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Oscar Fernández

Publications and source records attributed to Oscar Fernández.

10 recordsLinked to original sources
PubMed2006

Interferon receptor expression in multiple sclerosis patients.

To determine the gene expression of IFNAR1, IFNAR2 and MxA protein and the association with IFNbeta treatment response in MS patients. MS patients treated with IFNbeta had a significant decrease in IFNAR1 and IFNAR2 expression, and a significant increase in MxA compared to non-treated patients and healthy controls. Also, those patients who had a good response to treatment had a significant decrease in IFNAR1 and IFNAR2 expression compared to non-responders, non-treated patients and healthy controls. IFNbeta influences the expression of its receptors, and is greater in patients who respond to IFNbeta treatment. This down-regulation could be indicative of the response to IFNbeta.

Adult↗
PubMed2005

IFNAR1 and IFNAR2 polymorphisms confer susceptibility to multiple sclerosis but not to interferon-beta treatment response.

We investigated the role of three polymorphisms in the IFNAR1 (SNPs 18417 and -408) and IFNAR2 (SNP 11876) genes in multiple sclerosis (MS) susceptibility and in the IFNbeta treatment response in a group of 147 patients and 210 controls undergoing interferon therapy during the last 2 years. Only the 18417 and the 11876 SNPs showed an association with disease susceptibility (p=0.001 and 0.035, respectively) although no differential genotype distribution were observed between interferon responders and non-responder MS patients. No alteration of the expression level of IFNAR-1 was observed with respect to the -408 genotypes or to interferon treatment response. These data suggest a role for the IFNAR pathway in susceptibility to MS.

Adolescent↗
PubMed2004

Effects of the multiple sclerosis associated -330 promoter polymorphism in IL2 allelic expression.

The -330 IL2 gene promoter polymorphism has been associated with multiple sclerosis (MS) [J. Neuroimmunol. 119 (2001) 101], but the basis underlying this association remains unknown to date. In the present work, we have found that IL2 promoter-luciferase constructs, transfected in Jurkat cell line, showed twofold higher levels of gene expression in the -330 G allele. However, the transcriptional effect of this polymorphism in lymphocytes showed that the G allele was related to lower expression of IL2. This difference increased in the patient group. Divergence between in vivo and in vitro influence of the -330 IL2 promoter polymorphic site suggests the existence of additional unknown polymorphisms affecting gene regulation. Our data show an increased IL2 expression among GT and TT genotypes previously associated with susceptibility to MS.

Alleles↗
PubMed2004

Interferons in relapsing-remitting multiple sclerosis: are there benefits from long-term use?

Multiple sclerosis (MS) is one of the most common chronic neurological diseases in young adults in western countries. An important aspect of treatment of this disease is the use of interferons (IFNs). These are molecules with antiviral, immunomodulatory, antiproliferative and hormonal activities. IFNbeta, a class I IFN, has been used extensively in the therapy of MS, particularly in its relapsing-remitting (RRMS) phase, the most frequent clinical form of the disease. Although the available evidence from published clinical trials is difficult to evaluate because of methodological differences, an unbiased review of the data reveals sufficient evidence to conclude that treatment with IFNbeta in RRMS is both efficacious and safe, at least over the periods so far investigated (up to 4-6 years). While there is no reason to suspect that IFNbeta should not continue to be efficacious and safe over the longer term, studies investigating these questions over longer periods and including greater numbers of patients are needed.

Clinical Trials as Topic↗
PubMed2003

Validation of diagnostic magnetic resonance imaging criteria for multiple sclerosis and response to interferon beta1a.

In the recently proposed diagnostic criteria for multiple sclerosis (MS) by McDonald, the modified magnetic resonance imaging (MRI) Barkhof criteria have been incorporated. We examined the validity of this implementation in the Early Treatment of MS study, a randomized, double-blind, placebo-controlled study of 22 microg interferon beta1a given subcutaneously once weekly in 309 patients with a first episode consistent with demyelinating disease (and abnormal MRI). Conversion to clinically definite MS (CDMS) within 2 years of follow-up, as evidenced by a new clinical episode, occurred in 41% of patients (independent of treatment) with gadolinium enhancement or nine or more T2 lesions versus 11% of those without either finding (p = 0.017); similarly, proportions converting were 44% versus 31% for infratentorial lesions (p = 0.026), 40% versus 35% for juxtacortical lesions (p = 0.413), and 41% versus 17% for three or more periventricular lesions (p = 0.034). The rate of conversion to CDMS based on the number of modified Barkhof criteria was 22% for two or fewer positive criteria, increasing to 47% with four positive criteria. For a cutoff of three positive criteria, the hazard ratio for time to CDMS was 2.3 (95% confidence interval, 1.17-4.55; p = 0.016). Treatment effect seemed more evident as the number of positive criteria increased, and the number of patients needed to avoid one patient converting to CDMS decreased from 50 in patients with one or two positive criteria to 5.6 in patients with four positive criteria. However, the study was not powered to detect statistically significant treatment by variable interaction, and this remains an important issue for further study.

Adjuvants, Immunologic↗
PubMed2002

Mechanisms and current treatments of urogenital dysfunction in multiple sclerosis.

The majority of patients with multiple sclerosis (MS) suffer from lower urinary tract symptoms and sexual dysfunction at some stage of the disease. This has a negative impact on the quality of life of patients as well as causing concern to caregivers and family. Neurologists can now treat most of these symptoms by a number of pharmacological and nonpharmacological methods. This review presents the neuroanatomy, neurophysiology, neuropharmacology and pathophysiology of the urinary bladder and sexual organs, and the biological mechanisms underlying urogenital dysfunction in MS patients. Current treatment options for urinary and sexual dysfunction are reviewed. As most urogenital symptoms of MS can now be treated by conservative means, expert urological or gynaecological consultation should be requested only if more aggressive diagnostic or therapeutic measures are needed.

Autonomic Nervous System↗
PubMed2002

Combination therapy with interferon beta-1b and azathioprine in secondary progressive multiple sclerosis. A two-year pilot study.

Combination therapy may benefit the subgroup of patients with secondary progressive multiple sclerosis (SPMS) who do not respond to interferon beta (IFNB). We performed a two-year study of azathioprine (AZA) combined with IFNB-1b in SPMS patients who had not responded well to IFNB-1b alone. Patients with SPMS were eligible for this non-controlled prospective study if they had two or more relapses requiring corticosteroid treatment or deteriorated by at least 0.5 points on the Expanded Disability Status Scale (EDSS) while on IFNB-1b in the year preceeding the study. Patients were to continue treatment with IFNB-1b (8 MIU qod, subcutaneous) and received AZA (50 mg tid, oral). Safety was assessed in terms of adverse reactions and laboratory measures graded according to the WHO toxicity scale. Efficacy was explored by changes in relapse rate, EDSS, 9-hole peg test (9-HPT), neuropsychological scores, and magnetic resonance imaging (MRI) results. Neutralizing antibodies (NAB) were measured. Ten SPMS patients (6 females) with a median EDSS score of 4.5 were enrolled. One patient withdrew because of gastrointestinal complaints, one was withdrawn owing to poor compliance, and 8 patients completed therapy. The only frequent side effect was lymphopenia, reported at least once in all patients. Annual relapse rate was reduced by approximately 50 % in the second year. There was a significant trend for EDSS increase. Total lesion load measured by MRI decreased at 12 and 24 months; only one patient had active lesions. No changes were seen in the 9-HPT. There was a significant improvement in neuropsychological tests after 24 months ( p = 0.045). One patient tested positive for NAB throughout the study, and transient NAB were detected in 4 patients. In conclusion, combination therapy with IFNB-1b and AZA was safe and generally well tolerated in patients with SPMS. Strict clinical and laboratory monitoring is recommended during this combination therapy.

Adjuvants, Immunologic↗
PubMed2002

Radiation therapy after high-dose chemotherapy with peripheral blood stem cell support for high-risk breast cancer.

Multidisciplinary treatment in high-risk breast cancer improves survival and local control. The feasibility and patterns of failure after several induction and high-dose consolidation regimens of chemotherapy were evaluated in this study. Between November 1990 and January 1997, 65 patients with histologically proven breast cancer American Joint Committee on Cancer stages II-III with four or more axillary lymph nodes positive or locally advanced breast cancer underwent high-dose chemotherapy (HDC) with peripheral stem cell support after surgery and induction chemotherapy. All patients were subsequently treated with radiotherapy (up to total doses of 50-60 Gy), which included the ipsilateral axilla and supraclavicular fossa and the chest wall or breast. A minimum follow-up period of 2 years from the completion of radiotherapy was required for analysis. Local control (LC), disease-free survival (DFS), overall survival (OS), and toxicity were evaluated. With a median follow-up of 62 months (range: 32-107 months), LC was 89%, and 5-year OS and DFS were 78% and 63%, respectively. Symptomatic pneumonitis developed in six patients (9%); only one patient had her radiotherapy interrupted because of hematologic toxicity. No treatment-related mortality was observed. Radiation therapy after HDC provides excellent local control rates without excessive toxicity. Delaying the start of irradiation until recovery from HDC does not seem to increase local failure rates.

Adult↗
PubMedDate not supplied

Relationship between the efficacy of rivastigmine and apolipoprotein E (epsilon4) in patients with mild to moderately severe Alzheimer disease.

Alzheimer disease is the most common form of dementia in Western countries and the leading cause of disability in the over-65 population. Apolipoprotein E (APOE) is a multifunctional protein implied in lipid metabolism and neurobiology. Polymorphisms of the APOE gene have been associated with a variety of medical disorders, from arteriosclerosis to AD. A high frequency of the APOE epsilon4 allele has been found in patients with AD and they seem to have a higher risk of developing the disease. Various authors have suggested a possible relationship between the efficacy of cholinesterase inhibitors and the presence of the APOE epsilon4 allele. The purpose of the present study was to compare prospectively the efficacy of rivastigmine in patients with mild to moderately severe AD presenting different polymorphisms of the APOE gene on chromosome 19 and to determine if there was a difference in the response to rivastigmine treatment in AD patients with the APOE epsilon4 allele (heterozygous or homozygous) versus patients who had other forms of APOE, such as epsilon2 and epsilon3. This was an open-label, nonrandomized, multicenter study in patients over 50 years of age diagnosed with mild to moderately severe AD. The results of the analysis of this study indicate that the presence of at least one APOE epsilon4 allele does not determine a difference in the response to treatment with rivastigmine. The data indicate that knowledge of the patient's genotype is not necessary for treatment with rivastigmine. It would be interesting in the future to analyze the interaction between these 2 factors using other available anticholinesterase drugs.

Aged↗