Is silver diammine fluoride effective in arresting dental caries in cavitated primary molars?

CLINICAL QUESTION: To evaluate the efficacy of silver diamine fluoride (SDF) in arresting dental caries in cavitated caries lesions in primary molars. DATA SOURCES: A systematic search was carried out in PubMed, Scopus, and Embase. Furthermore, cross-referencing was performed using the references lists of full-text articles and grey literature was also retrieved for eligible studies. Two independent reviewers were responsible for study selection and data extraction. STUDY SELECTION: Randomized and non-randomized clinical studies that evaluated the caries arrest rate of SDF compared to no treatment or any other type of non-invasive or minimally-invasive treatment were included. Only publications in the English, Italian and French language and with a minimum follow-up of 6 months were considered for study eligibility. DATA EXTRACTION AND SYNTHESIS: The characteristics of the included studies-age, sex, type of study, sample size, caries at baseline, setting, operator, blinding, intervention, outcomes and assessment of any confounders-were extracted from the included papers. The quality assessment was carried out using the Cochrane risk of bias tool. The success rate and odds ratios were chosen to calculate the effect size for the meta-analysis. RESULTS: A total of nine publications were included for qualitative review and five of them were included in the meta-analysis. Around half of lesions that received annual or biannual application SDF ≥ 38% were arrested. CONCLUSIONS: SDF 38% application was found to be effective in arresting dental caries progression in cavitated primary molars.

Pathways between Social Capital and Oral Health from Childhood to Adolescence.

This study aimed to evaluate the theoretical pathways by which social capital can influence dental caries and oral health-related quality of life (OHRQoL) of children over time. This 10-y prospective cohort started in 2010 with a sample of 639 preschoolers aged 1 to 5 y from the southern Brazil. Community and individual social capital were assessed at baseline through the presence of formal institutions in the neighborhood and social networks, respectively. In the 10-y follow-up, the individual social capital was evaluated by social trust and social networks. Dental caries was measured by the International Caries Detection and Assessment System (ICDAS), and the short version of the Child Perception Questionnaire (CPQ11-14) was used to assess OHRQoL. Demographic, socioeconomic, behavioral (frequency of toothbrushing and use of dental services), and psychosocial (sense of coherence) characteristics were also assessed. Structural equation modeling was used to evaluate the associations between variables over time. About 429 children were reassessed at 10-y follow-up (67.1% cohort retention rate). High community social capital at baseline directly predicted lower occurrence of dental caries and better OHRQoL after 10 y. Social capital at community level also indirectly predicted lower occurrence of dental caries through sense of coherence, frequency of toothbrushing, and use of dental services. Individual social capital at follow-up was indirectly linked to OHRQoL via the psychosocial pathway (sense of coherence). Community-level social capital was associated with dental caries and OHRQoL over time. The relationship between individual social capital and oral health was mediated through the psychosocial pathway.

A retrospective clinical study on the resin infiltration of proximal caries lesions: the operator's effect.

PURPOSE: This retrospective university-based study investigated the effect of operators' training and previous experience on the success of resin infiltration (RI) in arresting proximal non-cavitated caries lesions in primary and permanent teeth. METHODS: Information was collected regarding RI of proximal non-cavitated caries lesions in primary and permanent teeth with a follow-up period up to 32 months. Factors investigated were: operators' clinical experience and training, patient's age, tooth, arch, mouth-side, surface treated, tooth separation, and baseline lesion depth. Kaplan-Meier survival and Cox regression analysis with shared frailty were used (α = 5%). RESULTS: A total of 130 proximal surfaces treated on 115 teeth of 43 children (11 ± 4.4 years) were evaluated. Survival of RI was 46% up to 32 months. Lesions treated by non-trained dentists were more likely-to-present progression than those performed by non-trained dental students under supervision (HR 2.41, 95% CI: 1.00-5.80); conversely, no difference was found between non-trained dental students under supervision and trained dentists (HR 0.52, 95% CI: 0.16-1.70). Additionally, dentin lesions were 59% more-likely-to-present progression than enamel lesions (HR 0.41, 95% CI: 0.17-0.99). CONCLUSION: The operator's experience and training could influence the success of RI on proximal non-cavitated caries lesions and it should be taken into consideration when choosing this treatment modality.

The Hall Technique 10 years on: Questions and answers.

It is ten years since the first paper on the Hall Technique was published in the British Dental Journal and almost 20 years since the technique first came to notice. Dr Norna Hall a (now retired) general dental practitioner from the north of Scotland had, for many years, been managing carious primary molar teeth by cementing preformed metal crowns over them, with no local anaesthesia, tooth preparation or carious tissue removal. This first report, a retrospective analysis of Dr Hall's treatments, caused controversy. How could simply sealing a carious lesion, with all the associated bacteria and decayed tissues, possibly be clinically successful? Since then, growing understanding that caries is essentially a biofilm driven disease rather than an infectious disease, explains why the Hall Technique, and other 'sealing in' carious lesion techniques, are successful. The intervening ten years has seen robust evidence from several randomised control trials that are either completed or underway. These have found the Hall Technique superior to comparator treatments, with success rates (no pain or infection) of 99% (UK study) and 100% (Germany) at one year, 98% and 93% over two years (UK and Germany) and 97% over five years (UK). The Hall Technique is now regarded as one of several biological management options for carious lesions in primary molars. This paper covers commonly asked questions about the Hall Technique and speculates on what lies ahead.

Structural, magnetic and electrical properties of SrRuO3 films and SrRuO3/SrTiO3 superlattices.

SrRuO3 films and SrRuO3/SrTiO3 superlattices grown on SrTiO3(001) were studied by structural, magnetic, magnetoresistance and Hall effect measurements. The superlattices showed heteroepitaxial growth with coherent interfaces and a Ru/Ti diffusion region of 1-1.5 unit cells. The resistivity had metallic character above a critical thickness of 3-4 unit cells, becoming insulating below. There was no hint of conduction processes along the interfaces. Both magnetization and magnetoresistance measurements showed an increase of the magnetic anisotropy, consistent with magnetostriction effects. The magnetostriction coefficient was estimated as λ100 âˆ¼ 1.4 × 10(-4). Three unit cell thick SrRuO3 layers in SrRuO3/SrTiO3 superlattices were found to have tetragonal crystal symmetry, as deduced from the sign change of the anomalous Hall constant.

Dendritic cell, monocyte and T cell activation and response to glatiramer acetate in multiple sclerosis.

BACKGROUND: Treatment with glatiramer acetate (GA) modestly decreases disease activity in multiple sclerosis (MS). The mechanism of action is incompletely understood and differences in the response to treatment between individuals may exist. OBJECTIVE: To study the activation of CD4+ T cells, monocytes and dendritic cells (DC) in relation to disease activity in MS patients treated with GA. METHODS: Flow cytometry was used to study the activation of CD4+ T cells and T cell subsets (CD25(high) and CD26(high) cells), monocytes and DCs in a cross-sectional study of 39 untreated and 29 GA-treated MS patients, the latter followed prospectively for one year. Gd-enhanced magnetic resonance imaging (MRI) studies were conducted in all patients. Disease activity was assessed as relapses. RESULTS: The median percentage of DCs expressing CD40 was 10% in untreated MS patients and 5.9% in GA-treated patients (Bonferroni-corrected p=0.0005). The hazard ratio of relapse was 1.32 (95% confidence interval 1.05-1.64) per 1% increase in CD40+ DCs. Patients treated with GA had fewer CD4+ T cells expressing surface markers associated with T helper type 1 effector responses and more CD4+ T cells expressing surface markers associated with regulatory, naïve or central memory T cell populations, but CD4+ T cell activation was not related with relapse risk. CONCLUSIONS: MS patients treated with GA show prominent changes in circulating antigen-presenting cells and CD4+ T cells. Expression of CD40 on DCs is significantly lower and associated with relapse risk in MS patients treated with GA.

Stabilization of ferromagnetic order in La(0.7)Sr(0.3)MnO3-SrRuO3 Superlattices.

The study of spatially confined complex oxides is of wide interest, since correlated electrons at interfaces might form exotic phases. Here La(0.7)Sr(0.3)MnO(3)/SrRuO(3) superlattices with coherently grown interfaces were studied by structural techniques, magnetization, and magnetotransport measurements. Magnetization measurements showed that ferromagnetic order in ultrathin La(0.7)Sr(0.3)MnO(3) layers is stabilized in the superlattices down to layer thicknesses of at least two unit cells. This stabilization is destroyed, if the ferromagnetic layers are separated by two unit cell thick SrTiO(3) layers. The resistivity of the superlattices showed metallic behavior and was dominated by the conducting SrRuO(3) layers, the off-diagonal resistivity showed an anomalous Hall effect from both SrRuO(3) and La(0.7)Sr(0.3)MnO(3) layers. This shows that the La(0.7)Sr(0.3)MnO(3) layers are not only ferromagnetic but also highly conducting; probably a conducting hole gas is induced at the interfaces that stabilizes the ferromagnetic order. This result opens up an alternative route for the fabrication of two-dimensional systems with long-range ferromagnetic order.

Reversible electrical switching of spin polarization in multiferroic tunnel junctions.

Spin-polarized transport in ferromagnetic tunnel junctions, characterized by tunnel magnetoresistance, has already been proven to have great potential for application in the field of spintronics and in magnetic random access memories. Until recently, in such a junction the insulating barrier played only a passive role, namely to facilitate electron tunnelling between the ferromagnetic electrodes. However, new possibilities emerged when ferroelectric materials were used for the insulating barrier, as these possess a permanent dielectric polarization switchable between two stable states. Adding to the two different magnetization alignments of the electrode, four non-volatile states are therefore possible in such multiferroic tunnel junctions. Here, we show that owing to the coupling between magnetization and ferroelectric polarization at the interface between the electrode and barrier of a multiferroic tunnel junction, the spin polarization of the tunnelling electrons can be reversibly and remanently inverted by switching the ferroelectric polarization of the barrier. Selecting the spin direction of the tunnelling electrons by short electric pulses in the nanosecond range rather than by an applied magnetic field enables new possibilities for spin control in spintronic devices.

Glatiramer acetate antibodies, gene expression and disease activity in multiple sclerosis.

BACKGROUND: Glatiramer acetate (GA) treatment suppresses disease activity in multiple sclerosis (MS). The immunological response to treatment may differ in patients who are stable on GA therapy and patients with breakthrough disease activity, but the results of previous studies are inconsistent. OBJECTIVES: We studied the immunological response to GA and its relationship with disease activity. METHODS: Anti-GA antibodies in plasma and the expression of genes encoding cytokines and T-cell-polarizing transcription factors in blood cells were analysed by flow cytometric bead array and polymerase chain reaction (PCR) analysis in 39 untreated and 29 GA-treated relapsing-remitting MS patients. Definition of breakthrough disease was based on the occurrence of relapses, disability progression, or gadolinium (Gd)-enhanced MRI. RESULTS: The expression of T helper type 1 (Th1) and Th17 cytokines and transcription factors was reduced during long-term treatment, but there was no relationship between the expression of cytokines and transcription factors and anti-GA antibodies. High expression of mRNA encoding GATA3 and lymphotoxin-ß (LT-ß) was associated with low disease activity in Gd-enhanced MRI studies. None of the variables studied were associated with clinical disease activity. GA treatment resulted in the development of IgG and IgG4 anti-GA antibodies during the first months of treatment, persisting during long-term treatment. CONCLUSIONS: The observed relationship between the expression of mRNA encoding GATA3 and LT-ß expression and MRI disease activity deserves further analysis in future studies. The development of anti-GA antibodies was observed in all patients treated with GA, but this was not related with measures of cellular immunity, clinical or MRI disease activity.

Disease protection and interleukin-10 induction by endogenous interferon-ß in multiple sclerosis?

OBJECTIVE: An immune activation response resembling virus or type I interferon responses has been observed in untreated multiple sclerosis (MS), but its pathogenic significance is uncertain. We studied the relationship between a type I interferon-like response in untreated patients with MS and disease activity. METHODS: Gene expression was analyzed by real-time reverse transcriptase polymerase chain reaction (PCR) in whole blood samples and by microarray analysis of mononuclear cells from untreated patients with MS, patients with MS treated with IFN-ß, and patients with MS with anti-IFN-ß neutralizing antibodies (NAb). Disease activity was assessed by gadolinium-enhanced magnetic resonance imaging. RESULTS: Eight of 36 untreated patients with MS had spontaneously increased expression of the type I IFN-induced gene MX1. Microarray gene expression analysis demonstrated that patients with increased spontaneous MX1 expression also had increased expression of other genes induced by regular IFN-ß treatment of MS. MX1 expression correlated with FOXP3 and IL10 expression, and IL10 expression correlated negatively with disease activity on magnetic resonance imaging. Further, in vivo IL10 expression was lower in NAb-positive patients than in untreated patients with MS and healthy controls. Finally, ex vivo treatment of mononuclear blood cells with IFN-ß induced the expression of IL10, and this was blocked by the addition of serum from NAb-positive patients with MS. CONCLUSION: Our findings suggest that endogenous IFN-ß may induce the expression of immunoregulatory IL10 in MS and that this might be associated with dampening of inflammatory disease activity.

Tailoring magnetic interlayer coupling in La0.7Sr0.3MnO3/SrRuO3 superlattices.

The magnetic interlayer coupling in La0.7Sr0.3MnO3/SrRuO3 superlattices was investigated. High quality superlattices with ultrathin La0.7Sr0.3MnO3 and SrRuO3 layers were fabricated by pulsed laser deposition. The superlattices grew coherently with Mn/Ru intermixing restricted to about one interfacial monolayer. Strong antiferromagnetic interlayer coupling depended delicately on magnetocrystalline anisotropy and intermixing at interfaces. Ab initio calculations elucidated that the antiferromagnetic coupling is mediated by the Mn-O-Ru bond. The theoretical calculations allowed for a quantitative correlation between the total magnetic moment of the superlattice and the degree of Mn/Ru intermixing.

Breakthrough disease during interferon-[beta] therapy in MS: No signs of impaired biologic response.

BACKGROUND: Disease activity is highly variable in patients with multiple sclerosis (MS), both untreated and during interferon (IFN)-beta therapy. Breakthrough disease is often regarded as treatment failure; however, apart from neutralizing antibodies (NAbs), no blood biomarkers have been established as reliable indicators of treatment response, despite substantial, biologically measurable effects. We studied the biologic response to treatment in a cohort of NAb-negative patients to test whether difference in responsiveness could segregate patients with and without breakthrough disease during therapy. METHODS: Gene expression in blood cells from 23 patients with relapsing-remitting MS was analyzed by microarray and PCR. Samples were collected pretreatment and 9-12 hours after IFNbeta injection at 3 and 6 months' treatment. Definition of breakthrough disease was based on the occurrence of relapses, disability progression, or subclinical activity on 3T MRI at 3 and 6 months. RESULTS: Sixteen patients had breakthrough disease and 7 patients were stable. Microarray and PCR showed marked effects of IFNbeta on gene expression profiles, but biologic responses did not differ between patients with breakthrough disease and stable patients. However, pretreatment variables did differ: patients with breakthrough disease had lower baseline IL10 expression, more gadolinium-enhancing lesions, and a higher number and volume of T2 lesions. CONCLUSIONS: Breakthrough disease during interferon (IFN)-beta treatment is not paralleled by differences in biologic responsiveness to treatment in NAb-negative patients; most likely, the spontaneously occurring variation in underlying disease activity between patients causes the varying level of breakthrough disease observed in IFNbeta-treated patients with multiple sclerosis.

Increased urinary orosomucoid excretion predicts preeclampsia in pregnant women with pregestational type 1 diabetes.

AIMS: We evaluated the urinary orosomucoid excretion (UOE) as a biomarker of preeclampsia and preterm delivery in pregnant women with type 1 diabetes. METHODS: Singleton pregnant women with pregestational type 1 diabetes were included provided one urine sample had been collected before 17 gestational weeks. Serum and urinary orosomucoid were analysed by immunoturbidimetry. Primary outcome measurements were development of preeclampsia (blood pressure>140/90mmHg and proteinuria) and preterm delivery before 37 weeks. RESULTS: In total 173 women were included. The UOE increased during pregnancy. Preeclampsia developed in 20 women and 65 women delivered preterm. Using logistic regression analysis we found that UOE>1.37mg/l (OR: 6.85 (95% CI: 1.97-23.88; p<0.003)), nulliparity (3.88 (1.10-13.72); p<0.04), systolic blood pressure>120mmHg (4.12 (1.35-12.59); p<0.02) and duration of diabetes>20 years (3.69 (1.18-11.52); p<0.03) independently predicted the development of preeclampsia. Independent predictors of preterm delivery were duration of diabetes and HbA1c>7%. The remaining covariates included in the regression models were BMI, serum creatinine, smoking and microalbuminuria. CONCLUSIONS: Increased UOE early in pregnancy predicted preeclampsia in women with pregestational type 1 diabetes independently of albuminuria and other known risk factors. No association to preterm delivery was found.

Absence of MxA induction by interferon beta in patients with MS reflects complete loss of bioactivity.

BACKGROUND: In patients with multiple sclerosis (MS), neutralizing antibodies (NAbs) appearing during treatment with interferon (IFN) beta reduce or in high concentrations abolish bioactivity and therapeutic efficacy. In vivo MxA induction by IFNbeta is used as a marker of biologic response to IFNbeta. It has been argued that despite absence of MxA induction measured by PCR, some bioactivity might be preserved. In a cohort study, we measured gene expression by gene chip analysis in NAb-negative and NAb-positive patients to test that hypothesis. METHODS: The effect of IFNbeta was studied by comparing samples collected before and 9-12 hours after an injection. The cohort consisted of 12 NAb-positive patients without MxA response and 12 NAb-negative patients with preserved response. MxA in vivo response was determined in whole blood using real-time PCR. Screening for IFNbeta-regulated genes in mononuclear cells was done using gene chips. False discovery rate (FDR) analysis was used as statistical tool. RESULTS: Of 8,793 genes, 5,593 were detectable in at least one patient in both groups. Of these, calculation of FDR revealed 1,077 IFNbeta-regulated genes at a 5% level in NAb-negative patients. The corresponding number of IFNbeta-regulated genes in NAb-positive patients was zero. CONCLUSION: In neutralizing antibody (NAb)-positive patients without an MxA response, we were not able to detect differential expression of any of the 1077 interferon (IFN) beta-regulated genes identified in NAb-negative patients. Lack of MxA in vivo response in patients with multiple sclerosis with NAbs is a reliable marker of a completely blocked biologic response to IFNbeta, with no indication of residual bioactivity.

Identification of new sensitive biomarkers for the in vivo response to interferon-beta treatment in multiple sclerosis using DNA-array evaluation.

OBJECTIVE: Neutralizing antibodies (NAbs) occur in a proportion of multiple sclerosis (MS) patients treated with interferon (IFN)-beta. NAbs impair the effect of treatment. The biological effect of IFN-beta can be measured as the induction of the myxovirus resistance protein A (MxA) molecule. However, other markers could be more sensitive for evaluating the response to IFN-beta. We used DNA array analysis to identify genes that are strongly induced in blood cells by IFN-beta, and measured their expression in MS patients with different NAb levels. METHODS: Gene expression was studied on DNA arrays in untreated patients, in NAb negative patients, and in MS patients with varying NAb levels 9-12 h and 36-48 h after IFN-beta administration. The expression of selected genes was measured by real-time PCR. NAb levels were assessed by a cytopathic effect assay. RESULTS: Several hundred genes were induced 9-12 h after an injection of IFN-beta. The molecules CXCL10, CCL2 and IFI27 were among the most strongly induced. Gene induction was generally much less pronounced after 36-48 h, but IFI27 remained strongly induced. The strong induction of these molecules and MxA was confirmed by real-time PCR. Induction of MxA, CCL2, CXCL10 and IFI27 was reduced in patients with low NAb levels and lost in patients with intermediate/high NAb levels. CONCLUSION: We identify IFI27, CCL2 and CXCL10 as sensitive biomarkers for the response to IFN-beta. The expression of these markers adequately reflects bioactivity of IFN-ss as documented by the decreased induction in low NAb-positive patients and the lost induction in patients with moderate/high NAb levels.

Emergency department-initiated tobacco control: a randomised controlled trial in an inner city university hospital.

OBJECTIVES: Emergency department (ED) patients show high smoking rates. The effects of ED-initiated tobacco control (ETC) on 7-day abstinence at 12 months were investigated. METHODS: A randomised controlled intention-to-treat trial (trials registry no.: ISRCTN41527831) was conducted with 1044 patients in an urban ED. ETC consisted of on-site counselling plus up to four telephone booster sessions. Controls received usual care. Analysis was by logistic regression. RESULTS: In all, 630 (60.7%) participants were males, the median age was 30 years (range 18-81) and the median smoking intensity was 15 (range 1-60) cigarettes per day. Overall, 580 study participants (55.6%) were unmotivated, 331 (31.7%) were ambivalent and 133 (12.7%) were motivated smokers. ETC (median time 30 (range 1-99) min) was administered to 472 (91.7% out of 515) randomised study participants. At follow-up, 685 study participants (65.6% of 1044) could be contacted. In the ETC group, 73 out of 515 (14.2%) in the ETC group were abstinent, whereas 60 out of 529 (11.3%) controls were abstinent (OR adjusted for age and gender = 1.31 (95% CI 0.91 to 1.89, p = 0.15). Stratified for motivation to change behaviour, the adjusted ORs for ETC versus usual care were OR = 1.00 (95% CI 0.57 to 1.76) in unmotivated smokers, respectively OR = 1.37 (95% CI 0.73 to 2.58) in ambivalent smokers and OR = 2.19 (95% CI 0.98 to 4.89) in motivated smokers, p for trend = 0.29. CONCLUSIONS: ETC, in the form of on-site counselling with up to four telephone booster sessions, showed no overall effect on tobacco abstinence after 12 months. A non-significant trend for a better performance of ETC in more motivated smokers was observed.

Effect of a single dislocation in a heterostructure layer on the local polarization of a ferroelectric layer.

We study, on an atomic scale, the influence of a single dislocation in a SrTiO3 sublayer on the local ferroelectric polarization of the neighboring ferroelectric PbZr0.2Ti0.8O3 (PZT) sublayer in an epitaxial SrTiO3/PbZr0.2Ti0.8O3/SrTiO3 three-layer heterostructure. The strain field of the dislocation in the SrTiO3 layer propagates across the interface into the PZT layer and leads to a strong variation of the c-lattice parameter of the PZT layer. Accompanying a strong reduction of the c-lattice parameter, the off-center displacements of the Zr/Ti atoms away from the center of the oxygen octahedra are also strongly decreased, resulting in a decrease of the local spontaneous polarization by up to 48%.

Elastic strain at interfaces and its influence on ionic conductivity in nanoscaled solid electrolyte thin films--theoretical considerations and experimental studies.

Ionic transport in solids parallel to grain or phase boundaries is usually strongly enhanced compared to the bulk. Transport perpendicular to an interface (across an interface) is often much slower. Therefore in modern micro- and nanoscaled devices, a severe influence on the ionic/atomic transport properties can be expected due to the high density of interfaces.Transport processes in boundaries of ionic materials are still not understood on an atomic scale. In most of the studies on ionic materials the interfacial transport properties are explained by the influence of space charge regions. Here we discuss the influence of interfacial strain at semicoherent or coherent heterophase boundaries on ionic transport along these interfaces in ionic materials. A qualitative model is introduced for (untilted and untwisted) hetero phase boundaries. For experimental verification, the interfacial oxygen ionic conductivity of different multilayer systems consisting of cubic ZrO(2) stabilised by aliovalent dopands (YSZ, CSZ) and an insulating oxide is investigated as a function of structural mismatch. Recent results on extremely fast ionic conduction in YSZ/SrTiO(3) thin film systems ("colossal ionic concuctivity at interfaces") is discussed from the viewpoint of strain effects.

Vortex polarization states in nanoscale ferroelectric arrays.

Two-dimensional arrays of ferroelectric lead zirconate titanate (PZT) nanodots were fabricated using pulsed laser deposition through ultrathin anodic aluminum oxide membrane stencil masks. The static distribution of polarization configurations was investigated using in- and out-of-plane piezoresponse force microscopy (PFM). The observed presence of an in-plane polarization component in nominally (001) oriented PZT suggests the existence of a significant deviation from the regular tetragonal structure that allows the formation of complex core-polarization states. Core-polarization states may indicate the presence of quasi-toroidal polarization ordering. The experimental results are compared with a theoretical model to determine the fingerprint of a vortex polarization state in PFM.

Treatment with azathioprine and cyclic methylprednisolone has little or no effect on bioactivity in anti-interferon beta antibody-positive patients with multiple sclerosis.

BACKGROUND: It is unknown whether immunosuppression of patients who have developed interferon-beta (IFN-beta) neutralizing antibodies (NAbs) hastens disappearance of NAbs in the blood. OBJECTIVE: We wanted to test whether immunosuppression with cyclic methylprednisolone (MP) in combination with azathioprine (AZA) for 6 months accelerates recovery of IFN-beta bioactivity in patients with multiple sclerosis (MS) with abolished in-vivo myxovirus resistance protein A (MxA) mRNA response to IFN-beta. METHODS: We included 13 patients with MS with NAbs and a low IFN-beta bioavailability detected by the MxA-mRNA response in a descriptive, non-randomized trial. Another 14 NAb-positive patients with a low MxA-mRNA response served as controls. The primary outcome was the fraction of patients who regained an MxA-mRNA response to IFN-beta. NAbs were measured by means of a clinically validated cytopathic effect assay and a new reporter gene assay. The in-vivo MxA-mRNA response was measured by real-time polymerase chain reaction. RESULTS: A total of 11 patients in the treatment group completed the trial. In all, two of these 11 patients regained an in-vivo MxA-mRNA response as compared to one of 14 patients in the control group. CONCLUSION: Treatment with AZA and cyclic MP for 6 months has little or no effect on IFN-beta bioactivity in NAb-positive patients with MS.