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J C Alvarez-Cermeño

Publications and source records attributed to J C Alvarez-Cermeño.

At least 19 recordsLinked to original sources
PubMed2006

Clinically isolated syndromes: a new oligoclonal band test accurately predicts conversion to MS.

BACKGROUND: Patients with a clinically isolated demyelinating syndrome (CIS) are at risk of developing a second attack, thus converting into clinically definite multiple sclerosis (CDMS). Therefore, an accurate prognostic marker for that conversion might allow early treatment. Brain MRI and oligoclonal IgG band (OCGB) detection are the most frequent paraclinical tests used in MS diagnosis. A new OCGB test has shown high sensitivity and specificity in differential diagnosis of MS. OBJECTIVE: To evaluate the accuracy of the new OCGB method and of current MRI criteria (MRI-C) to predict conversion of CIS to CDMS. METHODS: Fifty-two patients with CIS were studied with OCGB detection and brain MRI, and followed up for 6 years. The sensitivity and specificity of both methods to predict conversion to CDMS were analyzed. RESULTS: OCGB detection showed a sensitivity of 91.4% and specificity of 94.1%. MRI-C had a sensitivity of 74.23% and specificity of 88.2%. The presence of either OCGB or MRI-C studied simultaneously showed a sensitivity of 97.1% and specificity of 88.2%. CONCLUSIONS: The presence of oligoclonal IgG bands is highly specific and sensitive for early prediction of conversion to multiple sclerosis. MRI criteria have a high specificity but less sensitivity. The simultaneous use of both tests shows high sensitivity and specificity in predicting clinically isolated demyelinating syndrome conversion to clinically definite multiple sclerosis.

Adolescent↗
PubMed2004

An ultrasensitive method for the detection of oligoclonal IgG bands.

We have developed an ultrasensitive isoelectrofocusing (IEF) method for the detection of oligoclonal (OGC) IgG bands in cerebrospinal fluid (CSF) and sera. In this procedure, double antibody and peroxidase immunodetection have been substituted by a single antibody labelled with alkaline phosphatase. Alkaline phosphatase immunodetection not only improves tenfold the sensitivity of the assay but also gives a sharper pattern resolution making the interpretation easier and increases the specificity of this technique. This preliminary report should be validated in a larger number of patients with and without multiple sclerosis (MS).

Alkaline Phosphatase↗
PubMed2003

Caspase inhibitors protect against neuronal apoptosis induced by cerebrospinal fluid from multiple sclerosis patients.

Neuronal apoptosis has recently been implicated in multiple sclerosis (MS). Apoptotic cell death of neurons is induced in cultures exposed to cerebrospinal fluid (CSF) from MS patients. Since caspases are essential in the regulation of apoptosis, direct evidence was sought linking caspases to CSF-induced neuronal death. Caspase activity was measured in cell extracts from MS CSF-treated cultured neurons by the cleavage of caspase-1 and caspase-3 substrates. Caspase-3 activity, but not caspase-1, was induced in neuronal cultures in response to MS CSF treatment. This caspase-3 activity was inhibited in vitro by Ac-YVAD-cmk and Ac-DEVD-cmk caspase inhibitors. Treatment of MS CSF-incubated neuronal cells with these caspase inhibitors completely preserved neuronal survival and largely attenuated DNA fragmentation detected in situ. These findings show that neuronal cells are rescued from MS CSF-induced death by caspase inhibitors and suggest ways to treat MS.

Adolescent↗
PubMed2002

Intrathecal IgM synthesis predicts the onset of new relapses and a worse disease course in MS.

BACKGROUND: The authors have recently described that intrathecal IgM synthesis (ITMS) correlates with a higher disability in patients with clinically definite MS (CDMS). OBJECTIVE: To follow-up a group of patients with MS in the initial stages of the disease to evaluate if the presence of ITMS correlates with a worse evolution. METHODS: Oligoclonal IgM bands were performed in 22 patients with MS with a mean of 1.14 months of evolution. Patients were followed for a period ranging from 6 to 36 months (mean, 21.4 months). During follow-up, time to conversion to CDMS, number of relapses, and changes in Expanded Disability Status Scale (EDSS) score were evaluated. RESULTS: Patients were divided into two groups according to the presence (Group 1, 10 patients) or absence (Group 2, 12 patients) of ITMS. No clinical differences were observed between the groups at inclusion in the study. During the follow-up, the probability of conversion to CDMS was greater in Group 1 (90% of the patients had converted to CDMS after 8 months of follow-up) than in Group 2 (51% of patients had converted to CDMS after 36 months of follow-up) (p = 0.0001). Patients from Group 1 had more relapses (mean, 2.0) than those from Group 2 (mean, 0.58) (p = 0.02). At the end of the study, patients from Group 1 had higher EDSS scores (mean, 1.70) than those from Group 2 (mean, 0.79) (p = 0.02). CONCLUSION: The presence of oligoclonal IgM bands in CSF can be a prognostic marker in the early phases of MS.

Adolescent↗
PubMed2002

Intrathecal IgM synthesis in neurologic diseases: relationship with disability in MS.

The authors studied the intrathecal IgM synthesis (ITMS) in paired sera and CSF samples from 65 patients with MS, 28 with CNS infection, 40 with other neurologic diseases and eight control subjects. ITMS was found in 30 patients with MS and in 20 with CNS infection, but not in patients with other neurologic diseases or in control subjects. In infectious samples, the ITMS is likely a primary response. In MS group, it was associated with higher Expanded Disability Status Scale index (p = 0.017).

Adult↗
PubMed2002

Increased levels of IL-15 mRNA in relapsing--remitting multiple sclerosis attacks.

IL-15 is a proinflammatory cytokine which has recently been implicated in multiple sclerosis (MS) pathogenesis, where it may play a role in the initiation and/or progression of the disease. We have used reverse transcriptase-polymerase chain reaction (RT-PCR) to study IL-15 mRNA levels in peripheral blood mononuclear cells (PBMC) from healthy controls and relapsing-remitting MS (RRMS) patients in a stable phase of the disease and during a bout, both before and after corticosteroid treatment (CST). IL-15 mRNA expression was found to be similar in controls and stable patients. We have detected an increased level of IL-15 mRNA in PBMC of patients with a relapse, which was maintained after CST. We have also found an inverse correlation between PBMC IL-15 mRNA levels at the onset of the relapse and the time elapsed since the previous attack, as well as an absence of correlation between IL-15 mRNA levels and the patient demographic and clinical characteristics. Results in the present work further suggest a role for IL-15 in MS pathophysiology.

Adrenal Cortex Hormones↗
PubMed2001

A sensitive and reproducible method for the detection of oligoclonal IgM bands.

We have developed a sensitive and specific isoelectrofocusing (IEF) method for the detection of oligoclonal (OGC) IgM in the cerebrospinal fluid (CSF) and sera. In this procedure, ampholytes, in the range pH 5-8, were used to improve the resolution, and serum was diluted in saline to avoid IgM precipitation. Samples were treated with 50 mM dithiothreitol (DTT) at pH 9.5 to reduce IgM and improve the migration of the protein. Using an anti-IgM labelled with alkaline phosphatase, the limit of detection was found to be 0.1 ng in 5 microl of sample.

Buffers↗
PubMed2000

Axonal damage induced by cerebrospinal fluid from patients with relapsing-remitting multiple sclerosis.

The importance of axonal damage in multiple sclerosis (MS) has been recently stressed in proton magnetic resonance spectroscopy and pathological studies, but the exact mechanism producing this damage is unknown. The aim of our study was to ascertain whether soluble mediators present in the cerebrospinal fluid (CSF) of patients with relapsing-remitting MS could induce neuron injury in culture. Different biochemical and cytochemical parameters were determined in primary embryonal rat neuron cultures following 8 days of exposure to CSF. Cytotoxic activity was evaluated with a blue formazan production colorimetric assay. Morphological and immunocytochemical studies performed with antibodies against beta-tubulin revealed neuritic fragmentation, axonal damage and cellular shrinkage indicating apoptosis. Detection of apoptosis was carried out using the fluorescent DNA-binding dye Hoechst 33342, as well as by a Terminal deoxynucleotidyl transferase-mediated dUTP Nick End-Labeling assay. We observed that soluble factors in CSF from patients with "aggressive" MS i.e, those with poor recovery after relapses, induced neurite breakdown and neuronal apoptosis in cultures. Neuron injury is not related with blood-brain barrier dysfunction nor with IgG index. Interestingly, CSF from patients with "non-aggressive" MS i.e., relapsing-remitting patients with a good recovery after relapses, did not induce any damage. In conclusion, we report that CSF from patients with aggressive MS bears soluble mediators that induce axonal damage and apoptosis of neurons in culture. These mediators can be present during the first attack of the disease, and the neuronal damage caused could be related to the functional deficit of these MS patients.

Adolescent↗
PubMed2000

Interferon beta-1b treatment in patients with relapsing--remitting multiple sclerosis under a standardized protocol in Spain.

OBJECTIVE: A protocol system is being used in Spain for the prescription of innovative drugs including interferon beta-1b (IFNbeta-1b). Petitions for dispensing and reimbursement are based on the inclusion and exclusion criteria of pivotal trials, and are reviewed individually for approval by specialist committees. To estimate the performance of IFNbeta-1b in the clinical setting, data collected by the INSALUD and regional health services of Andalusia and Catalonia, together responsible for the healthcare of nearly 30 million individuals, were compiled in a common database for analysis. METHODS: Data comprise demographic and disease characteristics at the time of petition and at follow-up 3 months after treatment initiation and every 6 months thereafter. Efficacy was estimated by mean number of relapses per year, proportion of relapse-free patients, and disease progression as measured by the Expanded Disability Status Scale (EDSS). Safety parameters included adverse events and laboratory analyses. RESULTS: Between September 1995 and database cutoff in mid-1998, petitions of 1419 patients were approved for IFNbeta-1b treatment. Patients were homogenous across the three databases and in the subgroups of patients completing 1 year (n = 940) and 2 years (n = 302) of treatment. There was a marked decrease in the mean number of relapses in the first 12 months of IFNbeta-1b treatment for the 938 patients documented for 12 months, with a mean of 0.4 (+/- 0.7 SD) relapses per patient and year, and a 2-year mean of 0.9 (+/- 1.20 SD) in the 302 patients documented for 24 months. Of the 938 patients followed for > or = 12 months, 505 (53.8%) were documented as being relapse-free during 12 months of treatment, and 146 (48.3%) of the 302 patients followed for > or = 24 months, were relapse-free during 24 months of treatment. There were no differences in mean or median EDSS scores between baseline and months 12 and 24. Skin disorders were the most frequent adverse events, reported in over one-third of all patients; there were 159 injection site events, most frequently erythema (115 events). Systemic AEs pointing towards flu-like symptoms were reported in 288 of 1419 patients (20.3%). Leukopenia was the most frequently reported laboratory event. Elevations in liver transaminases were noted for 12 patients (0.8%) with SGOT increase and 7 (0.5%) with SGPT increase. CONCLUSION: The protocol system has helped make IFN treatment available to 8-10% of the estimated 15,000-18,000 MS patients in the regions studied. In terms of efficacy, IFNbeta-1b performed in line with the pivotal study results. The safety profile of IFNbeta-1b was consistent with the published findings and the drug labelling, and no new side effects or increased incidence of known side effects was observed.

Adjuvants, Immunologic↗
PubMed1999

Regulatory effects of cytokines and cyclosporine A on peripheral blood mononuclear cells from stable multiple sclerosis patients.

The proliferative response (PR) of peripheral blood mononuclear cells (PBMC) to lectins such as phytohemaglutinin (PHA), anti-CD3 monoclonal antibodies such as OKT-3 or phorbol esters such as tetradecanoyl-phorbol 13-acetate (TPA) was investigated in 18 stable multiple sclerosis (MS) patients (9 untreated and 9 treated patients) and 10 healthy controls. PBMC from untreated MS patients showed a significantly higher PR to PHA than healthy controls. The PR of PHA, anti-CD3 or TPA stimulated PBMC from treated patients was lower than that from untreated MS patients. Mitogen stimulated PBMC from untreated patients shown both increased sensitivity to the stimulatory effect of IL-2 and increased resistance to the inhibitory effect of IL-10 and IFN-alpha. The addition of IL-2 increased the PR in PHA-stimulated PBMC from untreated MS patients, but not in those from treated MS patients and healthy controls. Mitogen stimulated cells from untreated patients were more resistant to the inhibitory effect of IL-10 and IFN-alpha than PBMC from either treated MS patients or healthy controls. Cyclosporine A (CsA) inhibited the PR and the expression of activation antigens induced by PHA in PBMC from the three groups of subjects. This inhibitory effect of CsA have was enhanced by the addition of IFN-alpha.

Adult↗
PubMed1998

Induction of apoptosis by cerebrospinal fluid from patients with primary-progressive multiple sclerosis in cultured neurons.

We have studied the noxious effect of cerebrospinal fluids (CSF) from patients with primary-progressive multiple sclerosis (MS) on cultured neurons. Cells were exposed to CSF for 8 days and the possible neuronal damage was determined. Morphological studies with phase-contrast microscopy showed cellular shrinkage indicating apoptosis. CSF-induced apoptosis as evidenced by the fluorescent DNA-binding dye Hoechst 33342, as well as by the TUNEL-reaction, was only present in primary-progressive MS patients with a worsening disease. This neuron injury did not correlate with blood-brain barrier dysfunction nor with intrathecal IgG synthesis. On the contrary, CSF from either stable primary-progressive or other non-inflammatory neurological diseases, did not induce any culture damage. Undetectable or low similar tumor necrosis factor-alpha (TNF-alpha) levels (range to 8.7 pg/ml) were found in the CSFs tested regardless they damage cultures or not. These results suggest that soluble factors, other than TNF-alpha, molecules transudated from blood or IgG, present in the CSF of active primary-progressive patients with MS induce neuronal apoptosis.

Animals↗
PubMed1998

The expression of integrins on activated T-cells in multiple sclerosis. Effect of intravenous methylprednisolone treatment.

We studied the effect of intravenous methylprednisolone (MP) on the expression of the integrins, LFA-1 and VLA-4, on activated blood T-lymphocytes in 17 patients with relapses of clinically definite relapsing-remitting MS. MP treatment did not induce changes in the expression of CD3, CD4, DR, LFA-1 or VLA-4 markers when measured in the total population of lymphocytes in MS patients in relation to treatment. Treatment influenced neither the LFA-1 nor VLA-4 positive cells within the CD3+ population. MP treatment clearly decreased the DR+ CD3+ cells (P < 0.01) and the percentage of DR+ CD3+ lymphocytes bearing VLA-4 (P < 0.01). However, this was not the case when we studied the percentage of lymphocytes which expressed LFA-1. Glucocorticoids did not influence the mean intensity of the expression of the two integrins quantified in either total or DR+ CD3+ lymphocytes. Although, further research seems warranted to investigate a possible effect of MP on lymphocyte integrin function, this work corroborates the idea that MP treatment may interfere with the mechanisms of T-cell migration into CNS, thus modulating the activity of multiple sclerosis.

Adjuvants, Immunologic↗
PubMed1998

Slow allotypic variants of the NAT2 gene and susceptibility to early-onset Parkinson's disease.

OBJECTIVE: To determine the frequency and the linkage distribution of seven mutations at the polymorphic gene coding for the arylamine N-acetyl transferase (NAT2; EC 2.3.1.5) in 121 unrelated patients with sporadic PD and in 121 unrelated healthy volunteers. METHODS: The study was performed with mutation-specific PCR using genomic DNA obtained from blood of the probands. RESULTS: Comparison of the NAT2 genotypes of the overall PD patients and control subjects did not indicate statistically significant differences. However, patients with early-onset PD (onset before the age of 50 years, n=37) showed a higher frequency of slow-acetylation genotypes (78.4% patients) compared with both healthy control subjects (55.4%) and with late-onset (onset after 51 years of age, n=84) PD patients (54.8%). Such a difference was statistically significant (p < 0.015) and was the result of a homogeneous increase in the frequency of slow-acetylation alleles. All subgroups analyzed in the study were in Hardy-Weinberg equilibrium for mutations at the NAT2 gene. CONCLUSIONS: Slow-acetylation-mutated alleles may be considered low-penetrance genes in early-onset PD pathogenesis, with a relative risk ratio for individuals with slow-acetylation genotype of 2.92 (95% CI, 1.26 to 6.78). This study provides evidence for the interaction of genetic and environmental factors in the etiology of sporadic PD.

Adult↗
PubMed1998

[Paroxysmal dyskinesias as the initial manifestation of multiple sclerosis].

We herein report two patients with paroxysmal dyskinesias (PD) as the initial manifestation of multiple sclerosis (MS). PD can occur in clinically definite MS or rarely be the presenting symptom. They are produced by demyelinating lesions at any level in the motor pathway or in the thalamus. MRI disclosed an area of demyelination in the posterior limb of the internal capsule contralateral to the PD in the patients reported herein. PD associated with MS do not adjust completely to the accepted classifications of PD, therefore they should be considered a special category of dyskinesias.

Adult↗