A W Teelken

University of Groningen, Groningen, Province of Groningen, Netherlands

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Publications (57)338.41 Total impact

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    ABSTRACT: The reason for increased peripheral blood leukocyte (PBL) nitric oxide (NO) production in patients with multiple sclerosis (MS) is unknown. To investigate whether PBL NO production is related to measures of oxidative stress. PBL nitrite, diene conjugates (DC, a measure of undergone oxidative stress), antiradical activity (ARA) and antioxidant acitvity (AOA) were measured in 35 healthy control persons and 80 patients with MS. We investigated the correlation of these measures with a partial correlation analysis, with age as the control variable. There was a significant correlation in both MS patients and healthy control persons between PBL nitrite levels and PBL DC, ARA and AOA. The correlations were stronger in healthy control persons. An analysis by disease subtype showed that the correlations were present in patients with relapsing-remitting and secondary progressive MS, but absent in primary progressive MS. PBL nitrite levels and measures of oxidative stress are closely related in MS-patients as well as in healthy control persons. Increased serum NO levels in MS may be the result of a physiologic reaction to overall oxidative stress. The differences in the strength of correlation between different disease subtypes may reflect differences in leukocyte biology.
    Multiple Sclerosis 04/2008; 14(2):159-65. · 4.47 Impact Factor
  • European Journal of Neurology 01/2008; 15(4). · 4.16 Impact Factor
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    ABSTRACT: Antibody-mediated inflammation is believed to contribute to tissue injury in multiple sclerosis (MS). The majority of patients with MS have oligoclonal bands (OCB), corresponding to antibodies against a variety of antigens, in their cerebrospinal fluid (CSF). The relation of CSF OCB and disease progression in MS is uncertain. To investigate whether there is a relation between CSF OCB and a more aggressive disease course of MS, 143 patients with definite MS according to the Poser diagnostic criteria and CSF analysis at time of diagnosis were followed over a period of 5 years. There were no differences in presence or number of CSF OCB between patients with significant worsening of disability and stable patients. There were no differences in presence or number of CSF OCB between patients with stable relapsing-remitting MS and patients developing secondary progression during follow-up. The presence or number of CSF OCB does not seem to influence early disease progression in MS.
    European Journal of Neurology 08/2007; 14(7):797-800. · 4.16 Impact Factor
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    ABSTRACT: Oxidative stress has been implicated in the pathophysiology of multiple sclerosis (MS), but its relation to disease progression is uncertain. To evaluate the relationship of plasma lipid peroxidation with progression of disability in MS, we measured blood plasma fluorescent lipid peroxidation products (PFLPP) levels in 23 patients with RRMS with a benign course, 32 with secondary progressive MS, 24 with primary progressive MS and 30 healthy controls. None of the patients had a relapse within the previous 3 months. Progression of disability was evaluated during a follow-up period of 5 years by the Expanded Disability Status Scale (EDSS) and the Multiple Sclerosis Severity Score (MSSS). We found plasma PFLPP levels elevated in patients with MS compared with controls (P < 0.0001), but there was no difference between patients with a benign and progressive disease course. There was no correlation between PFLPP levels and worsening of disability on the EDSS and speed of progression on the MSSS. Our data suggest that there is no relation between the degree of oxidative stress in plasma and progression of disability in MS.
    European Journal of Neurology 05/2007; 14(5):529-33. · 4.16 Impact Factor
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    ABSTRACT: Plasma levels of the glial cell marker S100beta and the neuronal marker neuron-specific enolase (NSE) are elevated in various conditions of central nervous system damage. In this study we investigated whether plasma levels of S100beta and NSE are related to disease progression in multiple sclerosis (MS). Plasma levels of S100beta and NSE were measured in 25 patients with relapsing remitting MS (RRMS), 23 with secondary progressive MS (SPMS) and 16 with primary progressive MS (PPMS). All MS patients were in a clinically stable phase. Progression and disability were evaluated during a follow-up period of five years. We found that plasma NSE levels were lower in patients with clinically relevant worsening on the Expanded Disability Status Scale (EDSS), defined as 1 point increase from EDSS <6.0 or 0.5 point increase from EDSS> or =6 after five years (p=0.042), and in patients with a progressive disease course (p=0.01). There was a significant negative correlation between plasma NSE levels and both EDSS and Multiple Sclerosis Severity Status (MSSS) scores at baseline and after five years of follow-up (r=-0.33 and -0.38, p=0.027 and 0.003). There were no significant differences between patient groups in plasma S100beta levels. Plasma NSE levels appear inversely related to disease progression in MS.
    Journal of the Neurological Sciences 01/2007; 252(2):154-8. · 2.24 Impact Factor
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    ABSTRACT: The pathophysiology involved in human neonatal high-pressure hydrocephalus (HC) includes both cerebrospinal fluid (CSF) malabsorption and obstruction. The aim was to estimate the relative contribution between CSF malabsorption and obstruction in three different etiological groups of neonatal high-pressure HC by assessment of specific CSF biomarkers indicative of growth factor- and fibrosis-related CSF malabsorption (transforming growth factor beta-1 (TGF beta-1), aminoterminal propeptide of type 1 collagen (PC1NP)]. Patients were subdivided into three groups. Group A: spina bifida HC (n=12); group B: non-haemorrhagic triventricular HC (n=4); and group C: posthaemorrhagic HC (n=6). To exclude for confounding differences in pro-inflammatory state between the three groups, interleukin-6 (IL-6) CSF concentrations were assessed. Consecutively, the CSF concentrations of TGF beta-1 and PC1NP were compared between the different groups. Median CSF concentrations of IL-6 were low and did not differ between groups. Median CSF concentrations of PC1NP were significantly lower in group A (median: 180 ng/ml, range 90-808) than in group C (median: 1,060, range 396-1194; p=0.002). TGF beta-1 concentrations were significantly higher in group C (median 355 pg/ml, range 129-843) than in groups A (median 103, range 78-675 pg/ml) and B (median 120 pg/ml, range 91-188; p=0.01 and 0.03, respectively). In neonatal posthaemorrhagic HC, high concentrations of malabsorption-related biomarkers contrast with lower concentrations in SB and non-haemorrhagic triventricular HC. During the early development of high pressure HC in SB neonates, CSF biomarkers strongly indicate that CSF obstruction contributes more to the development of HC than malabsorption.
    Child s Nervous System 11/2006; 22(10):1249-55. · 1.24 Impact Factor
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    ABSTRACT: The role of oxidative stress in patients with multiple sclerosis (MS) is poorly understood. To investigate oxidative stress in serum and peripheral blood leukocytes in patients with different disease courses of MS. Diene conjugate (DC) levels (a measure of lipid peroxidation), total antioxidative activity (AOA) and total antiradical activity (ARA) were measured in serum and peripheral blood leukocytes from 30 patients with benign relapsing remitting MS (BMS), 27 with secondary progressive MS (SPMS), 29 with primary progressive MS (PPMS), and 30 healthy controls. All MS patients were in a clinically stable phase. Serum DC levels were elevated in patients with BMS (p <0.05), SPMS (p <0.01) and PPMS (p <0.001). Serum total AOA and ARA were not different between MS patients and controls. Compared to controls, leukocyte DC levels were not different in each MS subgroup, but total ARA was elevated. There was a strong correlation, both in controls and MS patients, between leukocyte DC levels and leukocyte total ARA (p <0.0001) and leukocyte total AOA (p <0.0001). Oxidative stress occurs in progressive as well as benign MS. The finding that cells withstand oxidative stress, due to upregulated cellular antioxidant defence mechanisms, suggests that reactive oxygen species (ROS) formation in MS is not necessarily deleterious.
    Journal of Neurology 05/2006; 253(4):483-7. · 3.58 Impact Factor
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    ABSTRACT: There is evidence that homocysteine contributes to various neurodegenerative disorders, and elevated plasma homocysteine levels have been observed in patients with multiple sclerosis (MS). To investigate if and why plasma homocysteine levels are increased in MS, and whether they play a role in the disease course. We compared plasma levels of homocysteine in 88 patients with MS and 57 healthy controls. In the MS group, 28 had a benign course, 37 were secondary progressive, and 23 primary progressive. To explore the underlying mechanisms, we measured serum levels of vitamins B6 and B12, folate, interleukin (IL)-12, tumour necrosis factor (TNF)-alpha, leukocyte nitric oxide production, and plasma diene conjugate levels (measure of oxidative stress). Mean (SD) plasma homocysteine concentration was higher in patients (13.8 (4.9) micromol/l) than in controls (10.1 (2.5) micromol/l; p<0.0001). However, there were no significant differences in homocysteine levels between the three clinical subgroups of MS. Serum concentrations of vitamin B6, vitamin B12, and folate were not different between patients with MS and controls. In the MS group, there were no correlations between plasma homocysteine levels and the serum concentrations of IL-12 or TNF-alpha, leukocyte nitric oxide production, or plasma diene conjugate levels. Elevated plasma homocysteine occurs in both benign and progressive disease courses of MS, and seems unrelated to immune activation, oxidative stress, or a deficiency in vitamin B6, vitamin B12, or folate.
    Journal of Neurology Neurosurgery & Psychiatry 03/2006; 77(2):189-92. · 4.92 Impact Factor
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    ABSTRACT: Background: The pathogenesis of hydrocephalus in human neonates with spina bifida aperta (SBA) is incompletely understood. Cerebrospinal fluid (CSF) outflow obstruction or arachnoideal resorption deficit may play an important role in the development of ventriculomegaly. In animal model, overexpression of transforming growth factor beta 1 (TGF beta 1) or increased local collagen turnover in the CSF lead to tissue proliferation and CSF malabsorption.
    Pediatric Research 08/2005; 58(2). · 2.67 Impact Factor
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    Cerebrospinal Fluid Research 01/2005; · 1.81 Impact Factor
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    ABSTRACT: Nitric oxide (NO) may play a role in tissue destruction and axonal degeneration in multiple sclerosis (MS). To investigate NO production by peripheral blood leukocytes (PBL) in patients with a benign and progressive course of MS. PBL were isolated from 25 patients with a benign course of MS (BMS), 33 with secondary progressive MS (SPMS), 21 with primary progressive MS (PPMS), and 29 healthy individuals. Leukocyte supernatants were assayed for nitrite concentration, which is an index of NO generation, using the Griess reaction. Serum levels of tumor necrosis factor (TNF)alpha and interleukin (IL)-12 were measured using ELISA. Compared to healthy controls, nitrite concentrations were higher in patients with BMS (p < 0.001), SPMS (p < 0.001), and PPMS (p < 0.05). There were no significant differences among the three clinical subgroups of MS. There was a correlation between nitrite concentrations and serum levels of IL-12 (p = 0.04), but not of TNFalpha. Increased NO production by PBL in patients with MS is independent of the disease course.
    Neurology 01/2004; 62(2):239-42. · 8.30 Impact Factor
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    ABSTRACT: Conventional ways of monitoring reperfusion in acute ischemic stroke have several limitations. In searching for an alternative, we evaluated biochemical serum markers of stroke change in relation to reperfusion. N-acetylaspartate (NAA) is a small amino acid synthesized by neuronal mitochondria, which can be released in the extracellular space after reperfusion in animal models of brain ischemia. S100B is a well-known peripheral marker of brain damage in various neurologic diseases, including stroke. Serum samples were analyzed from 13 patients with ischemic stroke who were either treated conservatively or with recombinant tissue plasminogen activator. Blood was drawn at baseline; after 30 minutes; after 1, 2, 4, and 8 hours; and between 12 to 24 hours. Serum concentrations of NAA were analyzed using a gas chromatography-mass spectrometry method. S100B was analyzed using an automated immunoluminometric assay. Reperfusion was assessed using transcranial Doppler and clinical criteria. Reperfusion (n = 4) was associated with a transient rapid increase in serum NAA levels. Such an early rapid increase of NAA was not observed for patients with persistent occlusion at 12 to 24 hours (n = 4) and patients with no occlusion on baseline transcranial Doppler (n = 5). NAA peak levels and area under the curve values were significantly higher after reperfusion in comparison with normal transcranial Doppler findings or persistent occlusion (P = .003 and P = .05, respectively). No differences were found between these groups for S100B levels. In patients with acute ischemic stroke, serum NAA levels transiently raise after reperfusion.
    Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association 01/2004; 13(6):254-8.
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    ABSTRACT: The gene for myeloperoxidase (MPO) has been implicated in multiple sclerosis (MS). By measuring H(2)O(2) dependent oxidation of 3,3'5,5'-tetramethylbenzidine with spectrophotometry the authors investigated MPO activity in peripheral blood leucocytes from 42 patients with MS (12 with secondary progressive MS, 17 with primary progressive MS, and 13 with relapsing remitting benign MS) and 32 healthy controls. Leucocyte MPO activity was significantly lower in patients with benign MS (mean (SEM) 0.086 (0.029) U/mg protein; p<0.01), secondary progressive MS (0.038 (0.009) U/mg protein; p<0.001), and primary progressive MS (0.057 (0.016) U/mg protein; p<0.001) compared with healthy controls (0.322 (0.053) U/mg protein). These data suggest that low MPO, which may be genetically determined, plays a part in MS pathogenesis.
    Journal of Neurology Neurosurgery & Psychiatry 07/2003; 74(7):953-5. · 4.92 Impact Factor
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    ABSTRACT: S-100B and neuron-specific enolase (NSE) serum concentrations can be used as peripheral markers of glial cell and neuronal damage, respectively. We investigated these markers in a clinical trial with the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) antagonist ZK200775 in acute ischemic stroke patients. In a multicenter, double-blind, randomized, placebo-controlled phase 2 trial, 61 ischemic stroke patients were treated with either placebo or active drug in a dose-finding design. Twenty-five patients received placebo, 12 patients received a total dose of 262.5 mg in 48 hours (dose group 1), and 13 patients received a total dose of 525 mg in 48 hours (dose group 2). Eleven patients received a total dose of 105 mg over a period of 6 hours (dose group 3; reduction of total dose and infusion time because of adverse events in group 2). Serum concentrations of S-100B and NSE were analyzed with the use of a monoclonal sandwich immunoluminometric assay. Neurological outcome was assessed with the National Institutes of Health Stroke Scale (NIHSS). In group 2 there was a significant transient worsening in the mean NIHSS score 48 hours after the start of treatment. The mean increase was 11 points. This was due to reduction of consciousness (stupor and coma) in 8 of 13 patients. Neurological deterioration in group 2 was associated with a higher increase of S-100B concentrations, but not of NSE concentrations, than in the placebo group. The trial was stopped prematurely for safety reasons. The AMPA antagonist ZK200775 transiently worsened the neurological condition in patients with acute ischemic stroke. Our results suggest that in addition to neuronal dysfunction, glial cell toxicity may have occurred. It may be useful to introduce monitoring of serum markers of brain damage in phase 2 trials with glutamate receptor antagonists.
    Stroke 01/2003; 33(12):2813-8. · 6.16 Impact Factor
  • Artificial Organs 10/2002; 26(9):815-6; author reply 816. · 1.96 Impact Factor
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    ABSTRACT: Ten heat-sensitive patients with MS were randomly allocated in a cross-over study to wear a cooling garment for 60 minutes at 7 degrees C (active cooling) and 26 degrees C (sham cooling). In contrast to sham cooling, active cooling improved fatigue and postural stability with eyes closed and muscle strength. There was no decrease in tympanic temperature, but active cooling was associated with a 41% decrease in mean leukocyte nitric oxide (NO) production (p = 0.004). This effect on NO could be relevant because it blocks conduction in demyelinated axons.
    Neurology 10/2001; 57(5):892-4. · 8.30 Impact Factor
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    ABSTRACT: Temporal changes in serum S-100 protein levels were compared between patients with ischemic stroke, transient ischemic attack (TIA) and traumatic brain injury (TBI). In addition, S-100 levels were correlated with clinical severity and outcome. Measurements were done with a LIA-mat((R)) Sangtec((R)) 100 using an automated immunoluminometric assay. Serum S-100 was measured in 21 stroke patients, 18 TIA patients and ten TBI patients on days 1 (0-24 h), 2, 3, 4, 5 or 6 and 8 or 9. In a control group of 28 healthy volunteers one measurement was done. For the stroke and TIA patients, National Institutes of Health Stroke Scale (NIHSS) scores were obtained on admission and on day 10. For the TBI patients, Glasgow Coma Scale (GCS) scores were obtained on admission and Glasgow Outcome Scale (GOS) scores were obtained after 6 months. Changes in serum S-100 levels over the first 3 days were significantly different between stroke and TBI patients (P=0.014) and between stroke and TIA patients (P=0.006). Peak concentrations of S-100 were most often observed on day 3 or 4 after stroke and on day 1 or 2 after TBI. In the stroke patients individual S-100 peak levels correlated well with the NIHSS score on admission (r=0.58 P=0.014) and the change in NIHSS score between day 10 and day 1 (r=0.65, P=0. 005). In the TBI patients a good correlation between individual peak levels of S-100 and the GCS score on admission (r=-0.81, P=0.010) and the GOS score 6 months after the trauma was found (r=-0.87, P=0. 004). We conclude that there is a significant difference in temporal changes of S-100 levels between ischemic stroke and TBI patients. This suggests different pathophysiological mechanisms. The results of this study further confirm that peak levels of serum S-100 correlate with neurological deficit resulting from either stroke or TBI.
    Journal of the Neurological Sciences 01/2001; 181(1-2):104-10. · 2.24 Impact Factor
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    ABSTRACT: Insulin-like growth factor (IGF) II receptors were studied in human adult brain by using autoradiography with [125I]IGF-II. Receptors were found to be widely distributed throughout all neuronal regions. The highest densities were found in plexus choroideus, granular layer of the cerebellar cortex, gyrus dendatus and pyramidal layer of the hippocampus, striatum, and cerebral cortex. White matter was devoid of IGF-II receptors. We also examined [125I]IGF-II binding in six plaques of multiple sclerosis, which were characterized by a dense network of astrocytes. We were unable to detect IGF-II receptors in any of the astrogliotic plaques, suggesting that IGF-II receptors in human brain are not involved in astrogliosis. The regional variations in neuronal distribution of IGF-II receptors suggest involvement of IGF-II in functions associated with specific neuronal pathways.
    Brain Research 05/2000; 863(1-2):282-8. · 2.88 Impact Factor
  • J De Keyser, M Schaaf, A Teelken
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    ABSTRACT: The myelin sheath in multiple sclerosis (MS) appears to contain a higher proportion of the citrullinated isoform of myelin basic protein MBP-C8. In vitro, MBP-associated arginine is deiminated to citrulline by the enzyme peptidylarginine deiminase (PAD). We investigated PAD activity in white matter from postmortem human brain samples by measuring the formation of citrulline from benzoylarginine ethyl esther. PAD activity in MS white matter was not different from that in controls. In neonates, in whom MBP is exclusively of the C8 type, white matter PAD activity was not different from that in adults. Our results suggest that in human brain either PAD plays no role in the formation of MBP-C8, or there may be a better accessibility of MBP in myelin in neonates and MS to the enzyme.
    Neuroscience Letters 02/1999; 260(1):74-6. · 2.03 Impact Factor
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    ABSTRACT: The insulin-like growth factor (IGF) system influences oligodendrocyte survival, myelination, and immune functions. We examined whether alterations in the circulating IGF system occur in multiple sclerosis (MS), a chronic inflammatory demyelinating disease of the central nervous system. We measured concentrations of IGF-I, IGF-II, and insulin-like growth factor binding proteins -1, -2, and -3 in both serum and cerebrospinal fluid from MS patients and age- and sex-matched controls. IGFBP-1 was not detectable in cerebrospinal fluid. We found no significant differences in any of the other components between patients with MS and controls.
    Neuroscience Letters 01/1999; 257(3):168-70. · 2.03 Impact Factor

Publication Stats

525 Citations
338.41 Total Impact Points

Institutions

  • 1977–2008
    • University of Groningen
      • • Department of Neurology
      • • Chemical Physics Group
      Groningen, Province of Groningen, Netherlands
  • 1973–2006
    • Universitair Medisch Centrum Groningen
      • • Department of Neurology
      • • Department of Internal Medicine
      Groningen, Groningen, Netherlands