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Biomedical subjects

J De Keyser

Publications and source records attributed to J De Keyser.

At least 37 records · Page 2Linked to original sources
PubMed2000

Insulin-like growth factor II receptors in human brain and their absence in astrogliotic plaques in multiple sclerosis.

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.

Aged↗
PubMed2000

Astrocytes in chronic active multiple sclerosis plaques express MHC class II molecules.

To initiate the inflammatory cascade leading to demyelination in multiple sclerosis (MS) T cells have to recognize their specific myelin antigen, which needs to be presented in the context of major histocompatibility (MHC) class II molecules expressed on antigen presenting cells. Whether astrocytes can express MHC class II molecules in vivo is a controversial issue. We performed double labeling immunohistochemistry in postmortem samples from nine patients with MS, three patients with a cerebral infarction and six controls. Astrocytes in controls, in normal appearing white matter in MS, and at the boundary of infarctions were MHC class II negative. In contrast, a subset of astrocytes in active chronic plaques immunostained for MHC class II, indicating potential antigen presenting interactions of astrocytes in MS.

Aged↗
PubMed2000

Predicting outcome from coma: man-in-the-barrel syndrome as potential pitfall.

The Glasgow coma scale motor score is often used in predicting outcome after hypoxic-ischemic coma. Judicious care should be exerted when using this variable in predicting outcome in patients with coma following hypotension since borderzone infarction can obscure the clinical picture. We describe a patient who underwent skull base surgery for a schwannoma of the left facial nerve. The operation, which lasted for 10 h, was conducted under controlled hypotension. After the intervention the patient remained comatose with absent arm movements upon painful stimuli. An absent motor score usually carries a poor prognosis. However, magnetic resonance inversion recovery imaging of the brain showed bilateral hyperintense lesions in the arm-hand area indicative of borderzone ischemic damage. The patient received optimal supportive care and after 17 days he regained consciousness with 'man-in-the-barrel syndrome', which also further improved over time.

Coma↗
PubMed1999

Astrocytes in multiple sclerosis lack beta-2 adrenergic receptors.

BACKGROUND: In MS, T cells reactive to myelin proteins can cross the blood-brain barrier and release proinflammatory cytokines, such as interferon gamma. These can induce glial cells to express class II major histocompatibility complex (MHC) molecules, which are required to present myelin antigens to the T cells in order to mount a proper autoimmune response. Both microglia and astrocytes can function as antigen-presenting cells. In contrast to microglia, endogenous suppressors, including norepinephrine, regulate astrocytic class II MHC expression. The effects of norepinephrine are mediated through activation of P2 adrenergic receptors. OBJECTIVE: To investigate P, adrenergic receptors in astrocytes in MS. METHODS: Immunocytochemical techniques were applied in postmortem brain tissue from 10 patients with MS, three patients with a cerebral infarction, and six controls, and in spinal cord from three patients with ALS. RESULTS: beta2 adrenergic receptors were visualized on astrocytes in white matter of controls, and they were prominently expressed in reactive astrocytes at the boundary of cerebral infarctions and in the lateral corticospinal tract in ALS. In MS, beta2 adrenergic receptors could neither be visualized on astrocytes in normal-appearing white matter nor in reactive astrocytes in chronic active and inactive plaques, whereas they were normally present on neurons. MHC class II-positive astrocytes were only visualized in chronic active plaques. CONCLUSIONS: Because astrocytic beta2 adrenergic receptors are involved in suppressing inducibility of MHC class II molecules, we suggest that their lack of expression may play an important role in the induction or perpetuation of autoimmune reactions in MS.

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PubMed1999

Peptidylarginine deiminase activity in postmortem white matter of patients with multiple sclerosis.

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.

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PubMed1999

From stroke unit care to stroke care unit.

In some stroke units continuous monitoring of blood pressure, electrocardiogram, body temperature, and oxygen saturation has become an integral part of the management of acute stroke. In addition, regular measurements of blood glucose are performed. Stroke units equipped with such monitoring facilities should be named 'stroke care units' by analogy with coronary care units. The goal of a stroke care unit is early detection and rapid correction of extracranial factors which may aggravate cerebral damage in ischemic brain, including hypoxia, hyperglycemia, hypotension, cardiac arrhythmias, and elevated body temperature.

Cerebrovascular Disorders↗
PubMed1999

Clinical trials with neuroprotective drugs in acute ischaemic stroke: are we doing the right thing?

Ischaemic stroke is a leading cause of death and long-lasting disability. Several neuroprotective drugs have been developed that have the potential to limit ischaemic brain damage and improve outcome for patients. While promising results with these drugs have been achieved in animal stroke models, all Phase III trials conducted so far indicate that these drugs have failed to live up to their promise. Despite the limits of animal models, which cannot mimic the clinical situation, the disappointing results of neuroprotective trials might largely be due to methodological problems. Future trials with neuroprotective drugs should be performed in stroke (care) units, after sufficient information regarding therapeutic time window, dosage, duration of therapy and safety has been gathered from pilot studies, and a better selection of target patients has been made. Much of this information can now be obtained by techniques that visualize the penumbra, such as combined diffusion-weighted and perfusion MRI. Consideration should also be given to clinical trials with well-designed combinations of treatments.

Brain Ischemia↗
PubMed1999

Management of acute ischaemic stroke.

Over the past few years there have been enormous changes in the management of stroke patients. General practitioners, ambulance personnel/paramedics and the general public need to be well informed that stroke is a medical emergency. Prevention of secondary brain damage by normalising vital parameters and combating fever should already start at the scene or in the ambulance. Early recognition of stroke symptoms, immediate transfer to a suitable treatment facility, and rapid in hospital triage protocols should bring thrombolysis to a larger number of stroke victims. Admission to a unit that is dedicated to the care of stroke patients helps to reduce mortality and morbidity.

Brain Ischemia↗
PubMed1999

Use of the Barthel index and modified Rankin scale in acute stroke trials.

BACKGROUND AND PURPOSE: The Barthel Index (BI) and the Modified Rankin Scale (MRS) are commonly used scales that measure disability or dependence in activities of daily living in stroke victims. The objective of this study was to investigate how these scales were used and interpreted in acute stroke trials. METHODS: We identified from MEDLINE the major efficacy trials with neuroprotective drugs, thrombolytic drugs, and anticoagulants in acute ischemic stroke published between January 1995 and December 1998. We selected those trials that used the BI and/or MRS as outcome parameters. RESULTS: Fifteen trials fulfilling the inclusion criteria were identified. The BI was used in 13 and the MRS in 8. In 4 trials mean and median scores of the BI were used, and in 1 trial median scores of the MRS were compared. Primary end points included the BI in 7, the MRS in 6, and both the BI and MRS in 3. With regard to the BI, a variety of sum scores between 50 and 95 were used as cutoff scores to define favorable outcome. Favorable outcome on the MRS was defined as either </=1 or </=2. CONCLUSIONS: Among the efficacy trials in acute stroke, we found remarkable differences in the choice of primary end points and in the definition of favorable outcome on both the BI and MRS. This lack of consensus strongly hinders the design, interpretation, and comparison of acute stroke trials. In general, it may be easier to define poor outcome instead of favorable outcome. Poor outcome could be defined if any of the following end points are reached: death, institutionalization due to stroke, MRS >3, or BI <60.

Acute Disease↗
PubMed1998

Insulin-like growth factor system in serum and cerebrospinal fluid in patients with multiple sclerosis.

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.

Adult↗
PubMed1998

Increased serum neuron specific enolase concentrations in patients with hyperglycemic cortical ischemic stroke.

A detrimental effect of hyperglycemia in ischemic brain has been demonstrated in laboratory experiments and it has been found that hyperglycemia in ischemic stroke is a predictor of poor outcome. We determined serum neuron specific enolase (NSE) concentrations in 41 consecutive patients with a cerebral hemispheric stroke between 12 and 24 h after stroke onset. In cortical ischemic strokes complicated by hyperglycemia (blood glucose concentration > 7 mmol/l) we found significantly higher NSE levels than in normoglycemic patients. In lacunar ischemic strokes NSE levels were not significantly different between normoglycemic and hyperglycemic patients. Our findings support the concept that hyperglycemia during acute cortical ischemic stroke is associated with enhanced neuronal cell death.

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PubMed1998

Effects of influenza vaccination and influenza illness on exacerbations in multiple sclerosis.

Despite reports that influenza vaccination appears to be safe in multiple sclerosis there is uncertainty which patients may benefit from it. By using a questionnaire we compared the effects of influenza illness (1995-1996 season) and influenza vaccination (autumn of 1996) on neurologic symptoms in patients with multiple sclerosis registered in the Groningen Multiple Sclerosis Data Bank. No clinically relevant effects were reported in 53 patients with primary progressive multiple sclerosis, either following vaccination or the illness. In a group of 180 patients with relapsing multiple sclerosis, an exacerbation occurred within the following 6 weeks in 33% after influenza illness, whereas it occurred in only 5% after vaccination. The exacerbation rate following influenza illness was significantly higher regardless of whether patients were essentially restricted to wheelchair or not. Because of a substantial greater risk of relapse after influenza illness than after vaccination, annual influenza vaccination should be offered routinely to all patients with relapsing multiple sclerosis.

Adult↗
PubMed1997

Insulin-like growth factor-I receptors in normal appearing white matter and chronic plaques in multiple sclerosis.

Preclinical studies suggest that insulin-like growth factor-I (IGF-I) plays an important role in oligodendrocyte survival and myelination. We used human recombinant [125I]IGF-I to study IGF-I receptors in post-mortem brain tissue from patients with multiple sclerosis (MS). In normal appearing white matter, we found that IGF-I receptor densities and binding characteristics were not different between MS patients and controls. In chronic plaques, histologically characterized by astrogliosis, we found densities of IGF-I receptors which were in the same range as those measured in the normal appearing white matter. In vitro studies have shown that IGF-I also acts as a mitogenic factor for astrocytes. Since MS lesions are rapidly invaded by reactive astrocytes, IGF-I may not only protect oligodendrocytes and stimulate remyelination but also enhance the astrogliosis that limits repair.

Aged↗