Biomedical subjects

R Egg

Publications and source records attributed to R Egg.

9 recordsLinked to original sources

PubMed2006

Interferon-beta antibodies have a higher affinity in patients with neutralizing antibodies compared to patients with non-neutralizing antibodies.

In this study, we investigated the affinity, determined by a relative affinity assay, using increasing concentrations of sodium-isothiocyanate to disrupt the antigen antibody binding of neutralizing and non-neutralizing antibodies against interferon-beta (IFNbeta)-1a and -1b in 73 serum samples of MS patients treated with IFNbeta-1a or -1b. Relative affinity values were significantly higher in NAB-positive compared to NAB-negative samples and in samples of IFNbeta-1a-treated patients compared to IFNbeta-1b. A significant positive correlation between relative affinity values and therapy duration indicates affinity maturation as another qualitative factor in IFNbeta neutralization.

Analysis of Variance↗

PubMed2006

Guidelines on routine cerebrospinal fluid analysis. Report from an EFNS task force.

A great variety of neurological diseases require investigation of cerebrospinal fluid (CSF) to prove the diagnosis or to rule out relevant differential diagnoses. The objectives were to evaluate the theoretical background and provide guidelines for clinical use in routine CSF analysis including total protein, albumin, immunoglobulins, glucose, lactate, cell count, cytological staining, and investigation of infectious CSF. The methods included a Systematic Medline search for the above-mentioned variables and review of appropriate publications by one or more of the task force members. Grading of evidence and recommendations was based on consensus by all task force members. It is recommended that CSF should be analysed immediately after collection. If storage is needed 12 ml of CSF should be partitioned into three to four sterile tubes. Albumin CSF/serum ratio (Qalb) should be preferred to total protein measurement and normal upper limits should be related to patients' age. Elevated Qalb is a non-specific finding but occurs mainly in bacterial, cryptococcal, and tuberculous meningitis, leptomingeal metastases as well as acute and chronic demyelinating polyneuropathies. Pathological decrease of the CSF/serum glucose ratio or increased lactate concentration indicates bacterial or fungal meningitis or leptomeningeal metastases. Intrathecal immunoglobulin G synthesis is best demonstrated by isoelectric focusing followed by specific staining. Cellular morphology (cytological staining) should be evaluated whenever pleocytosis is found or leptomeningeal metastases or pathological bleeding is suspected. Computed tomography-negative intrathecal bleeding should be investigated by bilirubin detection.

Advisory Committees↗

PubMed2004

Interferon-beta: the neutralizing antibody (NAb) titre predicts reversion to NAb negativity.

BACKGROUND: It has been reported that in some patients with MS who develop neutralizing antibodies (NAbs) against interferon beta (IFNbeta), antibody levels can initially increase and then decrease thereafter even when treatment is continued. OBJECTIVE: To determine whether NAb titre correlates with time to reversion to NAb negativity in patients with multiple sclerosis (MS). METHODS: Twenty-eight patients with MS who were NAb-positive during treatment with one of the currently available IFNbetas were included in this retrospective study. NAb titres were determined by the myxovirus resistance protein A induction assay. Patients were considered NAb-positive if they had at least two consecutive samples with titres of > or = 20 neutralizing units (NU). Reversion to NAb-negative status was defined as two consecutive negative samples (NAb titre of < 20 NU) after NAb positivity. RESULTS: When measured two years after treatment initiation, a NAb titre of < 75 NU had a 91.7% sensitivity and a 87.5% specificity for reversion to NAb negativity in the following two years (after a total of four years of treatment). In addition, somewhat surprisingly, patients whose serum converted to NAb-negative generally developed peak NAb titres earlier than patients who remained NAb-positive (mean time of first detection was 21 versus 38 months, respectively). CONCLUSION: The NAb titre might support treatment decisions in patients with MS whose test results are positive for NAbs.

Adjuvants, Immunologic↗

PubMed2003

A novel and rapid assay for the detection of neutralizing antibodies against interferon-beta.

There is evidence that neutralizing antibodies (NAB) have a negative influence on the clinical and magnetic resonance imaging effects of interferon-beta (IFNbeta) in multiple sclerosis (MS) patients. The current methods for NAB detection are restricted to specialized laboratories because they require a cell culture and sometimes a viral culture. Results are typically obtained after several weeks. Therefore, the development of a simple and rapid assay for the detection of NAB was sought. Whole blood samples from 28 NAB-positive patients and 110 NAB-negative patients (52 with IFNbeta and 58 without IFNbeta therapy) were incubated with IFNbeta 976 IU/mL for 24 hours. MxA protein levels--a specific marker of class I IFN bioactivity--were measured in paired samples with and without IFNbeta incubation and the difference in MxA levels was calculated. The mean increase of MxA levels after stimulation with IFNbeta in the NAB-positive group was 8 ng/mL (range 0-44 ng/mL) and in the NAB-negative group was 84 ng/mL (range 0-302 ng/mL). Using an increase of 22.5 ng/mL as cut-off) the specificity of the MxA stimulation assay was 81.2% and the sensitivity was 96.4%. The whole blood MxA stimulation assay is virtually as sensitive as the conventional NAB assay but somewhat less specific. However, this is outweighed by the procedural advantage of the assay, which is simpler, quicker and much less expensive.

Adjuvants, Immunologic↗

PubMed2002

Autonomic instability, as measured by pupillary unrest, is not associated with multiple sclerosis fatigue severity.

Multiple sclerosis (MS) fatigue is one of the most common symptoms in MS, but its pathophysiology is still not understood Sympathovagal imbalance was suggested as a reason for fatigue in chronic fatigue syndrome. We examined the role of an imbalance in the central autonomic nervous system (ANS) as a cause of MS fatigue in 51 MS patients and a control group of 22 healthy volunteers. Fatigue was assessed with the revised MS Fatigue Severity Scale (FSS) and the Modified Fatigue Impact Scale (MFIS). Depression was evaluated with the Beck Depression Inventory (BDI). Disintegration of the central ANS expressed by pupillary fatigue waves was measured with pupillography and documented in the pupillary unrest index (PUI). All subjects had less than five points on the seven-point Stanford Sleepiness Scale and were therefore not sleepy. MS patients had significant higher mean FSS scores (p=0.001) and mean MFIS scores (p=0.003) than our control group. Mean BDI scores were significant higher (p=0.001) in the MS group, but were in the lowest score range (0-10 points) in both groups. Surprisingly, we found a statistically significant inverse correlation between PUI values and either FSS scores (p=0.001; r=-0.521) or MFIS scores (p=0.002; r=-0.423) in the MS group, but not in healthy participants. We therefore conclude that autonomic instability, as measured by pupillary unrest is not associated with MS fatigue severity.

Adolescent↗

PubMed2001

Increased intrathecal production of apolipoprotein D in multiple sclerosis.

Apolipoprotein D (apoD) is a small glycoprotein responsible for the local transport of small hydrophobic ligands. Within the nervous system, apoD may be an acute phase protein that is upregulated in a variety of neuropathological conditions and is involved in the removal of lipids during nerve cell degeneration and provision of lipids during the regenerative phase. In this study, we measured cerebrospinal fluid (CSF) and serum apoD levels in patients with multiple sclerosis (MS), chronic inflammatory demyelinating polyneuropathy (CIDP), Guillain-Barré Syndrome (GBS), infectious inflammatory neurological diseases (IND) and non-inflammatory neurological diseases (NND). We found that mean CSF apoD levels are significantly increased in patients with CIDP/GBS reflecting an acute blood-nerve barrier leakage. In contrast, MS is characterized by an increased intrathecal apoD release as measured by the apoD index. Thus, the results of our study provide the first evidence of an increased intrathecal production of apoD in MS. Moreover, we demonstrate that mean apoD indices are highest in MS patients at the time of their first clinical exacerbation. CSF apoD levels and apoD indices correlate with MS disease duration but not with disability or age. Finally, we found that corticosteroid treatment resulted in significantly elevated CSF apoD levels.

Adrenal Cortex Hormones↗

PubMed2001

Anti-MOG and anti-MBP antibody subclasses in multiple sclerosis.

In a subset of multiple sclerosis (MS) patients antibodies against myelin antigens seem to be important in the demyelinating process. In this study we investigated IgM, IgA and IgG serum antibodies against the myelin oligodendrocyte glycoprotein (MOG) and the myelin basic protein (MBP) in 261 MS patients. Seventy-two per cent had anti-MOG antibodies, 59% were anti-MBP seropositive. The dominating antibody was anti-MOG IgM. A significant relationship between IgA and a progressive disease course was found. The predominance of IgGI together with the significantly associated occurrence of IgG3 against MOG corresponds to the prevailing IgGI and IgG3 isotypes in other autoimmune diseases. Patients who actually suffered from a relapse were significant more often anti-MOG and anti-MBP IgG3 seropositive than those in remission. However, patients treated either with intravenous immunoglobulins or interferon-beta showed a significant reduction of anti-MOG IgG3 antibodies.

Adult↗

PubMed1999

Antibodies against the myelin oligodendrocyte glycoprotein and the myelin basic protein in multiple sclerosis and other neurological diseases: a comparative study.

In experimental animal models of multiple sclerosis demyelinating antibody responses are directed against the myelin oligodendrocyte glycoprotein (MOG). We have investigated whether a similar antibody response is also present in multiple sclerosis patients. Using the recombinant human extracellular immunoglobulin domain of MOG (MOG-Ig) we have screened the sera and CSFs of 130 multiple sclerosis patients, 32 patients with other inflammatory neurological diseases (OIND), 30 patients with other non-inflammatory neurological diseases (ONND) and 10 patients with rheumatoid arthritis. We report that 38% of multiple sclerosis patients are seropositive for IgG antibodies to MOG-Ig compared with 28% seropositive for anti-myelin basic protein (MBP). In contrast, OIND are characterized by similar frequencies of serum IgG antibody responses to MOG-Ig (53%) and MBP (47%), whereas serum IgG responses to MOG-Ig are rare in ONND (3%) and rheumatoid arthritis (10%). Anti-MBP IgG antibodies, however, are a frequent finding in ONND (23%) and rheumatoid arthritis (60%). Our results provide clear evidence that anti-MOG-Ig antibodies are common in CNS inflammation. However, in OIND these antibody responses are transient, whereas they persist in multiple sclerosis. We demonstrate that the serum anti-MOG-Ig response is already established in early multiple sclerosis (multiple sclerosis-R0; 36%). In later multiple sclerosis stages frequencies and titres are comparable with early multiple sclerosis. In contrast, the frequency of anti-MBP antibodies is low in multiple sclerosis-R0 (12%) and increases during disease progression in relapsing-remitting (32%) and chronic progressive multiple sclerosis (40%), thus suggesting that anti-MBP responses accumulate over time. Finally we provide evidence for intrathecal synthesis of IgG antibodies to MOG-Ig in multiple sclerosis.

Adult↗

PubMedDate not supplied

Evaluations of correctional treatment programs in Germany: a review and meta-analysis.

This study presents a review and meta-analyses of research on the recidivism-reducing impact of correctionally based treatment programs in Germany. The data are part of the Correctional Drug Abuse Treatment Effectiveness (CDATE) project meta-analytic database (covering 1968-1996) of evaluation research studies of correctional interventions. Overall, the five studies of educational programs show no practical impact of these programs in reducing recidivism. Four studies of programs to counsel driving-under-the-influence (DUI) offenders fall in an intermediate area (not statistically significant, but promising enough to warrant further research). The eight studies of Social Therapy programs did show, on the average, a statistically significant practical impact in reducing recidivism.

Alcoholism↗