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Biomedical subjects

J De Keyser

Publications and source records attributed to J De Keyser.

At least 19 recordsLinked to original sources
PubMed2006

Benign course in multiple sclerosis: a review.

Since the 1950s, it has been recognized that a subgroup of multiple sclerosis (MS) patients exists that shows little or no progression in the severity of the disease over time. This group is referred to as 'benign' MS. Although a substantial amount of research in MS indicates a multifactorial background in disease severity, to date it is still difficult to predict whether the course will be benign at onset and it is difficult to find factors that influence the course of the disease over time. Maintaining or restoring neural conduction inside a central nervous system lesion seems to be the essence of staying 'benign'.

Axons↗
PubMed2006

Plasma homocysteine levels in multiple sclerosis.

BACKGROUND: There is evidence that homocysteine contributes to various neurodegenerative disorders, and elevated plasma homocysteine levels have been observed in patients with multiple sclerosis (MS). OBJECTIVE: To investigate if and why plasma homocysteine levels are increased in MS, and whether they play a role in the disease course. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Aged↗
PubMed2005

A randomized crossover study of bee sting therapy for multiple sclerosis.

BACKGROUND: Bee sting therapy is increasingly used to treat patients with multiple sclerosis (MS) in the belief that it can stabilize or ameliorate the disease. However, there are no clinical studies to justify its use. METHODS: In a randomized, crossover study, we assigned 26 patients with relapsing-remitting or relapsing secondary progressive MS to 24 weeks of medically supervised bee sting therapy or 24 weeks of no treatment. Live bees (up to a maximum of 20) were used to administer bee venom three times per week. The primary outcome was the cumulative number of new gadolinium-enhancing lesions on T1-weighted MRI of the brain. Secondary outcomes were lesion load on T2*-weighted MRI, relapse rate, disability (Expanded Disability Status Scale, Multiple Sclerosis Functional Composite, Guy's Neurologic Disability Scale), fatigue (Abbreviated Fatigue Questionnaire, Fatigue Impact Scale), and health-related quality of life (Medical Outcomes Study 36-Item Short Form General Health Survey). RESULTS: During bee sting therapy, there was no significant reduction in the cumulative number of new gadolinium-enhancing lesions. The T2*-weighted lesion load further progressed, and there was no significant reduction in relapse rate. There was no improvement of disability, fatigue, and quality of life. Bee sting therapy was well tolerated, and there were no serious adverse events. CONCLUSIONS: In this trial, treatment with bee venom in patients with relapsing multiple sclerosis did not reduce disease activity, disability, or fatigue and did not improve quality of life.

Adult↗
PubMed2005

Characterizing the mechanisms of progression in multiple sclerosis: evidence and new hypotheses for future directions.

Major advancements have been achieved in our ability to diagnose multiple sclerosis (MS) and to commence treatment intervention with agents that can favorably affect the disease course. Although MS exacerbations and the emergence of disability constitute the more conspicuous aspects of the disease process, evidence has confirmed that most of the disease occurs on a constitutive and occult basis. Disease-modifying therapies appear to be modest in the magnitude of their treatment effects, particularly in the progressive stage of the disease. Therapeutic strategies currently used for MS primarily target the inflammatory cascade. Several potential mechanisms appear to be involved in the progression of MS. Characterizing these mechanisms will result in a better understanding of the various forms of the disorder and how to effectively treat its clinical manifestations. It is our objective within this 2-part series on progression in MS to offer both evidence-based observations and hypothesis-driven expert perspectives on what constitutes the cause of progression in MS. We have chosen areas of inquiry that appear to have been most productive in helping us to better conceptualize the landscape of what MS looks like pathologically, immunologically, neuroscientifically, radiographically, and genetically. We have attempted to advance hypotheses focused on a deeper understanding of what contributes to the progression of this illness and to illustrate new technical capabilities that are catalyzing novel research initiatives targeted at achieving a more complete understanding of progression in MS.

Disease Progression↗
PubMed2005

Serum uric acid, dehydroepiandrosterone sulphate, and apolipoprotein E genotype in benign vs. progressive multiple sclerosis.

The majority of patients with multiple sclerosis (MS) experience gradual progression of disability, either as secondary progressive MS (SPMS) or primary progressive MS (PPMS). A subgroup with relapsing-remitting MS shows a benign course with little or no disease progression and minimal disability decades after the first manifestations, so called benign MS (BMS). In our search to identify factors that are associated with progression of MS, we investigated serum levels of uric acid and dehydroepiandrostenedione sulphate (DHEAS), and apolipoprotein (apo)E genotype in 28 patients with BMS, 33 with SPMS, 21 with PPMS, and 29 healthy individuals. We found no significant changes in uric acid levels and apoE genotype between the four groups. Mean DHEAS levels were lower in MS patients compared with healthy controls (P = 0.049), but there were no significant differences between the clinical subgroups of MS. In patients with SPMS and PPMS there was no correlation between progression rate and serum levels of either uric acid or DHEAS. Our results suggest that serum levels of uric acid and DHEAS, and apoE genotype do not differ between patients with a benign and progressive course of MS.

Adult↗
PubMed2005

Efficacy of desmopressin in patients with multiple sclerosis suffering from bladder dysfunction: a meta-analysis.

OBJECTIVES: The current review evaluates the safety and efficacy of desmopressin in patients with multiple sclerosis (MS) who suffer from both daytime and nocturnal voiding frequency and from incontinence. MATERIALS AND METHODS: A literature search was carried out looking for studies published between 1990 and 2003 which evaluated desmopressin in MS patients with bladder dysfunction. RESULTS: The grand total mean effect sizes show the following estimates of clinical relevant differences: desmopressin has a moderate effect on the number of voids during the day or during the night over a period of 6 h after taking the drug. A large effect associated with the use of desmopressin was detected by the mean difference in urine volume (ml) in 6 h. A small effect was detected in the mean 24-h urine volume. Serum sodium levels were combined with plasma osmolality in some studies and were found to be not significantly affected by desmopressin treatment.

Adult↗
PubMed2005

Serum levels of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 in relapsing and primary progressive multiple sclerosis.

Using radioimmunoassay we measured serum levels of insulin-like growth factor (IGF)-1 and IGF binding protein (IGFBP)-3 in patients with relapsing multiple sclerosis (MS) and a benign course (Expanded Disability Status Scale (EDSS) < or =3 despite > 10 years disease duration), relapsing MS with cumulative disability leading to an EDSS score >4 within 10 years of disease duration, primary progressive MS and healthy controls. We found no differences in IGF-1 and IGFBP-3 serum levels, and the IGF-1/IGFBP-3 ratio between the four groups. However, there was a significant correlation (P =0.005) between IGFBP-3 serum levels and both the progression index of disability and the Multiple Sclerosis Severity Score in patients with primary progressive MS.

Adult↗
PubMed2004

Insulin-like growth factor binding protein-4 interacts with centrosomes and microtubules in primary astrocytes.

Insulin-like growth factor-1 and -2 (IGFs) are important for CNS development and have implications in pathological situations of the brain. Insulin-like growth factor binding protein-4 (IGFBP-4) regulates the biological effects of IGFs. We examined the expression of IGFBP-4 in primary rat and human astrocytes. IGFBP-4 mRNA was detectable by reverse transcription-polymerase chain reaction (RT-PCR) and protein expression was verified by Western blotting of cell lysates as well as conditioned culture medium. When astrocytes were immunostained for IGFBP-4 we detected an intracellular structure that did not derive from organelles involved in cellular trafficking. Ingestion of fluorescein isothiocyanate-labeled transferrin excluded detection of IGFBP-4 within vesicles of endosomal nature, in which the protein might have been incorporated. Double staining with gamma-tubulin demonstrated co-localization of IGFBP-4 with centrosomes of these cells. Treatment with nocodazole resulted in absence of IGFBP-4 signal on centrosomes, indicating a dependency on intact microtubules. Immunoelectron microscopy revealed IGFBP-4 localization not only at the centrioles but also a direct interaction with microtubules. There was no binding of IGFBP-4 to centrioles in primary rat oligodendrocytes, microglia or meningeal cells. The association of IGFBP-4 with centrioles and microtubules in astrocytes suggests an involvement of this molecule in microtubule functions of these cells.

Animals↗
PubMed2003

Low leucocyte myeloperoxidase activity in patients with multiple sclerosis.

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.

Adult↗
PubMed2001

Cooling garment treatment in MS: clinical improvement and decrease in leukocyte NO production.

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.

Adult↗
PubMed2001

Disappearance of beta2-adrenergic receptors on astrocytes in canine distemper encephalitis: possible implications for the pathogenesis of multiple sclerosis.

It has been reported that astrocytes in the white matter of patients with multiple sclerosis (MS) lack beta2-adrenergic receptors. This abnormality might explain why astrocytes in active MS plaques aberrantly express major histocompatibility (MHC) class II molecules, which play an important role in the immunological cascade leading to myelin destruction. Canine distemper (CD) virus primarily infects astrocytes and causes a demyelinating disease in dogs that closely resembles MS. In control dogs, including three dogs with another inflammatory disease, beta2-adrenergic receptor immunoreactivity was observed on both neurons and astrocytes. In dogs with CD encephalitis, beta2-adrenergic receptors were present on neurons, but were absent on astrocytes in acute lesions, demyelinated lesions, and normal-appearing white matter. Similar to MS, several astrocytes in demyelinated lesions expressed MHC class II. These findings suggest that MS and the demyelinating stages of CD encephalitis have a common pathogenetic factor, and that the loss of astrocytic beta2-adrenergic receptors in MS might be induced by a viral infection of astrocytes.

Animals↗
PubMed2001

Mapping of a susceptibility gene for multiple sclerosis to the 51 kb interval between G511525 and D6S1666 using a new method of haplotype sharing analysis.

Multiple sclerosis (MS) is a complex disease that is partly genetic in origin. Although an association of MS with specific human leukocyte antigen (HLA) types has been known for almost 30 years, the nature of this relationship has remained unclear. Furthermore, genetic resolution sufficient to implicate a specific gene in the HLA region has not been achieved. Many loci in the HLA region have been found to be significantly associated with MS, which is largely explained by the extended haplotype sharing and varying marker informativity of the region. We have determined 248 haplotypes of MS patients from the population of the northern Netherlands and 226 haplotypes of their relatives as controls using a set of 22 microsatellite markers covering the HLA region. The data were analyzed using standard association methods and a new statistical method, haplotype sharing statistics (HSS). Haplotype sharing statistics determines the extent of haplotype sharing for all pairs of haplotypes of patients and of controls and calculates the difference in mean haplotype sharing between patients and controls. Haplotype sharing was found to be significantly greater among patients than among controls in a region of 1.1 Mb between markers G511525 and TNFalpha. The involvement of this region is also supported by association analysis and the transmission/disequilibrium test (TDT). Within this region, HSS, which is largely independent of association and TDT, indicated the interval of 51 kb between G511525 and D6S1666 as that most likely to contain a susceptibility gene for MS. As DQB1 is the sole gene known in this interval at present, the results of our analysis suggest that this gene plays a role in the pathogenesis of MS.

Cluster Analysis↗
PubMed2001

Early prediction of a benign course of multiple sclerosis on clinical grounds: a systematic review.

BACKGROUND: There is growing consensus that neurologists should consider disease-modifying therapies early in multiple sclerosis (MS). However, there is a subgroup with a natural benign course, in which treatment could be postponed. We sought to determine the frequency of benign MS and early clinical factors that may predict a benign course. METHODS: We performed a systematic review of the existing literature on benign MS, which was defined as minimal or no disability equivalent to a score on the Expanded Disability Status Scale (EDSS) < or = 3.0 at least 10 years after disease onset RESULTS: Only a small number of studies of adequate quality was available. In total there were nine published studies representing 2,204 patients. The estimated frequency of benign MS was 26.7%. Onset with optic neuritis, onset before the age of 40 years, absence of pyramidal signs at presentation, duration of first remission more than 1 year, and only one exacerbation in the first 5 years after onset of MS, were associated with a benign course. CONCLUSIONS: From the existing literature a set of unrelated clinical characteristics emerged that was associated with a benign course of MS. However, there is a need for prospective studies to define more precisely clinical and paraclinical predictors of benign MS.

Disability Evaluation↗
PubMed2000

Comparison of serum S-100 protein levels following stroke and traumatic brain injury.

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.

Adult↗
PubMed2000

Continuous pulse oximetry in acute hemiparetic stroke.

BACKGROUND AND PURPOSE: Hypoxemia can adversely affect ischemic brain tissue in laboratory animals. The aim of this study was to assess the value of early continuous monitoring with pulse oximetry in detecting arterial oxygen desaturations in patients with acute hemiparetic stroke, and the effects of oxygen administration. METHODS: Over a period of 6 months 49 consecutive patients with acute hemiparetic stroke of </=12 h duration were monitored for the first 48 h with pulse oximetry. Patients in whom arterial oxygen saturation (SaO(2)) fell beneath 96% for a period longer than 5 min were treated with oxygen administered via nasal prongs or oxygen mask. RESULTS: Thirty-one patients (63.3%) developed arterial oxygen desaturations. Of these patients 28 could effectively be treated with oxygen up to a flow-rate of 5 l/min. Only 3 patients required higher oxygen concentrations from 6 to 10 l/min. No acute adverse effects of oxygen treatment were observed. All patients with a history of cardiac and pulmonary disease developed drops in SaO(2). The occurrence of arterial oxygen desaturations was related to stroke severity (P=0.024), the presence of dysphagia (P=0.047), and older age (P=0.037). CONCLUSION: Patients with acute hemiparetic stroke frequently develop arterial oxygen desaturations. Continuous monitoring with pulse oximetry in this group of patients is a simple and useful method to detect drops in SaO(2) and to titrate oxygen administration.

Acute Disease↗
PubMed2000

[3H]dihydroalprenolol binding to beta adrenergic receptors in multiple sclerosis brain.

By using immunocytochemistry we previously reported the absence of beta(2) adrenergic receptors on astrocytes in multiple sclerosis (MS) white matter. Here, we measured beta(1) and beta(2) adrenergic receptor concentrations in postmortem brain sections of six MS patients and six controls by using quantitative autoradiography with [(3)H]dihydroalprenolol. White matter contained no beta(1) adrenergic receptors. In white matter of controls low levels of beta(2) adrenergic receptors were detected. In agreement with the immunohistochemical study, we were unable to detect beta(2) adrenergic receptors in both normal appearing white matter and astrogliotic plaques in MS. Concentrations of beta(1) and beta(2) adrenergic receptors in cerebral cortex were not different between controls and MS patients.

Adrenergic beta-Antagonists↗