NFkappaB and AP-1 DNA binding activity in patients with multiple sclerosis.

Current evidence suggests that multiple sclerosis (MS) results from an autoimmune response mediated by T lymphocytes, which would be activated in the peripheral blood and migrate into the central nervous system. NFkappaB and AP-1 are two main transcription factors involved in T-cell activation. To investigate possible alterations in the activity of these factors in MS individuals, we have assayed NFkappaB and AP-1 DNA binding activity in peripheral blood mononuclear cells (PBMC). Binding activity was analyzed by gel mobility shift assay in MS patients compared with controls. No significant differences were found between the two groups, indicating no evidence of abnormalities associated with MS in NFkappaB or AP-1 binding activities in PBMC, both basally and after PMA+anti-CD3 antibody induction.

Aminoguanidine reduces apoptosis of circulating V Beta 8.2 T lymphocytes in Lewis rats with actively induced experimental autoimmune encephalomyelitis. Association with persistent inflammation of the central nervous system and lack of recovery.

Aminoguanidine therapy delayed the onset of actively induced EAE in Lewis rats, but recovery was impaired in most animals. In the central nervous system this was correlated with persistent inflammation and production of proinflammatory cytokines. In the periphery of aminoguanidine-treated animals, T lymphocytes showed increased proliferation against myelin basic protein, and the percentage of Vbeta 8.2(+) T lymphocytes undergoing early apoptosis was markedly decreased, although it was unchanged in Vbeta 8.2(+) T cells isolated from the spinal cord. These results suggest that the prolonged survival of circulating encephalitogenic cells achieved by aminoguanidine would favor a longer lasting entry of these cells into the nervous system resulting in persistent inflammation and lack of recovery.

[Spontaneous intracranial hypotension. Radiological findings]. / Hipotensión intracraneal espontánea. Hallazgos radiológicos.

INTRODUCTION: Spontaneous intracranial hypotension (SIH) is an uncommon condition. The main symptom is headache which appears on standing and is relieved by lying down. Diagnosis is confirmed if a CSF pressure of less than 6 cm of water is found in the absence of other causes of intracranial hypotension. OBJECTIVE: To describe the cranial MR and CT findings of 7 cases with SIH. MATERIAL AND METHODS: We studied 7 patients in whom the diagnosis had been confirmed by lumbar puncture. The findings of 5 cranial CT studies (not using contrast), 5 MR without gadolinium and 4 MR with gadolinium were studied. The CT were carried out during the first week after clinical signs appeared, and the MR at between 1 week and 4 months after onset. We reviewed previous findings in the literature. RESULTS: 1. Cranial CT: in one case there was an enlarged subarachnoid space; 2. MR without gadolinium: there was descent of the cerebellar tonsils in 4 patients, meningeal thickening in 5 cases and subdural collections in two patients. In no case was descent of the iter seen; 3. MR with gadolinium: aural contrast was taken up in all cases. CONCLUSIONS: The CT without contrast done at the onset of the condition did not usually give data which was useful for diagnosis. The principal MR findings in our series (meningeal thickening, descent of the cerebellar tonsils, subdural collections and gadolinium uptake) in an appropriate clinical context may be sufficient for diagnosis of this condition before lumbar puncture.

Cost-effectiveness of injectable disease-modifying therapies for the treatment of relapsing forms of multiple sclerosis in Spain.

OBJECTIVE: To compare the cost-effectiveness of injectable disease-modifying therapies (DMTs) for the first-line treatment of relapsing-remitting multiple sclerosis (RRMS) in Spain. METHODS: A Markov model was developed to estimate the cost-effectiveness of intramuscular interferon beta-1a (IM IFNß-1a), subcutaneous interferon beta-1a (SC IFNß-1a), interferon beta-1b (IFNß-1b) and glatiramer acetate (GA) relative to best supportive care in a hypothetical cohort of 1,000 RRMS patients in Spain. The model was developed from a societal perspective with a time horizon of 30 years. Natural history and clinical trial data were used to model relapse rates and disease progression. Cost and utility data were obtained from a published survey of multiple sclerosis patients in Spain. The primary outcome measure was cost per quality-adjusted life year (QALY) gained. Univariate and probabilistic sensitivity analyses were performed. RESULTS: Compared to best supportive care, the base case cost-effectiveness was 168,629 per QALY gained for IM IFNß-1a, 231,853 per QALY gained for IFNß-1b, 295,638 per QALY gained for SC IFNß-1a, and 318,818 per QALY gained for GA. Results were most sensitive to changes in DMT cost, utility values and treatment effect. CONCLUSIONS: In our cost-effectiveness analysis of first-line injectable DMTs in Spain, we found IM IFNß-1a to be more cost-effective than SC IFNß-1a, IFNß-1b or GA. Sensitivity analyses confirmed the robustness of these results.

Confirming the MS diagnosis.

Progress in understanding the pathophysiology of MS has shown that irreversible damage to the central nervous system may occur early in the disease course. Evidence from clinical trials suggests that part of this damage might be prevented by the early use of disease modifying drugs; this therefore increases the importance of an early MS diagnosis. All diagnostic criteria for MS have incorporated definitions for dissemination in space and in time, along with the exclusion of alternative diagnoses. The McDonald criteria include magnetic resonance imaging definitions for such concepts, which enable MS to be diagnosed much sooner, in many cases. This paper reviews the steps to be taken in the diagnostic evaluation of patients with suspected MS.

Tumor phyllodes de la mama: nuestra experiencia / Breast phyllodes tumor: our experience

Efectuamos un análisis retrospectivo de 8 pacientes con tumor phyllodes de la mama tratadas entre junio de 1971 y junio de 1993. La edad media fue de 44 años (19-74). Según su histología, 5 fueron benignos, 2 bordeline y 1 maligno. El seguimiento medio fue de 10,2 años (r: 1,7 a 22,1) en los benignos; 10,3 años y 6 meses respectivamente en los bordeline y 7 años en el maligno. En todos los casos el tratamiento fue quirúrgico: tumorectomía en los benignos, adenomastectomía subcutánea y mastectomía radical sin vaciamiento axilar en el maligno. La paciente con tumor bordeline presentó recurrencia local como phyllodes maligno a los 5 meses y metastasis pulmonares dos meses después, falleciendo a los 8 meses del diagnóstico. La recurrencia local presentaba un marcado sobrecrecimiento estromal, atipia moderada y elevado número de mitosis. Con excepción de una paciente que falleció por un IAM, las restantes seis continúan libres de enfermedad