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  • 1
    Electronic Resource
    Electronic Resource
    HLA-DRB1 * 03, but not the TNFA -308 promoter gene polymorphism, confers protection against fistulising Crohn’s disease (1998)
    Springer
    Immunogenetics 47 (1998), S. 451-455 
    Details
    ISSN: 1432-1211
    Keywords: Key words Crohn’s disease ; Fistula ; HLA association ; DRB1 ; TNF polymorphism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract  Crohn’s disease (CD) appears in forms so diverse that it has been hypothesized CD might be a syndrome, with different pathogenic mechanisms leading to the various clinical phenotypes. This may plausibly explain the conflicting and inconclusive results with regard to HLA associations in unselected groups of patients. The power of these association studies may increase when disease heterogeneity is taken into account. As fistulising CD has been proposed as a separate subgroup of patients with CD, we studied the carrier frequencies (CF) of the DRB1 alleles in 35 unrelated Caucasian Dutch CD patients with proven peri-anal fistulas. A striking decrease in the frequency of the DRB1 * 03 allele was found in those patients with peri-anal fistulas when compared with a panel of 2400 healthy controls (HC) (3% vs 25%; P = 0.005; Odds Ratio [OR] = 0.09). The DRB1 * 03 allele is in strong linkage disequilibrium with a polymorphism at position –308 in the promoter region of the gene encoding TNFα (TNFA-308 * 2). We investigated whether this allele frequency was decreased as well. Surprisingly, the CF of TNFA-308 * 2 was 29%, not different from the CF of 98 HC (34%; P = 0.7; OR = 0.8). This study is the first showing a significant negative association between DRB1 * 03 and a particular subgroup of CD patients. Thus, patient selection may largely determine the outcome of genetic association studies in CD, as we previously observed no association with this allele in an unselected population of CD patients. As DRB1 * 03 frequency, but not the closely linked TNFA-308 * 2, was decreased, this suggests recombination between the DRB1 and TNFA loci in this group of patients, and may help to define the biological basis of fistula formation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002510050382
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  • 2
    Electronic Resource
    Electronic Resource
    Comparison of two Types of Surgery for Thoraco-Lumbar Burst Fractures: Combined Anterior and Posterior Stabilisation vs. Posterior Instrumentation Only (1999)
    Springer
    Acta neurochirurgica 141 (1999), S. 349-357 
    Details
    ISSN: 0942-0940
    Keywords: Keywords: Thoraco lumbar spinal fractures; outcome; surgical technique; spinal instrumentation.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary  This retrospective study compares clinical outcome following two different types of surgery for thoracolumbar burst fractures. Forty-six patients with thoracolumbar burst fractures causing encroachment of the spinal canal greater than 50% were operated on within 30 days performing either: combined anterior decompression and stabilisation and posterior stabilisation (Group 1) or posterior distraction and stabilisation using pedicle instrumentation (AO internal fixator) (Group 2). We evaluated: neurological status (Frankel Grade), spinal deformities, residual pain, and complications. The average follow-up was 6 years. There were no significant differences between the patients in both groups concerning age, sex, cause of injury and the presence of other severe injuries. Neurological dysfunction was present in 39% of all cases. Bony union occurred in all patients. Loss of reduction greater than 5 degrees and instrumentation failure occurred significantly more often in Group 2 compared to Group 1, but the kyphosis angle at late follow-up did not differ between groups, due to some degree of overcorrection initially after surgery in Group 2. The clinical outcome was similar in both groups, and all but one patient with neurological deficits improved by at least one Frankel grade.  Indirect decompression of the spinal canal by posterior distraction and short-segment stabilisation with AO internal fixator is considered appropriate treatment for the majority of unstable thoracolumbar burst fractures. This is a less extensive surgical procedure than a combined anterior and posterior approach.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s007010050310
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  • 3
    Electronic Resource
    Electronic Resource
    Tumours of the thalamic region (1987)
    Springer
    Acta neurochirurgica 85 (1987), S. 125-127 
    Details
    ISSN: 0942-0940
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Twenty seven patients with thalamic tumours were evaluated retrospectively in the Neurosurgical Clinic of the University Hospital in Groningen between 1969 and 1983. The diagnosis was based on neuroradiological studies. The authors recommend stereotactic biopsy of thalamic tumours followed by irradiation in selected cases.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01456108
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  • 4
    Electronic Resource
    Electronic Resource
    A NFKB1 promoter polymorphism is involved in susceptibility to ulcerative colitis (2005)
    Oxford, UK : Blackwell Science Ltd
    International journal of immunogenetics 32 (2005), S. 0 
    Details
    ISSN: 1744-313X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: Nuclear factor κB (NF-κB) designates a group of critical transcription factors involved in a variety of immunologic and/or inflammatory processes. Conceivably, genes involved in the NF-κB pathway make interesting candidate genes for chronic inflammatory disorders, including the inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC). In two mouse models of colitis, strong linkage has been observed with a locus on chromosome 3 that harbours the Nfkb1 gene. In addition, a polymorphism in the promoter region of the human NFKB1 gene was found to be associated with susceptibility to UC. In this study, we searched to confirm this previously found association in IBD in a different population. Allele and genotype frequencies of the −94 ins/delATTG polymorphism were determined in 266 unrelated Dutch Caucasian IBD patients (127 UC, 139 CD), and 155 matched healthy controls. The allele frequency of the deletion was significantly higher in UC patients (P = 0.019), but not in CD patients, compared to healthy controls, and the UC patients homozygous for the −94 ATTG deletion had a younger age of onset. Our findings confirm the previously found association between this polymorphism and susceptibility to UC in an independent study population and adds further evidence for the role of this gene in disease susceptibility.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1744-313X.2005.00546.x
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  • 5
    Electronic Resource
    Electronic Resource
    A critical approach to new forms of treatment of Crohn's disease and ulcerative colitis (2002)
    Oxford, UK : Blackwell Science, Ltd
    Alimentary pharmacology & therapeutics 16 (2002), S. 0 
    Details
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Most patients with inflammatory bowel disease can be managed with conventional immunosuppressive therapy. The choice of agents to prevent relapses of inflammatory bowel disease must be based on efficacy, toxicity and cost. Studies in animal models of inflammatory bowel disease indicate that chronic intestinal inflammation results from enhanced immune responses to bacteria that are present normally in the lumen. Loss of tolerance, an abnormal function or defective healing of the mucosal barrier may all give raise to chronic intestinal inflammation. This hypothesis is the basis of new therapies aimed at either decreasing the levels of luminal bacterial antigens and/or selectively blocking detrimental mucosal immune responses. Anti-TNF is an example of this novel approach that is very effective in Crohn's disease. The use of biological therapy is costly, however, and the long-term complications are not yet known. The recent increase of tuberculosis in patients treated with anti-TNF indicates that careful monitoring is necessary. It is clear that the new forms of treatment may play an important role in tailoring the appropriate drug to a specific group of patients. However, for the time being, fine-tuning in the use of conventional immunosuppression is necessary. New knowledge in the pharmacogenetics of these compounds allows improvements to be made in their use. It is to be hoped that a critical approach in the use of current and future drugs, taking into account the advances in the aetiopathogenesis of inflammatory bowel disease, will contribute to the quality of life of patients with inflammatory bowel disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2036.16.s4.8.x
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  • 6
    Electronic Resource
    Electronic Resource
    Secretion of Tumour Necrosis Factor α and Lymphotoxin α in Relation to Polymorphisms in the TNF Genes and HLA-DR Alleles. Relevance for Inflammatory Bowel Disease (1996)
    Oxford, U.K. and Cambridge, USA : Blackwell Science Ltd
    Scandinavian journal of immunology 43 (1996), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The genes for tumour necrosis factor alpha (TNFα) and lymphotoxin alpha (LTα; TNFβ) are tandemly arranged in the central region of the MHC. They may, therefore, be of importance for the aetiology of MHC-associated diseases. The authors have prospectively studied the secretion of TNFα and LTα in relation to polymorphisms at positions -308 and -238 in the TNFα gene (TNFA), and two polymorphisms in the first intron of the LTα gene (LTA), as well as HLA-DR in 30 patients with chronic inflammatory bowel diseases (IBD) and 12 healthy controls. In the Dutch population, the alleles of these four polymorphisms are present in only five combinations, called TNF-haplotypes: TNF-C, -E, -H, -I, and -P. Significant associations between TNF haplotypes and TNFα and LTα secretion were found when PBMC were cultured with T-cell activators, irrespective of disease. Mean TNFα secretion of individuals carrying the HLA-DR3 associated TNF-E haplotype was significantly higher, as compared to individuals without this haplotype (26 441 pg/ml versus 19 629 pg/ml; P = 0.014). Individuals carrying the TNF-C haplotype produced the lowest amount of TNFα (17 408 pg/ml; P = 0.022). The TNF-C and TNF-E haplotypes differ only at position -308 in the promoter of TNFA. Individuals carrying the HLA-DR1 associated TNF-I haplotype produced significantly less LTα when compared to those who lack this haplotype (1979 pg/ml versus 3462 pg/ml; P = 0.006). As the TNF-I haplotype is also associated with low TNFα secretion, this haplotype thus defines a ‘low secretor phenotype’. In conclusion, this is the first study to show associations between TNF haplotypes and TNFα and LTα secretion when T-cell stimulators are used. These findings will contribute to define disease heterogeneity in IBD and may be of relevance for understanding the pathogenesis of autoimmune diseases.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-3083.1996.d01-65.x
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