Use of herbal remedies by multiple sclerosis patients: a nation-wide survey in Italy.

Though recent progress in multiple sclerosis (MS) treatment is remarkable, numerous unmet needs remain to be addressed often inducing patients to look for complementary and alternative medicines (CAM), especially herbal remedies (HR). HR use, scarcely investigated in MS, may cause adverse reactions (AR) and interfere with conventional treatment. We performed a survey aimed at evaluating use and attitudes towards HR and factor associated to HR use. Other CAM use and attitudes have been investigated as well. Multiple-choice questionnaires were distributed to MS out patients attending 14 Italian referral Centers. Multivariable logistic regression was used to identify HR use determinants. Present/past HR use for either MS or other diseases was reported in 35.6 % of 2419 cases (95 % CI 36.0-40.0 %). CAM use was reported in 42.5 % of cases. Independent predictors of HR use were represented by higher education, geographic area, dissatisfaction with conventional treatment of diseases other than MS and benefit perception from CAM use. Both HR and CAM use were not always disclosed to the healthcare professional. In conclusion, HR and other CAM appear to be popular among MS patients. The involvement of the healthcare professionals appears to be scarce with potential risk of AR or interference with conventional treatments.

Patients' needs in proton therapy: A survey among ten European facilities.

Aims: The number of Proton Therapy (PT) facilities is still limited worldwide, and the access to treatment could be characterized by patients' logistic and economic challenges. Aim of the present survey is to assess the support provided to patients undergoing PT across Europe. Methods: Through a personnel contact, an online questionnaire (62 multiple-choice and open-ended questions) via Microsoft Forms was administered to 10 European PT centers. The questionnaire consisted of 62 questions divided into 6 sections: i) personal data; ii) general information on clinical activity; iii) fractionation, concurrent systemic treatments and technical aspects of PT facility; iv) indication to PT and reimbursement policies; v) economic and/ or logistic support to patients vi) participants agreement on statements related to the possible limitation of access to PT. A qualitative analysis was performed and reported. Results: From March to May 2022 all ten involved centers filled the survey. Nine centers treat from 100 to 500 patients per year. Paediatric patients accounted for 10-30%, 30-50% and 50-70% of the entire cohort for 7, 2 and 1 center, respectively. The most frequent tumours treated in adult population were brain tumours, sarcomas and head and neck carcinomas; in all centers, the mean duration of PT is longer than 3 weeks. In 80% of cases, the treatment reimbursement for PT is supplied by the respective country's Health National System (HNS). HNS also provides economic support to patients in 70% of centers, while logistic and meal support is provided in 20% and 40% of centers, respectively. PT facilities offer economic and/or logistic support in 90% of the cases. Logistic support for parents of pediatric patients is provided by HNS only in one-third of centers. Overall, 70% of respondents agree that geographic challenges could limit a patient's access to proton facilities and 60% believe that additional support should be given to patients referred for PT care. Conclusions: Relevant differences exist among European countries in supporting patients referred to PT in their logistic and economic challenges. Further efforts should be made by HNSs and PT facilities to reduce the risk of inequities in access to cancer care with protons.

Risk of multiple sclerosis relapses when switching from fingolimod to cell-depleting agents: the role of washout duration.

BACKGROUND: Fingolimod (FTY) induces sequestration of lymphocytes in secondary lymphoid organs and the average lymphocyte recovery following discontinuation takes 1-2 months. It has been hypothesized that the therapeutic effects of subsequent cell-depleting agents may be compromised if initiated before lymphocyte recovery has occurred. OBJECTIVE: To assess the risk of relapses following FTY discontinuation and the initiation of a B/T cell-depleting agent in relation to washout duration using data from the Italian MS Register. METHODS: The risk of relapses was assessed in relation to different washout durations (< 6, 6-11, 12-17 and > / = 18 weeks) in patients starting alemtuzumab, rituximab, ocrelizumab or cladribine following FTY discontinuation. RESULTS: We included 329 patients in the analysis (226F, 103 M; mean age 41 ± 10 years). During the cell-depleting treatment, the incidence rate ratio for a relapse was significantly greater in patients with a washout period of 12-17 and > / = 18 weeks compared to the reference period (< 6 weeks). The risk of a relapse was significantly influenced by the occurrence of relapses during FTY treatment and by washout length, with hazard ratios markedly increasing with the washout duration. CONCLUSION: The risk of relapses increases with the washout duration when switching from FTY to lymphocyte-depleting agents.

Recommendations for the management of urinary disorders in multiple sclerosis: a consensus of the Italian Multiple Sclerosis Study Group.

Urinary disorders are uncommon in the initial phases of multiple sclerosis, but increase in frequency as the disease progresses, with a negative impact on quality of life. The goal of this study was to propose a protocol for the diagnosis and treatment of urinary disorders in multiple sclerosis, based on data from the scientific literature and the experience of Italian clinical centres. In particular, the following clinical aspects were considered: what to do with patients with asymptomatic multiple sclerosis; what to do with symptomatic patients; how and when to perform a second-level diagnostic evaluation; and how to treat urinary disorders. A diagnostic-therapeutic algorithm is proposed, that can be applied in Italian clinical centres.

Acute and intermediate toxicity of 3-week radiotherapy with simultaneous integrated boost using TomoDirect: prospective series of 287 early breast cancer patients.

AIMS: To report toxicity of a hypofractionated scheme of whole-breast (WB) intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) to the tumor bed (TB) using Tomotherapy® with Direct modality. METHODS: Patients with early breast cancer, undergoing radiotherapy (RT) in 15 daily fractions to WB (prescription dose 40.05 Gy) and SIB to the TB (48 Gy), between 2013 and 2017, was analyzed. Primary endpoint was acute and intermediate toxicity assessed at the end and within 6 months from RT, according to Radiation Therapy Oncology Group (RTOG) scale. Secondary endpoints included early chronic toxicity at 12-months follow-up, using the Late Effects Normal Tissue Task Subjective, Objective, Management, and Analytic (LENT-SOMA) scale, and cosmesis using Harvard criteria. RESULTS: The study population was of 287 patients. Acute and intermediate toxicity was collected among 183 patients with data available at the end of RT and within 6 months, 85 (46%) experienced G2 toxicity and 84 (46%) G1 toxicity, while 14 (8%) did not report toxicity at any time. A significant reduction of any grade toxicity was observed between the two time points, with the majority of patients reporting no clinically relevant toxicity at 6 months. At univariate analysis, age < 40 years, breast volume > 1000 cm3 and Dmax ≤ 115% of prescription dose were predictive factors of clinically relevant acute toxicity (G ≥ 2) at any time. At multivariable analysis, only age and breast volume were confirmed as predictive factors, with Relative Risks (95% Confidence Intervals): 2.02 (1.13-3.63) and 1.84 (1.26-2.67), respectively. At 12-month follow-up, 113 patients had complete information on any toxicity with 53% of toxicity G < 2, while cosmetic evaluation, available for 102 patients, reported a good-excellent result for 86% of patients. CONCLUSIONS: Hypofractionated WB IMRT with a SIB to the TB, delivered with TomoDirect modality, is safe and well-tolerated. Most patients reported no toxicity after 6 months and good-excellent cosmesis. Predictive factors of clinically relevant toxicity might be considered during treatment planning in order to further reduce side effects.

Oligo metastatic renal cell carcinoma: stereotactic body radiation therapy, if, when and how?

BACKGROUND AND PURPOSE: Renal cell carcinoma (RCC) has traditionally been considered radioresistant with a limited role for conventional fractionation as a local approach. Nevertheless, since the appearance of stereotactic body radiation therapy (SBRT), radiotherapy (RT) has been increasingly employed in the management of metastatic RCC (mRCC). The aim of this study was to evaluate the role of SBRT for synchronous and metachronous oligo metastatic RCC patients in terms of local control, delay of systemic treatment, overall survival and toxicity. PATIENTS AND METHODS: A Monocentric single institution retrospective data collection was performed. Inclusion criteria were: (1) oligo-recurrent or oligo-progressive disease (less than 5 metastases) in mRCC patients after radical/partial nephrectomy or during systemic therapy, (2) metastasectomy or other metastasis-directed, rather than SBRT not feasible, (3) any contraindication to receive systemic therapy (such as comorbidities), (4) all the histologies were included, (5) available signed informed consent form for treatment. Tumor response and toxicity were evaluated using the response evaluation criteria in solid tumors and the Common Terminology Criteria for Adverse Events version 4.03, respectively. Progression-free survival in-field and out-field (in-field and out-field PFS) and overall survival (OS) were calculated via the Kaplan-Meier method. The drug treatment-free interval was calculated from the start of SBRT to the beginning of any systemic therapy. RESULTS: From 2010 to December 2018, 61 patients with extracranial and intracranial metastatic RCC underwent SBRT on 83 lesions. Intracranial and extracranial lesions were included. Forty-five (74%) patients were treated for a solitary metastatic lesion. Median RT dose was 25 Gy (range 10-52) in 5-10 fractions. With a median follow-up of 2.3 years (range 0-7.15), 1-year in-field PFS was 70%, 2-year in-field PFS was 55%. One year out-field PFS was 39% and 1-year OS was 78%. Concomitant systemic therapy was employed for only 11 (18%) patients, for the others 50 (82%) the drug treatment-free rate was 70% and 50% at 1 and 2 years, respectively. No > G1 acute and late toxicities were reported. CONCLUSION: The pattern of failure was pre-dominantly out-of-field, even if the population was negatively selected and the used RT dose could be considered palliative. Therefore, SBRT appears to be a well-tolerated, feasible and safe approach in oligo metastatic RCC patients with an excellent in-field PFS. SBRT might play a role in the management of selected RCC patients allowing for a delay systemic therapy begin (one out of two patients were free from new systemic therapy at 2 years after SBRT). Further research on SBRT dose escalation is warranted.

A diffusion tensor MRI study of cervical cord damage in benign and secondary progressive multiple sclerosis patients.

BACKGROUND: Diffusion tensor (DT) MRI enables quantification of the severity of brain and cervical cord pathology in multiple sclerosis (MS). OBJECTIVE: To investigate DT MRI patterns of cervical cord damage in patients with benign MS (BMS) and secondary progressive MS (SPMS), in order to achieve a better understanding of the mechanisms underlying the development of irreversible disability in MS. METHODS: Conventional and DT MRI scans of the cervical cord and brain were acquired from 40 BMS patients, 28 SPMS patients and 18 healthy individuals. Cervical cord and brain mean diffusivity (MD) and fractional anisotropy (FA) maps were created and average MD and FA were calculated. Cross sectional cord area (CSA) was also computed. RESULTS: 37 (92%) BMS patients and all (100%) SPMS patients had macroscopic cervical cord lesions. Compared with healthy individuals, BMS patients had higher average cord MD while SPMS patients had higher average cord MD, lower average cord FA and lower average CSA. Compared with BMS patients, SPMS patients had lower cord average FA and lower average CSA. In MS patients, Expanded Disability Status Scale (EDSS) was correlated with CSA (r = -0.47, p<0.0001), average cord FA (r = -0.37, p = 0.002) and brain T2 lesion volume (LV) (r = 0.34, p = 0.005). A multivariate regression model identified CSA, average cord FA and brain T2 LV as variables independently influencing the EDSS score (r = 0.58, p<0.0001). CONCLUSIONS: Cervical cord damage outside focal macroscopic lesions is limited in patients with BMS. The assessment of cord and brain pathology provides complementary information to improve the understanding of disability accumulation in MS.

Renewal of the T-cell compartment in multiple sclerosis patients treated with glatiramer acetate.

The immunomodulating activity of glatiramer acetate on T-cells of multiple sclerosis patients has only been partially clarified. The objective of this work was to investigate whether glatiramer acetate modifies thymic release of newly produced T-cells and the peripheral composition of the T-cell repertoire. T-cell receptor excision circles, (thymic) naive (CD4(+)CD45RA(+)CCR7(+)CD31(+)) T helper cells, and central (CD4(+)CD45RA(-)CCR7(+)) and effector (CD4(+)CD45RA(-)CCR7(-)) memory T-cells were evaluated in 89 untreated patients, 84 patients treated for at least 1 year, and 31 patients beginning treatment at the time of inclusion in the study and then followed-up for 12 months; controls were 81 healthy donors. The T-cell repertoire was analysed in selected samples. The percentage of (thymic)naive T helper cells was diminished in untreated patients, but rose to control values in treated subjects; a decrease in central memory T-cells was also observed in treated patients. Follow-up patients could be divided into two subgroups, one showing unmodified (thymic)naive T helper cells and T-cell diversity, the other in which the increased release of new T-cells was accompanied by modifications of the T-cell repertoire. Glatiramer acetate modifies the peripheral T-cell pool by activating a thymopoietic pathway of T-cell release that leads to a different setting of T-cell diversity and, likely, to a dilution of autoreactive T-cells.

Two-year real-life efficacy, tolerability and safety of dimethyl fumarate in an Italian multicentre study.

BACKGROUND: Dimethyl-fumarate (DMF) demonstrated efficacy and safety in relapsing-remitting multiple sclerosis (MS) in randomized clinical trials. OBJECTIVES: To track and evaluate post-market DMF profile in real-world setting. MATERIALS AND METHODS: Patients receiving DMF referred to Italian MS centres were enrolled and prospectively followed, collecting demographic clinical and radiological data. RESULTS: Among the 735 included patients, 45.4% were naïve to disease-modifying therapies, 17.8% switched to DMF because of tolerance, 27.4% switched to DMF because of lack of efficacy, and 9.4% switched to DMF because of safety concerns. Median DMF exposure was 17 months (0-33). DMF reduced the annual relapse rate (ARR) by 63.2%. At 12 and 24 months, 85 and 76% of patients were relapse-free. NEDA-3 status after 12 months of DMF treatment was maintained by 47.5% of patients. 89 and 70% of patients at 12 and 24 months regularly continued DMF. Most frequent adverse events (AEs) were flushing (37.2%) and gastro-enteric AEs (31.1%). CONCLUSION: Our post-market study corroborated that DMF is a safe and effective drug. Additionally, the study suggested that naïve patients strongly benefit from DMF and that DMF improved ARR also in patients who were horizontally switched from injectable therapies due to tolerability and efficacy issues.

Ghrelin secretion in preterm neonates progressively increases and is refractory to the inhibitory effect of food intake.

CONTEXT: Ghrelin, a natural GH secretagogue, is mainly characterized by nonendocrine activities such as orexigenic effect and modulation of the endocrine and metabolic response to variations in energy balance. Ghrelin levels have been reported to be negatively associated with insulin secretion, enhanced in anorexia, and reduced in obesity. Ghrelin levels in newborns were shown to be similar to those found in children and adults without any gender-related difference. OBJECTIVE: The aim of this study was to evaluate ghrelin variations in preterm newborns as a function of fasting and feeding. METHODS: To this end, in 31 preterm neonates (13 males and 18 females) categorized as appropriate for gestational age, total ghrelin levels were measured in cord blood and then on the fourth day of life before and after meals. RESULTS: Ghrelin levels in cord blood [(median 25th-75th centile) 184; 122-275 pg/ml] were higher (P < 0.006) than levels measured in the mothers at delivery (167.0; 89-190 pg/ml). In newborns on the fourth day of life, ghrelin levels in fasting conditions (451; 348-649 pg/ml) were higher (P < 0.0004) than those in cord blood. The meal did not at all modify ghrelin levels (476; 302-775 pg/ml), which were unchanged, compared with those in fasting condition. Total ghrelin levels in cord blood were not associated with weight and length; conversely, on the fourth day of life ghrelin levels in newborns were negatively correlated to birth weight as well as the present weight (P = 0.05, r = -0.4). Ghrelin levels were independent of gender, type of delivery, and the kind of feeding regimen. CONCLUSIONS: The secretion of total ghrelin increases from delivery to the fourth day of life when it is refractory to the inhibitory effect of food intake, but it is negatively correlated to body weight.

Molecular characterisation of two human cancer cell lines selected in vitro for their chemotherapeutic drug resistance to ET-743.

ET-743 (Yondelis(TM), Trabectedin) isolated from the tunicate Ecteinascidia turbinata, is being tested in phase II clinical trials in Europe and the United States of America (USA). Studies with different solid tumours have shown antitumour activity in advanced, pre-treated sarcomas as well as in drug-resistant breast and ovarian cancer. The primary mechanism of action for ET-743 has not been fully elucidated and different models have been suggested to explain its molecular mechanism of action. ET-743 binds tightly to the minor groove of DNA and previous data have suggested that ET-743 acts by interfering with RNA transcription. To further investigate the mechanism of in vitro drug resistance, we evaluated the gene expression profile in ovarian and chondrosarcoma cell lines selected for resistance to ET-743. We found 70 genes whose expression was modulated in both drug-resistant cell lines when compared with their respective parental drug-sensitive cell lines. This pattern of gene expression seems to be selective for ET-743-resistant cells, since ovarian cancer cells resistant to paclitaxel did not share the same gene expression changes. Data presented in this study reveal different molecular pathways that could be involved in the cellular mechanism of ET-743 resistance.

[Sleeping in the supine position in the ASL 11 region of Piemonte. Assessment of the efficacy of a promotional campaign]. / Dormire sulla schiena nell'asl 11--regione Piemonte Valutazione dell'efficacia di una campagna promozionale.

OBJECTIVES: To record the prevalence of the sleeping position of sucklings living in the ASL 11-Regione Piemonte; to make an information campaign about the utility of sleeping in the supine position (most important protection factor against the SIDS); to find out its efficacy for a short or long time. METHODS: During the first two months of 2002 all the parents coming to the consulting rooms for the compulsory vaccinations of their 3 and 5 months old babies have been interviewed about the position of their babies during sleep. The same recording has been made in the first two months of 2003 and 2004. During 2002 various consciousness campaigns have been made, above all for medical operators of hospital nurseries and of Mother-and-Child Departments and Prevention Departments in ASL 11 area. RESULTS: Before the consciousness campaign the percentage of 3 months old sucklings sleeping in the supine position was 62,3% and 55% for the 5 months old suckings; after the campaign the percentage has grown to 77,4% for 3 months old sucklings and 74,5% for 5 months old sucklings during 2003 and during 2004 the percentage has grown to 80,3% and 74,2%, respectively. CONCLUSIONS: A simple and not expensive but capillary consciousness and information campaign addressed to medical operators has obtained valid and statistically relevant results in a short time.

Thyroid function and autoimmunity during interferon beta-1b treatment: a multicenter prospective study.

Thyroid dysfunction and autoimmunity have been reported during type I interferon therapy, namely interferon-alpha for chronic hepatitis or interferon-beta for multiple sclerosis. To define the frequency of thyroid dysfunction and autoimmunity during interferon-beta treatment, 156 multiple sclerosis patients were prospectively followed up by 18 centers for 1 yr after starting interferon-beta-1b treatment. Serial clinical assessments and tests of thyroid and liver function and antithyroid autoantibodies (all performed by the same centralized laboratory) were conducted every 3 months. TSH and antithyroid autoantibodies against human TG or thyroid microsomal antigens were measured by immunoradiometric methods; free T3 and T4 were measured by chromatographic assays. Longitudinal occurrence of thyroid or liver alterations or of autoantibodies was analyzed with the generalized estimating equations method, correcting for the correlation of repeated measurements of the same subject over time. Pretreatment comparison with a control group of 437 healthy blood donors did not show significant differences in the frequency of thyroid dysfunction or antithyroid autoantibody positivity. During interferon-beta treatment, the de novo frequency of thyroid alteration was 8.3%, that of liver alteration was 37.5%, and that of antithyroid autoantibody was 4.5%. Generalized estimating equations analysis demonstrated that the frequency of liver alteration significantly increased during treatment compared with the baseline value (odds ratio, 7.03; confidence interval, 2.49-19.9), whereas that of thyroid alteration or of antithyroid autoantibodies did not. The frequency of thyroid dysfunction during interferon-beta treatment showed random, nonsignificant changes over time and, in addition, was not correlated to antithyroid autoantibody positivity.

Evidence of linkage between susceptibility to multiple sclerosis and HLA-class II loci in Italian multiplex families.

To verify whether multiallelic polymorphisms belonging to HLA class II genes are linked to multiple sclerosis (MS) in the Italian population, we studied 28 multiplex MS families originating from different areas of Italy. Allelic characterization was carried out by analysis of RFLPs and oligonucleotide typing. Evidence supporting the existence of linkage between MS susceptibility and the HLA class II loci DRB1, DQA1 and DQB1 was provided using two non-parametric tests, affected sib-pair analysis, and affected-pedigree-member (APM) analysis. The APM analysis also suggested the existence of genetic heterogeneity for the HLA class II loci and MS susceptibility in our series. Linkage disequilibrium between MS susceptibility and the haplotype DRB1*1501,DQA1*0102,DQB1*0602 was demonstrated by applying the transmission linkage disequilibrium test to our families. Finally, lod score analysis suggests that in our Italian families, MS susceptibility is conferred by HLA class II alleles according to a low-penetrance autosomal recessive mode of inheritance.

Autoantibodies in multiple sclerosis patients before and during IFN-beta 1b treatment: are they correlated with the occurrence of autoimmune diseases?

Autoimmune side effects, namely autoantibody (autoAb) occurrence and thyroid function alteration, have been described during interferon-beta (IFN-beta) treatment for multiple sclerosis (MS). AutoAb occurrence and autoimmune thyroid diseases are also frequently detected in MS patients free of any treatment. The aim of this study was to evaluate the relationship between IFN-beta 1b treatment, autoAb occurrence, and autoimmune diseases in MS. Thyroid and liver function and serum autoAb (antithyroid, antinuclear, anti-liver, anti-kidney microsomes, anti-smooth muscle and parietal cell antigens) occurrence were evaluated in 156 relapsing-remitting MS (RRMS) patients before and every 3 months after starting IFN-beta 1b treatment (8 MIU subcutaneously [s.c.] on alternate days). The probability of having liver or thyroid function alteration or autoAb occurrence was analyzed longitudinally with the generalized estimating equations (GEE) approach. At baseline, 16.1% of patients had autoAb. During treatment, autoAb occurred de novo in 7.2% of patients. GEE analysis showed that the probability of having autoAb at any time during IFN-beta 1b treatment did not change significantly compared with baseline. AutoAb occurring de novo rarely persisted during treatment and significantly less than those already present at baseline. Positivity for autoAb at baseline or during treatment was not correlated with the development of thyroid or liver function alteration during IFN-beta 1b treatment. Our study indicates that IFN-beta treatment is a safe treatment for MS patients, free of risk of autoimmunity and of associated liver or thyroid function alteration.

Cerebral involvement in celiac disease: a serial MRI study in a patient with brainstem and cerebellar symptoms.

A patient with celiac disease and relapsing-progressive symptoms suggesting brainstem and cerebellar involvement underwent serial MRIs. The first examination revealed multiple enhancing and nonenhancing lesions. Thereafter, a large enhancing cerebellar lesion appeared, followed by severe cerebellar atrophy. The presence of structural neuronal damage was confirmed by proton MR spectroscopy and magnetization transfer imaging. MRI results and CSF findings suggested that neurologic complications were more likely due to an inflammatory process.

Liver and thyroid function and autoimmunity during interferon-beta 1b treatment for MS.

BACKGROUND: The occurrence or recurrence of autoimmune diseases or of autoantibodies (autoAb) has been reported during type I interferon (IFN) treatment. OBJECTIVE: To define the frequency of thyroid and liver dysfunction and of autoimmunity during IFN-beta 1b (IFNB) treatment of MS. METHODS: Prospective 1-year multicenter follow-up of 156 patients with MS recruited by 18 centers was conducted. Thyroid-stimulating hormone and anti-thyroid autoAb were measured by an immunoradiometric method, thyroid hormones by chromatographic assay, and non-organ-specific autoAb by indirect immunofluorescence. Tests were repeated every 3 months. The probability of having liver, thyroid, or autoAb alterations was analyzed longitudinally with the generalized estimating equations (GEE) method. RESULTS: Thyroid dysfunction was observed in 5.3% of cases at baseline and 8.3% de novo during IFNB treatment. GEE analysis showed that the probability of having thyroid alteration did not change significantly during treatment compared with baseline. Liver alteration was observed in 4.6% of cases at baseline and 37.5% de novo during IFNB treatment (p < 0.0001). GEE analysis showed that the probability of having liver alteration was higher (p < 0.002) at months 3 and 6 compared with baseline, returning to values similar to baseline by month 9. AutoAb were detected in 16.1% of patients at baseline and in 20% during IFNB. GEE analysis showed that the probability of having autoAb did not change significantly during treatment compared with baseline. Thyroid or liver alteration or autoAb occurring de novo during IFNB were usually transient. CONCLUSIONS: Differently from the frequency of liver function alteration (which significantly increased during the first months of IFNB treatment, suggesting a probable causal relationship with IFNB), the frequency of thyroid dysfunction or of autoimmunity showed random and insignificant changes over time, probably not related to IFNB treatment.

Effect of glatiramer acetate on MS lesions enhancing at different gadolinium doses.

This baseline-vs-treatment study of 20 patients with relapsing-remitting MS investigated whether glatiramer acetate (GA) has a graduated effect on MS inflammatory activity, which was measured using monthly, standard, and triple dose gadolinium (Gd)-enhanced MRI. GA significantly reduced the mean numbers of enhancing lesions/patient/month on both standard dose and triple dose scans, without interactions with the Gd dose. GA is effective in reducing MS activity, independent of the severity of the MRI-detectable inflammatory process.

Relevance of interleukin 1 receptor antagonist intron 2 polymorphism in Italian MS patients.

The A1/A1 genotype of the anti-inflammatory cytokine interleukin 1 receptor antagonist (IL-1Ra) polymorphism was more frequent in 339 Italian MS patients than in healthy controls (HCs) (odds ratio = 1.83). A more aggressive disease course was also associated with A1+ genotypes and might reflect the reduced ability of mononuclear cell cultures of A1+ HCs to produce IL-1Ra. We conclude that an IL-1Ra gene polymorphism is associated with occurrence of disease and clinical course variability in Italian MS patients.