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Biomedical subjects

H Butzkueven

Publications and source records attributed to H Butzkueven.

16 recordsLinked to original sources
PubMed2006

Short-term effects of methylprednisolone on cerebral volume in multiple sclerosis relapses.

We prospectively investigated the short-term effects of intravenous methyl-prednisolone (IVMP) on cerebral volume in patients suffering a multiple sclerosis (MS) relapse. Ten patients underwent MRI brain studies immediately before and after IVMP treatment, and 4 and 8 weeks later. Whole brain volumes decreased significantly over the 8-week period. The greatest change occurred during IVMP administration. This has implications for MS treatment trials using cerebral atrophy as an endpoint.

Adult↗
PubMed2006

Gait and balance impairment in early multiple sclerosis in the absence of clinical disability.

This study evaluated the gait and balance performance of two clinically distinct groups of recently diagnosed and minimally impaired multiple sclerosis (MS) patients (Expanded Disability Status Scale range 0-2.5), compared to control subjects. Ten MS patients with mild pyramidal signs (Pyramidal Functional Systems 1.0), 10 MS patients with no pyramidal signs (Pyramidal Functional Systems 0) and 20 age- and gender-matched control subjects were assessed using laboratory-based gait analysis and clinical balance measures. Both MS groups demonstrated reduced speed and stride length (P < 0.001), and prolonged double limb support (P <0.02), compared to the control group, along with alterations in the timing of ankle muscle activity, and the pattern of ankle motion during walking, which occurred independent of gait speed. The pyramidal MS group walked with reduced speed (P = 0.03) and stride length (P = 0.04), and prolonged double limb support (P =0.01), compared to the non-pyramidal group. Both MS groups demonstrated concomitant balance impairment, performing poorly on the Functional Reach Test compared to the control group (P <0.05). The identification of incipient gait and balance impairment in MS patients with recent disease onset suggests that motor function may begin to deteriorate in the early stages of the disease, even in the absence of clinical signs of pyramidal dysfunction.

Adult↗
PubMed2005

Oligodendrocytes exhibit selective expression of suppressor of cytokine signaling genes and signal transducer and activator of transcription 1 independent inhibition of interferon-gamma-induced toxicity in response to leukemia inhibitory factor.

Multiple sclerosis is an autoimmune disease of the CNS that results in the death of oligodendrocytes, the myelinating cells of the CNS. Previous studies have indicated that the cytokine leukemia inhibitory factor prevents the cytotoxic effects of interferon-gamma on oligodendrocytes in vitro, and the death of oligodendrocytes in an animal model of multiple sclerosis. Members of a recently characterized family of proteins, the suppressors of cytokine signaling, have been demonstrated to mediate negative cross-talk between cytokines, with induction of suppressors of cytokine signaling proteins by one cytokine inhibiting the activity of a second. Here, we assess whether induction of members of the suppressors of cytokine signaling family could explain the antagonistic biological effects of leukemia inhibitory factor and interferon-gamma upon oligodendrocytes. It is found that leukemia inhibitory factor rapidly and strongly induces the expression of suppressors of cytokine signaling-3 in cultured rat oligodendrocytes, whereas interferon-gamma weakly induces the expression of both suppressor of cytokine signaling-1 and 3. Pre-treatment of oligodendrocytes with leukemia inhibitory factor does not prevent the subsequent phosphorylation of signal transducer and activator of transcription-1 by interferon-gamma indicating that the leukemia inhibitory factor inhibition of interferon-gamma toxicity in oligodendrocytes is mediated by a suppressor of cytokine signaling-3 independent mechanism.

Animals↗
PubMed2005

Multiple Sclerosis Severity Score: using disability and disease duration to rate disease severity.

BACKGROUND: There is no consensus method for determining progression of disability in patients with multiple sclerosis (MS) when each patient has had only a single assessment in the course of the disease. METHODS: Using data from two large longitudinal databases, the authors tested whether cross-sectional disability assessments are representative of disease severity as a whole. An algorithm, the Multiple Sclerosis Severity Score (MSSS), which relates scores on the Expanded Disability Status Scale (EDSS) to the distribution of disability in patients with comparable disease durations, was devised and then applied to a collection of 9,892 patients from 11 countries to create the Global MSSS. In order to compare different methods of detecting such effects the authors simulated the effects of a genetic factor on disability. RESULTS: Cross-sectional EDSS measurements made after the first year were representative of overall disease severity. The MSSS was more powerful than the other methods the authors tested for detecting different rates of disease progression. CONCLUSION: The Multiple Sclerosis Severity Score (MSSS) is a powerful method for comparing disease progression using single assessment data. The Global MSSS can be used as a reference table for future disability comparisons. While useful for comparing groups of patients, disease fluctuation precludes its use as a predictor of future disability in an individual.

Adult↗
PubMed2004

LIF receptor signaling modulates neural stem cell renewal.

Activation of the leukemia inhibitory factor (LIF) receptor has been reported to promote gliogenesis and also to support neural stem cell (NSC) renewal. To investigate this paradox, we isolated NSCs and generated neurospheres from embryonic mice either wild-type, heterozygous, or homozygous null for LIF receptor (LIFR)-beta. Exogenous LIF abrogated neurosphere formation and promoted expression of GFAP by all cells in wild-type and heterozygous cultures. LIF also stimulated a twofold increase in the number of multipotential clones generated from these cultures in comparison with those pretreated with EGF and FGF-2 (E+F) alone. In contrast, the clonogenicity of low-density cultures of LIFR knockout cells was reduced in comparison with that of wild-type cells grown in E+F and was unaffected by LIF. Thus, although LIFR signaling is not necessary for NSC self-renewal, it enhances both the clonogenicity and the expression of GFAP by these multipotential cells.

Animals↗
PubMed2004

Serial MRI in multiple sclerosis: a prospective pilot study of lesion load, whole brain volume and thalamic atrophy.

Using serial magnetic resonance imaging (MRI), we investigated the relationship between diffuse cerebral atrophy, T1 and T2 lesion volumes, mean thalamic volumes and clinical progression in patients with established multiple sclerosis (MS). Eleven patients were included in this prospective serial study. Cerebral volumes, T1 hypointense lesion volumes, and T2 hyperintense lesion volumes at baseline and at up to 3 years follow-up were assessed on MRI brain scans. As a putative measure of cerebral atrophy mean thalamic volumes were also obtained. The outcome measures were the MRI parameters and disability on Kurtzke's expanded disability status scale (EDSS). Of the 11 patients 6 worsened clinically as measured by an increase of 0.5 or more on the EDSS. Cerebral atrophy occurred in 91% of patients and was independent of changes in lesion volumes and was not associated with disease progression as determined by the EDSS.

Adult↗
PubMed2003

Past exposure to sun, skin phenotype, and risk of multiple sclerosis: case-control study.

OBJECTIVE: To examine whether past high sun exposure is associated with a reduced risk of multiple sclerosis. DESIGN: Population based case-control study. SETTING: Tasmania, latitudes 41-3 degrees S. PARTICIPANTS: 136 cases with multiple sclerosis and 272 controls randomly drawn from the community and matched on sex and year of birth. MAIN OUTCOME MEASURE: Multiple sclerosis defined by both clinical and magnetic resonance imaging criteria. RESULTS: Higher sun exposure when aged 6-15 years (average 2-3 hours or more a day in summer during weekends and holidays) was associated with a decreased risk of multiple sclerosis (adjusted odds ratio 0.31, 95% confidence interval 0.16 to 0.59). Higher exposure in winter seemed more important than higher exposure in summer. Greater actinic damage was also independently associated with a decreased risk of multiple sclerosis (0.32, 0.11 to 0.88 for grades 4-6 disease). A dose-response relation was observed between multiple sclerosis and decreasing sun exposure when aged 6-15 years and with actinic damage. CONCLUSION: Higher sun exposure during childhood and early adolescence is associated with a reduced risk of multiple sclerosis. Insufficient ultraviolet radiation may therefore influence the development of multiple sclerosis.

Adolescent↗
PubMed2001

Neurotrophin receptor expression and responsiveness by postnatal cerebral oligodendroglia.

The low affinity neurotrophin receptor (p75(NTR)) is implicated in promoting oligodendrocytic death after nerve growth factor (NGF) stimulation but NGF and neurotrophin-3 (NT-3) can also potentiate oligodendrocytic survival. We show regional variability in p75(NTR) expression within the central nervous system of the postnatal rat; expression is readily detectable by immunohistochemistry upon a subset of CNPase-positive oligodendroglia in optic nerve but not within the cerebrum. Nevertheless, oligodendroglia isolated from the cerebrum and cultured for 16 hours express p75(NTR) as well as the trkC but not the TrkA gene. Viability was not, however, influenced by exposure to either NGF or NT-3. Cells overexpressing p75(NTR) remained unresponsive to NGF but exhibited potentiated survival with NT-3, correlating with the differential expression profile of their high affinity receptors.

Adenoviridae↗
PubMed2000

Onset seizures independently predict poor outcome after subarachnoid hemorrhage.

OBJECTIVE: To determine whether onset seizures after subarachnoid hemorrhage (SAH) carry independent prognostic information and to investigate the risk factors for late seizures after SAH. BACKGROUND: Modern management of SAH, including early operation, has substantially reduced mortality. No study has adequately assessed the importance of onset seizures in a contemporary SAH cohort. METHODS: The authors analyzed the records and initial CT scans of 412 consecutive patients with aneurysmal or nonaneurysmal SAH admitted to the Royal Melbourne Hospital from 1990 to 1996. Each patient with an onset seizure (n = 32, 7.8% of cohort) was age and sex matched to two nonseizure patients of the same cohort. Each patient with a late seizure (n = 17, 5.1% of cohort) was matched to five control subjects of the same cohort. RESULTS: With use of logistic regression analysis, onset seizures correlated with the sum score of blood on initial CT scan (OR = 1.1, p = 0.05), but there was no significant correlation with duration of loss of consciousness at onset, Glasgow Coma Score (GCS), presence of aneurysm, or past history of hypertension or epilepsy. Disability 6 weeks after SAH according to the Glasgow Outcome Scale was independently predicted by initial GCS of <6 (OR = 13.7, p < 0.01) and onset seizure (OR = 7.8, p = 0.04). Late seizures within the first 6 weeks were independently related to rebleeding (OR = 94, p < 0.01) and onset seizures (OR = 27, p < 0.01) but not to other onset variables, development of hydrocephalus, or vasospasm. CONCLUSION: In this single-institution cohort of patients with SAH, onset seizures were an independent risk factor for late seizures and a predictor of poor outcome.

Female↗
PubMed2000

Treatment of experimental autoimmune encephalomyelitis with antisense oligonucleotides against the low affinity neurotrophin receptor.

Upregulated expression of the low-affinity neurotrophin receptor (p75) in the central nervous system (CNS) during experimental autoimmune encephalomyelitis (EAE) has recently been demonstrated. To investigate whether p75 plays a role in disease pathogenesis, we adopted a gene therapy approach, utilizing antisense oligonucleotides to downregulate p75 expression during EAE. Phosphorothioate antisense oligonucleotides (AS), nonsense oligonucleotides (NS) or phosphate buffered saline (PBS) were injected daily for 18 days after immunization of SJL/J (H-2s)-mice with myelin proteolipid protein (PLP) peptide 139-151. In the AS group, there was a statistically significant reduction in both the mean maximal disease score (1.85 in the AS, 2.94 in the NS and 2.75 in the PBS-groups, respectively, P < 0.025) and in the cumulative disease incidence ( approximately 60% in the AS group and approximately 90% in the control groups). Histological and immunohistochemical analysis showed reduced inflammation and demyelination, as well as reduced p75 expression at the blood-brain barrier (BBB) in the AS-treated mice in comparison with both control groups. There was no difference, however, in p75 expression on neural cells within the CNS between the three groups of mice. We conclude that p75 could play a proactive role in the pathogenesis of EAE and may exert its effect at the level of the BBB.

Animals↗
PubMed2000

Nitrous oxide myelopathy in an abuser of whipped cream bulbs.

A 23 year old man presented with a severe posterior column myelopathy related to prolonged nitrous oxide abuse obtained from whipped cream bulbs. The site of pathology was identified by magnetic resonance imaging (MRI) and somatosensory evoked potentials. The mechanism of toxicity involves inactivation of vitamin B12 dependent enzymes. Appropriate treatment with methionine and vitamin B12 was instituted quickly with good neurological outcome. There are major concerns regarding the availability of nitrous oxide in supermarkets.

Adult↗
PubMed1999

Combined peripheral nerve and central nervous system demyelination in a patient with chronic inflammatory demyelinating polyneuropathy.

We report the case of a 49-year-old woman suffering combined central and peripheral demyelination, with serial magnetic resonance images scans illustrating the development of central demyelination in a patient with established chronic inflammatory demyelinating polyneuropathy. This is the sixth patient with this rare overlap syndrome reported to date. We review the available literature and argue that an inherited predisposition to both diseases is the most likely explanation for its occurrence. Copyright 1999 Harcourt Publishers Ltd.

Journal Article↗
PubMedDate not supplied

Cladribine followed by autologous stem-cell transplantation in progressive multiple sclerosis.

We studied the safety of autologous peripheral blood stem-cell transplantation (PBSCT) in four patients with progressive multiple sclerosis. Clinical and magnetic resonance imaging outcomes were secondary end-points. Cladribine administration preceded filgrastim-primed PBSC collection, aiming for lymphocyte depletion. Conditioning was with antithymocyte globulin and cyclophosphamide. The procedure was well tolerated, but without obvious clinical benefit. The study was terminated when other therapeutic options with lower morbidity became available.

Adult↗