PubMed Health⌕ Search

Biomedical subjects

C Vedeler

Publications and source records attributed to C Vedeler.

At least 19 recordsLinked to original sources
PubMed2007

Isoelectric focusing is superior to immunofixation electrophoresis in diagnosing CNS inflammation.

BACKGROUND: A sensitive method to detect intrathecal IgG production is important in diagnosing inflammatory central nervous system (CNS) diseases, including multiple sclerosis (MS). OBJECTIVE: To compare cerebrospinal fluid (CSF) electrophoresis with isoelectric focusing (IEF), immunofixation-peroxidase electrophoresis (IFPE) and high-resolution agarose electrophoresis with protein-staining (HRAGE). METHODS: Paired serum and CSF samples from 307 consecutive patients attending a general neurology clinic were examined with IEF, IFPE and HRAGE. Clinical diagnosis was based on review of the patients' medical records after an average of 4 years. RESULTS: The sensitivity for detecting any inflammatory (autoimmune or infectious) CNS disease (52 patients) was 67% for IEF, 50% for IFPE and 29% for HRAGE. The sensitivity for detecting MS (14 patients) was 93%, 86% and 29% respectively. The sensitivity for detecting clinically isolated syndrome (eight patients) was 75%, 25% and 13% respectively. The number of oligoclonal bands in IEF was higher in inflammatory than in non-inflammatory neurological diseases or symptoms, but similar in MS and other inflammatory diseases. CONCLUSION: IEF is the method of choice in diagnosing intrathecal IgG synthesis.

Adolescent↗
PubMed2006

Multiplexed phosphoprotein analysis in immune cells.

Analyzing signaling networks in immune cells is of particular interests in diseases where treatment choices are preferentially immunomodulatory. By combining phospho-specific antibodies with multicolor flow cytometry it is possible to perform quantitative multiparameter analysis of signaling pathways within complex cell populations. Multiplexed phosphoprotein analysis will potentially incorporate environmental factors such as toxins or pathogens and genetic variability of individual patients in a step towards personalized medicine.

Humans↗
PubMed2006

Proteomic-based biomarker discovery with emphasis on cerebrospinal fluid and multiple sclerosis.

Discovery of disease specific biomarkers in human body fluids has become an important challenge in clinical proteomics. Facing the increasing threat of degenerative and disabling diseases like cancer, cardiovascular, neurological and inflammatory diseases in large parts of the world's population, there is an urgent need to improve early diagnostics. In this review we discuss possibilities and limitations connected to using mass spectrometry based proteomics in the search for novel biomarkers, with focus on multiple sclerosis as a typical representative for the large group of non-curable degenerative and disabling disease with the lack of specific tests for early diagnosis. Careful control of the pre-analytical phase including sampling, storage and fractionation of samples, in addition to a thoroughly considered patient selection, is important in order to avoid false biomarkers to appear in the resulting mass spectra. Furthermore, advanced computational tools are needed in order to discover potential biomarkers from the enormous data amounts generated by the mass spectrometers. The development of such computer tools is a research field currently in the start phase and could prove to be a bottle neck in the biomarker discovery the next years. Therefore, a rather detailed review of the most used computational and pre-analytical methods is given in this review. Mass spectrometry based biomarker discovery is undoubtedly still in its early infancy. However, in light of the potential of this technology to provide deep coverage of the body fluid proteomes, it will certainly consolidate its role in developing molecular medicine into clinical practice.

Biomarkers↗
PubMed2005

Onset and course of chronic inflammatory demyelinating polyneuropathy.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is clinically heterogeneous. Our purpose was to determine whether initial progression time, clinical features, and distribution of nerve conduction slowing at presentation correlate with clinical course and prognosis. We examined how findings at presentation related to clinical course during an average follow-up time of 4.0 (range 1.0-9.0) years in 44 patients with CIDP. We calculated terminal latency index (TLI), a measure of differential slowing in distal relative to more proximal nerve segments. Patients with acute or subacute onset (progression over less than 8 weeks) had a higher remission rate (P = 0.012) than patients with chronic onset (progression over more than 8 weeks). Patients with proximal weakness had a higher remission rate than patients with the distal phenotype (P < 0.001). All 5 patients with a relapsing course had subacute onset. They had lower TLIs, suggesting a more distal pattern of demyelination, than patients with a monophasic or chronic course. In conclusion, subacute onset and presence of proximal weakness are good prognostic signs that correlate with a high rate of recovery to normal in CIDP. Distal accentuation of conduction slowing at presentation correlates with subacute onset and a relapsing course.

Acute Disease↗
PubMed2004

The effects of interferon-alpha2a on concentrations of immunoglobulins, complement and lymphocytes in patients with multiple sclerosis.

Multiple sclerosis (MS) patients treated with type I interferon experience reduced disease activity. Because immunoglobulins (Igs), complement and lymphocytes have been given a role in the pathogenesis of MS, we investigated the longitudinal effect of interferon-alpha2a (IFNA) on the variability of these parameters. Patients were treated for 6 months with 4.5 million international units (MIU) IFNA (24 patients), 9.0 MIU IFNA (21 patients) or placebo (23 patients). IFNA induced a significant increase in concentrations of total IgG and IgG subclasses 1, 3 and 4. At 6 months, the mean concentration of IgG had increased by 1.51 g/l (CI: 0.82, 2.21) in the 9.0 MIU IFNA group. There was no significant effect of IFNA treatment on concentrations of IgG2 and IgA, while the effect on IgM was borderline significant. After 6 months, IgM had increased by 0.29 g/l (CI: -0.01, 0.65) in the 9.0 MIU IFNA group. IFNA induced a significant increase in the concentration of C1 inhibitor (INH). At 3 months, the mean concentration of C1 INH had increased by 0.033 g/l (CI: 0.01, 0.05). At 3 months, C4 had increased by 0.05 g/l (CI: 0.01, 0.09) in the 9.0 MIU IFNA group. The effect of IFNA on C4 was inconclusive but indicates an effect during the initial phase of the treatment. C3 showed no significant treatment-mediated change. IFNA induced a significant decrease in lymphocyte concentrations by 0.56 x 106 lymphocytes/ml (CI: -0.81, -0.31) at 3 months. There were no significant associations between changes in immune parameters and changes in clinical and magnetic resonance imaging scores. The results verify that IFNA modulates and activates both the innate and the adaptive arms of the immune system. The observations should be of relevance when evaluating mechanisms of action of IFN treatment in MS.

Antineoplastic Agents↗
PubMed2003

FcgammaRIIa and FcgammaRIIIb polymorphisms were not associated with meningococcal disease in Western Norway.

Fcgamma-receptor (FcyR) polymorphisms have been associated with acquisition and severity of invasive meningococcal disease. We studied FcgammaR polymorphisms in a population with a high incidence of meningococcal disease. Fifty meningococcal disease patients aged 14-60 years, with bacteriologically confirmed disease and without detected complement deficiency, together with 100 healthy adult controls were included in the study. Clinical and bacteriological data were collected prior to FcgammaRIIa and FcgammaRIIb genotyping, which was performed by polymerase chain reaction. The distribution of the FcgammaRIIa and FcgammaRIIIb allotypes and their allele frequencies were not significantly different amongst the patients and the controls. The combination FcgammaRIIa-R/R and FcgammaRIIb-Na2/Na2 was less common among patients than controls (OR = 0.11, Fisher's exact P = 0.05). No significant association was found between the two FcgammaRs and severity of disease, meningococcal serogroup, age groups or gender. In contrast to previous findings, our study indicates that in Norwegian teenagers and adults, the FcgammaRIIa and FcgammaRIIIb allotypes are not decisive for the acquisition or for the severity of meningococcal disease.

Adolescent↗
PubMed2003

Autoantibodies against complement receptor 1 (CD35) in SLE, liver cirrhosis and HIV-infected patients.

The acquired loss of CR1 (CD35) on erythrocytes in specific autoimmune diseases and chronic infections may be due to autoAb against CR1. An ELISA using rCR1 was established to measure antiCR1 IgG autoAb. Plasma containing alloAb to polymorphism on CR1 (Knops blood group Ab) reacted strongly against rCR1 and were used as positive controls. AntiCR1 Ab was found in 3/90 (3.5%) plasma samples from healthy blood donors. The binding of these Ab was not inhibited by high salt concentrations. AntiCR1 Ab were present in the IgG fractions of plasma, and they bound to rCR1 on Western Blot. Affinity chromatography on rCR1-sepharose depleted the plasma of antiCR1, and the acid-eluted fractions contained the antiCR1 Ab. An increased frequency of antiCR1 autoAb was found in patients with SLE (36/78; 46%), liver cirrhosis (15/41; 36%), HIV infection (23/76; 30%) (all P < 0.0001), and in patients with anticardiolipin Ab (4/21; 19%, P < 0.01) multiple sclerosis (7/50; 14%, P < 0.02), and myeloma (autoAb (8/56; 14%, P < 0.02), but not in those with acute poststreptococcal glomerulonephritis (1:32; 3%). Because C1q binds to CR1, antiC1q Ab were analysed in the same patients. There was no correlation between levels of antiC1q and antiCR1 autoAb. In HIV patients, levels of antiCR1 did not correlate with low CR1 levels expressed on erythrocytes or soluble CR1 in plasma. The binding of antiCR1 autoAb to rCR1 fixed on ELISA plates was not inhibited by soluble rCR1 or by human erythrocyte CR1, in contrast to alloAb and one SLE serum, which induced partial blockade. Thus, antiCR1 autoAb recognize mostly CR1 epitope(s) not present on the native molecule, suggesting that they are not directly involved in the loss of CR1. Rather antiCR1 autoAb might indicate a specific immune response to denatured CR1.

Autoantibodies↗
PubMed2001

[Hereditary neuropathy with pressure palsies].

BACKGROUND: Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant polyneuropathy usually caused by a deletion in the gene coding for the peripheral nerve myelin protein 22 (PMP22). The patients usually get relapsing and remitting focal nerve symptoms due to mechanical factors like pressure or minor trauma that normal nerves tolerate. MATERIAL AND METHODS: Two patients from different families have been examined clinically, neurophysiologically and genetically by Southern blot and PCR techniques. RESULTS: The clinical and neurophysiological findings were typical of this disorder, and the DNA tests showed deletions in the PMP22 gene. INTERPRETATION: We discuss clinical, neurophysiological and molecular diagnostics, pathomechanisms, treatment and secondary prevention. Early diagnosis may be important for optimal management of the patients.

Adult↗
PubMed2001

[Peripheral neuropathy in cancer].

Neuropathy is a quite common finding in cancer patients. If the cancer is known, the main clinical problem is often whether the symptoms and signs are caused by metastasis or recurrence, or if the neuropathy can be related to effects of the oncological treatment. In addition to the clinical findings, radiological and neurophysiological examination can often be of considerable diagnostic help. Peripheral neuropathy may also be the first manifestation of the cancer, as in paraneoplastic neuropathies. Detecting the tumor in these cases may improve the oncological prognosis, as the neuropathy often precedes tumor symptoms by several years. A determined approach in searching for an occult cancer is necessary. The neuropathic symptoms are seldom life-threatening. However, the neuropathy may cause distressing symptoms, and symptomatic treatment and rehabilitation is often required.

Antineoplastic Agents↗
PubMed2001

Neuropathy and malignancy: a retrospective survey.

Peripheral neuropathy is a common condition with a variety of causes. In some cases the neuropathy is the first symptom of an underlying malignancy. The frequency of occult cancer in patients with neuropathy is of importance in planning the investigations and follow-up of these patients. This retrospective study examined the incidence of cancer-related neuropathy among patients originally diagnosed with idiopathic peripheral neuropathy. Between 1981-1995 our department discharged 187 patients with the diagnosis of idiopathic peripheral neuropathy. Their names were cross-matched with the Norwegian Cancer Registry, and the medical records of the patients with known cancer were reviewed. In 14 patients (7.5%) we found cancer as the probable cause of the peripheral neuropathy originally classified as idiopathic. In eight of the patients the neuropathic symptoms preceded the tumour. In six cancer was already diagnosed when the neuropathic symptoms developed, but in three of these the neuropathy heralded a tumour recurrence. Idiopathic progressive neuropathy should always raise the suspicion of an underlying malignancy, especially if there are atypical accompanying symptoms and signs.

Adult↗
PubMed2001

Complications after LP related to needle type: pencil-point versus Quincke.

OBJECTIVES: We studied the incidence of complications after diagnostic lumbar puncture (LP) related to needle type. MATERIAL AND METHODS: A 5 months' observational study of routine diagnostic LP in 83 patients was conducted. RESULTS: Significantly more headache was observed after LP using thicker cutting needles (20G Quincke) compared with thinner cutting or non-cutting needles (22G Quincke or pencil-point). No significant difference in complications after LP was found between the 22G Quincke and pencil-point needles. CONCLUSION: The size of the needle and not the needle shape seems to be the main determinant for post-dural puncture headache (PDPH).

Adult↗
PubMed2001

Disability and prognosis in multiple sclerosis: demographic and clinical variables important for the ability to walk and awarding of disability pension.

OBJECTIVE: To evaluate disability and prognosis in an untreated population-based incidence cohort of multiple sclerosis (MS) patients. METHODS: The Expanded Disability Status Scale (EDSS) score was recorded in 220 MS patients. Disease progression was assessed by life table analysis with different endpoints and multivariate Cox regression analysis was performed for evaluation of prognostic factors. RESULTS: The probability of being alive after 15 years was 94.8 +/- 1.8% (s.e.), of managing without a wheelchair (EDSS < 7.0) 75.8 +/- 3.2%, of walking without walking assistance (EDSS<6.0) 60.3 +/- 3.6%, and of not being awarded a disability pension 46.0 +/- 3.7%. The probability of still having a relapsing-remitting (RR) course after 15 years was 62.0 +/- 4.1%. A RR course and long interval between the initial (onset) and second episode (> 3 years) predicted favorable outcome. There was also a trend towards favorable outcome in patients with optic neuritis, sensory symptoms and low age at onset but these factors were associated with the RR course. Motor symptoms and high age at onset indicated unfavorable outcome, but these factors were associated with the primary progressive course. CONCLUSIONS: A RR course and long inter-episode intervals in the early phase of the disease were associated with a better outcome. Other onset characteristics indicating a favorable outcome were associated with the RR course while characteristics indicating an unfavorable outcome were associated with the PP course.

Adult↗
PubMed2000

Complement activation by titin and ryanodine receptor autoantibodies in myasthenia gravis. A study of IgG subclasses and clinical correlations.

To elucidate the mechanism of immune damage caused by titin and ryanodine receptor (RyR) autoantibodies in myasthenia gravis (MG), we studied the complement-activating capacity and the IgG subclass distribution of these autoantibodies in sera from 49 MG patients. Complement activation occurred in 38 out of 49 titin antibody positive sera, and in 14 out of 21 RyR antibody positive sera. The titin antibodies occurred only in the IgG 1 and IgG 4 subclasses, whereas the RyR antibodies occurred in all four IgG subclasses but with IgG 1 predominance. Complement-activating RyR antibodies occurred with higher frequency in sera of thymoma MG than of late-onset MG. RyR IgG 1 antibodies occurred more often in severe MG than in mild and moderate disease groups. Mean total IgG and IgG 1 titin and RyR antibody titers fell during long-time patient observation together with an improvement of the MG symptoms.

Adult↗
PubMed2000

[Polyneuropathy is an early finding in primary systemic amyloidosis].

BACKGROUND: Polyneuropathy is associated with several pathological conditions. Amyloidosis is a less common cause of polyneuropathy. Amyloidosis is caused by the accumulation of insoluble protein fibrils (amyloid) in the extracellular matrix. Primary systemic amyloidosis is caused by B-lymphocyte dyscrasia. Polyneuropathy is the first sign of primary systemic amyloidosis in about 20% of the cases, and is characterised by relentless progression, painfulness, and prominent symptoms of autonomic neuropathy. MATERIAL AND METHODS: We describe three cases of primary systemic amyloidosis that started with polyneuropathy. RESULTS: The diagnosis of primary systemic amyloidosis is often delayed more than two years after the onset of polyneuropathy. Biopsy of rectum, fat tissue, bone marrow, or peripheral nerve are diagnostic tools. INTERPRETATION: The survival of non-treated patients is about 18 months after the diagnosis. With chemotherapy the survival is prolonged to approximately 38 months.

Aged↗
PubMed2000

[Neurological diseases associated with celiac disease].

During the period from May 1997 to October 1998, eight patients with coeliac disease or dermatitis herpetiformis and neurological disorders were admitted to the Department of Neurology, University Hospital of Bergen. The most frequent conditions were polyneuropathy (seven patients) and spinocerebellar ataxia (three patients). Other conditions were lower motor neuron disease, myelopathy, epilepsy and encephalopathy. The patients used various degrees of gluten-free diet at the time of admission. It remains unclear whether there is a shared common pathogenetic mechanism or the neurological disorder is a complication to the coeliac disease. Both vitamin depletion and immunological mechanisms may cause neurological disorder. Neurological manifestations may occur before the gastrointestinal symptoms. With reference to our patients and available literature we discuss prevalence, clinical picture, pathogenesis, treatment and prognosis. Neurologists, gastroenterologists and general practitioners should be aware that coeliac disease can cause neurological diseases, especially polyneuropathy, cerebellar ataxia and encephalopathy.

Adult↗
PubMed2000

EFNS task force report: a questionnaire-based survey on the service provision and quality assurance for determination of diagnostic autoantibody tests in European neuroimmunology centres. European Federation of Neurological Societies.

Autoantibodies to a wide variety of neural components are frequently sought in the sera of patients with neurological diseases suspected to have an antibody-associated autoimmune basis. Variations in assay methodology and availability are likely to exist throughout European diagnostic immunology centres, and interlaboratory discrepancies in performance for some assays have been reported. The availability of quality assurance is largely unknown. In this questionnaire-based EFNS task force, all 18 national representatives of the Neuroimmunology Panel within the EFNS were invited to estimate the service provision within their country; 12 panel members responded. From these responses, it emerged that a range of assays are being performed throughout European centres, involving over 20 separate antigens, using a broad array of immunodetection techniques. With the exception of the estimation of anti-AChR antibodies for the diagnosis of myasthenia gravis, no systematic quality assurance schemes are available, this being conducted on an ad hoc basis, or not at all. Since quality is a central component of assay sensitivity and specificity, we conclude that there is an urgent need to introduce pan-European quality assurance schemes, based on provision of positive and negative test sera from a central source, and in which all neuroimmunology laboratories should participate.

Autoantibodies↗
PubMed1999

Immunoglobulin G Fc-receptor (FcgammaR) IIA and IIIB polymorphisms related to disability in MS.

OBJECTIVE: MS is immunologically mediated in genetically susceptible individuals. Receptors for the Fc fragment of immunoglobulin G (IgG) (FcgammaR) link the humoral and cellular immune responses by targeting immune complexes to effector cells. Different FcgammaR show variability in their distribution, strength, and capacity of binding different IgG subclasses. METHODS: To investigate the role of FcgammaR in MS, 136 MS patients and 96 matched controls were genotyped for FcgammaRIIA and FcgammaRIIIB gene polymorphisms; the results were correlated to disease susceptibility and severity measured by the Expanded Disability Status Scale (EDSS). RESULTS: The allele frequencies of the FcgammaRIIA and FcgammaRIIIB did not differ significantly between the MS patients and the controls. Patients homozygous for the FcgammaRIIIB neutrophil antigen (NA) 1 allele had a significantly more benign course of MS than patients heterozygous or homozygous for the FcgammaRIIIB NA2 allele. Patients homozygous for the FcgammaRIIA histidine (H) allele also had a more benign course of MS than patients heterozygous or homozygous for the FcgammaRIIA arginine (R) allele. CONCLUSION: The results implicate FcgammaRIIIB and to a lesser extent FcgammaRIIA as disease-modifying genes in MS. FcgammaRIIIB NA1/NA1 and FcgammaRIIA H/H bind more efficient IgG1/IgG3 and IgG2 subclasses, respectively, than FcgammaRIIIB NA2/NA2 and FcgammaRIIA R/R. A more effective processing of circulating immune complexes may be one mechanism for better clinical outcome in MS.

Adolescent↗