Papers by Guillermo Izquierdo
Ann Neurol, 2001
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Medicina Clinica, 1992
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Multiple Sclerosis Journal, 2015
Vitamin D deficit is considered an important risk factor for many inflammatory and autoimmune dis... more Vitamin D deficit is considered an important risk factor for many inflammatory and autoimmune diseases. To investigate the influence of the multiple sclerosis (MS)-associated regulatory variant rs10877013 on the expression of genes involved in vitamin D activation (CYP27B1), vitamin D receptor (VDR), and vitamin D degradation (CYP24A1) under inflammatory environment or vitamin D. We used lipopolysaccharide and interferon-gamma (LPS+IFNγ) activated monocytes from 119 individuals and vitamin D-stimulated lymphoblastoid cell lines (LCLs, n = 109) of 1000 genomes to quantify the mRNA expression of vitamin D genes by quantitative reverse transcription polymerase chain reaction (RT-qPCR). We found that CYP27B1 mRNA expression level was associated with the rs10877013 genotypes (p = 5.0E-6) in LPS+IFNγ treated monocytes, but not in vitamin D-stimulated LCLs. Inversely, rs10877013 genotypes were associated with VDR expression in LCLs (p = 6.0E-4) but not in monocytes. Finally, CYP24A1 was highly induced by the active form of vitamin D and its expression correlated with the expression of VDR in LCLs but neither the MS-associated variant in the region (rs2248359) nor any other variant located in 1 Mb around CYP24A1 was associated with its expression. The MS-associated variant rs10877013 is a genetic determinant that affects the functioning of the vitamin D system linking environmental and genetic factors.
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Neurochemistry international, 1997
The analysis of chromatin structure in cases of human spongiform encephalopathies could show the ... more The analysis of chromatin structure in cases of human spongiform encephalopathies could show the possible involvement of apoptosis in neuronal cell death. Genomic DNA was purified from peripheral blood lymphocytes and from a biopsy of the brain cortex in a case of Creutzfeldt-Jakob disease. Restriction fragment polymorphism with AspI, PvuII, Del and NspI showed the pattern of wild type PrP gene. The DNA purified from the brain consisted of partially degraded DNA in internucleosomal-sized fragments, whereas the DNA from peripheral blood lymphocytes showed the high molecular weight of unbroken DNA. These results are consistent with the possible activation in vivo of the apoptotic endonuclease and the internucleosomal fragmentation of DNA of the brain cortex in the patient affected by Creutzfeldt-Jakob disease, suggesting the involvement of apoptosis in neuronal cell death in human spongiform encephalopathy.
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Revista de neurologia
We present a case of multiple progressive occlusions of intracranial arteries, a variety of Taver... more We present a case of multiple progressive occlusions of intracranial arteries, a variety of Taveras' syndrome, without smoke spirals, which may be confused with other multifocal disorders. A 30 year old woman was admitted to hospital with a clinical picture of fluctuating paresia of her left limbs, blurred vision and urgency of micturition which partially recovered. On examination there was paresia of the left arm, generalized increased reflexes and facial asymmetry. On MRI there were areas of marked hyperintensity at T2. Some of these took up gadolinium at T1 and had a serpiginous pattern, compatible with vasculopathy. On angiography, stenosis and filling defect were seen in the left carotid artery. The anterior cerebral and left Sylvian arteries were filled by the vertebrobasilar system via the posterior communicating artery and an anomalous trigeminal artery. The clinical picture of multiple progressive occlusions of intracranial arteries is a variety of moya-moya disease, without the typical smoke spirals, which may lead to confusion with clinical pictures of arteritis and demyelinating disorders if angiography is not done, since this is essential for diagnosis.
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Revista de neurologia
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Revista Argentina de Radiología, 2015
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Journal of medical genetics, Jan 16, 2015
A recent large-scale study in multiple sclerosis (MS) using the ImmunoChip platform reported on 1... more A recent large-scale study in multiple sclerosis (MS) using the ImmunoChip platform reported on 11 loci that showed suggestive genetic association with MS. Additional data in sufficiently sized and independent data sets are needed to assess whether these loci represent genuine MS risk factors. The lead SNPs of all 11 loci were genotyped in 10 796 MS cases and 10 793 controls from Germany, Spain, France, the Netherlands, Austria and Russia, that were independent from the previously reported cohorts. Association analyses were performed using logistic regression based on an additive model. Summary effect size estimates were calculated using fixed-effect meta-analysis. Seven of the 11 tested SNPs showed significant association with MS susceptibility in the 21 589 individuals analysed here. Meta-analysis across our and previously published MS case-control data (total sample size n=101 683) revealed novel genome-wide significant association with MS susceptibility (p<5×10(-8)) for all s...
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Revista de neurologia
Lyme disease is a complex infectious disease affecting multiple organic systems. The most frequen... more Lyme disease is a complex infectious disease affecting multiple organic systems. The most frequent complications are of a dermatological, rheumatological, ophthalmological, cardiac and neurological nature. Among the neurological complications, pseudotumour cerebri is considered to be a rare manifestation of the disease. Hypothyroidism, however, is known to be only infrequently associated to pseudotumour cerebri. Paparone recently reported a case in which Lyme disease and primary hypothyroidism were concurrent, and Becker and Trock described the case of three patients with concurrent thyrotoxicosis and Lyme disease. We present the case of a 19 year old female with pseudotumour cerebri and hypothyroidism secondary to autoimmune thyroiditis, which improved after treating her for concomitant Lyme. We suggest there is a common aetiopathogenic connection between the three processes through autoimmune thyroiditis triggered by Borrelia burgdorferi. Thus, in this patient, the pseudotumour cerebri could be due to either a direct mechanism, triggered by B. burgdorferi, or indirectly, through hypothyroidism secondary to thyroiditis induced by B. burgdorferi, or perhaps to both mechanisms. It might be wise to consider infection by B. burgdorferi in patients with pseudotumour cerebri or thyroiditis coming from areas in which Lyme disease is endemic
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Brain : a journal of neurology, Jan 10, 2015
Prevention of irreversible disability is currently the most important goal of disease modifying t... more Prevention of irreversible disability is currently the most important goal of disease modifying therapy for multiple sclerosis. The disability outcomes used in most clinical trials rely on progression of Expanded Disability Status Scale score confirmed over 3 or 6 months. However, sensitivity and stability of this metric has not been extensively evaluated. Using the global MSBase cohort study, we evaluated 48 criteria of disability progression, testing three definitions of baseline disability, two definitions of progression magnitude, two definitions of long-term irreversibility and four definitions of event confirmation period. The study outcomes comprised the rates of detected progression events per 10 years and the proportions of the recorded events persistent at later time points. To evaluate the ratio of progression frequency and stability for each criterion, we calculated the proportion of events persistent over the five subsequent years once progression was achieved. Finally,...
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PloS one, 2015
Multiple sclerosis (MS) is a neurodegenerative, autoimmune disease of the central nervous system.... more Multiple sclerosis (MS) is a neurodegenerative, autoimmune disease of the central nervous system. Genome-wide association studies (GWAS) have identified over hundred polymorphisms with modest individual effects in MS susceptibility and they have confirmed the main individual effect of the Major Histocompatibility Complex. Additional risk loci with immunologically relevant genes were found significantly overrepresented. Nonetheless, it is accepted that most of the genetic architecture underlying susceptibility to the disease remains to be defined. Candidate association studies of the leukocyte immunoglobulin-like receptor LILRA3 gene in MS have been repeatedly reported with inconsistent results. In an attempt to shed some light on these controversial findings, a combined analysis was performed including the previously published datasets and three newly genotyped cohorts. Both wild-type and deleted LILRA3 alleles were discriminated in a single-tube PCR amplification and the resulting ...
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Multiple sclerosis (Houndmills, Basingstoke, England), Jan 21, 2015
We aimed to analyse the effect of the introduction of fingolimod, the first oral disease-modifyin... more We aimed to analyse the effect of the introduction of fingolimod, the first oral disease-modifying therapy, on treatment utilisation and persistence in an international cohort of patients with multiple sclerosis (MS). MSBASIS, a prospective, observational sub-study of the MSBase registry, collects demographic, clinical and paraclinical data on patients followed from MS onset (n=4718). We conducted a multivariable conditional risk set survival analysis to identify predictors of treatment discontinuation, and to assess if the introduction of fingolimod has altered treatment persistence. A total of 2640 patients commenced immunomodulatory therapy. Following the introduction of fingolimod, patients were more likely to discontinue all other treatments (hazard ratio 1.64, p<0.001) while more patients switched to fingolimod than any other therapy (42.3% of switches). Patients switched to fingolimod due to convenience. Patients treated with fingolimod were less likely to discontinue trea...
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PLOS ONE, 2015
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Brain and Behavior, 2015
To assess the effectiveness of glatiramer acetate (GA) compared to other multiple sclerosis (MS) ... more To assess the effectiveness of glatiramer acetate (GA) compared to other multiple sclerosis (MS) therapies in routine clinical practice. Observational cohort study carried out in MS patients treated with GA (GA cohort) or other MS therapies -switched from GA- (non-GA cohort). Study data were obtained through review of our MS patient database. The primary endpoint was the Expanded Disability Status Scale (EDSS) scores reached at the end of treatment/last check-up. A total of 180 patients were included: GA cohort n = 120, non-GA cohort n = 60. Patients in the GA cohort showed better EDSS scores at the end of treatment/last check-up (mean ± SD, 2.8 ± 1.8 vs. 3.9 ± 2.2; P = 0.001) and were 1.65 times more likely to show better EDSS scores compared to the non-GA cohort (odds ratio, 0.606; 95%CI, 0.436-0.843; P = 0.003). Patients in the GA cohort showed longer mean time to reach EDSS scores of 6 (209.1 [95%CI, 187.6-230.6] vs. 164.3 [95%CI, 137.0-191.6] months; P = 0.004) and slower disability progression (hazard ratio, 0.415 [95%CI, 0.286-0.603]; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). The annualized relapse rate was lower in the GA cohort (mean ± SD, 0.5 ± 0.5 vs. 0.8 ± 0.5; P = 0.001) and patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; quality of life was improved in this study cohort compared to the non-GA cohort (mean ± SD, 0.7 ± 0.1 vs. 0.6 ± 0.2; P = 0.01). GA may slow down the progression of EDSS scores to a greater extent than other MS therapies, as well as achieving a greater reduction in relapses and a greater improvement in patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; quality of life. Switching from GA to other MS therapies has not proved to entail a better response to treatment.
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Revista de neurologia
The assessment of the cognitive impairment in the multiple sclerosis disease is one of the most r... more The assessment of the cognitive impairment in the multiple sclerosis disease is one of the most relevant challenges nowadays. An essential objective is to obtain diverse approaches that allow valuing objectively this impairment and its correlation with physiological variables. To analyze the possible modulations in physiological components of the information processing (ERPs) related with an attentional deficit in diverse classes of patients with multiple sclerosis. 17 patients with remitting-relapsing multiple sclerosis, 9 patients with benign multiple sclerosis and 19 healthy subjects participated in the study. Behavioral performance in a visuo-spatial task (Posner paradigm) and later, an auditory oddball test was carried out where electroencephalography signal was registered to obtain ERPs. Correlation analyses were calculated between patient variables (EDSS or disease duration) and psychophysiological variables. A delay in the reaction time during the development of the Posner t...
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Annals of Clinical and Translational Neurology, 2015
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Revista de neurologia
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Revista de neurologia
Spinal cord infarction is the commonest vascular disorder of the spinal cord, but its incidence i... more Spinal cord infarction is the commonest vascular disorder of the spinal cord, but its incidence is low and difficulty in diagnosis means that often it is not recognized. Although cases of spinal cord infarction have been reported as complicating angiographic procedures, it rarely occurs nowadays. We describe a case of spinal cord infarction following coronariography. The patient was a 61 year-old man with ischemic cardiopathy who was admitted to our hospital for coronariographic study. Immediately after the study had been done, the patient complained of acute, intense lumbar pain with paraesthesia and progressive weakness of his legs, developing paraparesia and sphincter disorders. Magnetic resonance of the spine was done and in the spinal cord an oval lesion was seen in the medullar cone which was compatible with infarction. Six months later this finding was unchanged. A spinal infarction as a complication of invasive vascular studies, such as angiographies, is exceptional nowadays...
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The American journal of tropical medicine and hygiene, 1998
An undescribed rickettsia was directly analyzed with specific rickettsial molecular biology tools... more An undescribed rickettsia was directly analyzed with specific rickettsial molecular biology tools on Ixodes ricinus L. collected in different localities of the province of Cadiz (southwestern Spain). On the basis of the results of the citrate synthase (glta) gene, 190 kD-outer membrane protein (rOmpA) gene, and 16S ribosomal RNA (16S rRNA) gene partial sequence data, it was found that this rickettsia is sufficiently genetically distinct from other Rickettsia to be considered a distinct taxonomic entity. The isolation and culture of this organism, as well as comparative antigenic analysis, are required to ensure its conclusive taxonomic placement among spotted fever rickettsiae. The epidemiologic role of this new rickettsial agent and its possible pathogenicity to wild and domestic animals or humans is still unknown and needs to be investigated.
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Papers by Guillermo Izquierdo