial hearing loss and renal failure.


PubMed | Institute Investigaciones Medicas Alfredo Lanari
Type: Journal Article | Journal: PloS one | Year: 2012

Glucose, an almost universally used energy and carbon source, is processed through several well-known metabolic pathways, primarily glycolysis. Glucose uptake is considered to be the first step in glycolysis. In kinetoplastids, a protozoan group that includes relevant human pathogens, the importance of glucose uptake in different phases of the life cycles is well established, and hexose transporters have been proposed as targets for therapeutic drugs. However, little is known about the evolutionary history of these hexose transporters. Hexose transporters contain an intracellular N- and C- termini, and 12 transmembrane spans connected by alternate intracellular and extracellular loops. In the present work we tested the hypothesis that the evolutionary rate of the transmembrane span is different from that of the whole sequence and that it is possible to define evolutionary units inside the sequence. The phylogeny of whole molecules was compared to that of their transmembrane spans and the loops connecting the transmembrane spans. We show that the evolutionary units in these proteins primarily consist of clustered rather than individual transmembrane spans. These analyses demonstrate that there are evolutionary constraints on the organization of these proteins; more specifically, the order of the transmembrane spans along the protein is highly conserved. Finally, we defined a signature sequence for the identification of kinetoplastid hexose transporters.


PubMed | Institute Investigaciones Medicas Alfredo Lanari
Type: Journal Article | Journal: Medicina | Year: 2012

The mammalian TOR pathway (Target Of Rapamycin) is a regulatory protein network involved in a wide range of processes including cell growth and differentiation, providing a functional switch between anabolic and catabolic cell metabolism. Trypanosoma cruzi, the etiologic agent of Chagas disease, has a complex life cycle with different morphological stages in various hosts. This life cycle implies that parasites have to deal with fluctuations in the extracellular medium that should be detected and counteracted adapting their metabolism. A candidate to be the mediator between the receptors / sensors of the environment and cellular adaptive response is the TOR pathway. In this paper we integrate the bibliographic data of the TOR pathway in trypanosomatids by in silico analysis (computer simulation of biological structures and processes) of the parasites genome. Possible effectors and processes regulated by this metabolic pathway are also proposed. Given that the information on the mechanisms of signal transduction in trypanosomatids is scarce, we consider the model presented in this work may be a reference for future experimental work.

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