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Biomedical subjects

N E Gilhus

Publications and source records attributed to N E Gilhus.

At least 19 recordsLinked to original sources
PubMed2000

Autoantibodies in thymoma-associated myasthenia gravis with myositis or neuromyotonia.

BACKGROUND: About 50% of patients with thymoma have paraneoplastic myasthenia gravis (MG). Myositis and myocarditis or neuromyotonia (NMT) will also develop in some. Patients with thymoma-associated MG produce autoantibodies to a variety of neuromuscular antigens, particularly acetylcholine receptor (AChR), titin, skeletal muscle calcium release channel (ryanodine receptor [RyR]), and voltage-gated potassium channels (VGKC). OBJECTIVE: To examine whether neuromuscular autoantibodies in patients with thymoma correlate with specific clinical syndromes. METHODS: Serum and plasma samples from 19 patients with thymoma-associated MG, of whom 5 had myositis and 6 had NMT, underwent testing for antibodies to AChR, titin, RyR, and VGKC. RESULTS: Antibodies to AChR and titin were found in 19 and 17 patients, respectively. Antibodies to RyR correlated with the presence of myositis (P = .03); they were found in all 5 patients with myositis and in only 1 patient with NMT, but also in 4 of 8 patients with neither disease. Antibodies to VGKC were found in 4 patients with NMT, 1 of 3 patients undergoing testing for myositis, and 2 of 7 patients undergoing testing with neither comorbidity. Presence of RyR antibodies correlated with high levels of titin antibodies. CONCLUSIONS: The results appear to distinguish partially between 3 groups of patients with thymoma-associated MG: the first with RyR antibodies and myositis or myocarditis, the second with NMT without RyR antibodies, and the third without RyR antibodies, myositis, or NMT. Differences in the thymoma may underlie these pathologic associations.

Adult↗
PubMed1999

[Specialized positions, time allocation and clinical research at the Haukeland hospital].

An aim for Norwegian health care is to improve clinical medical research. Special positions for junior doctors are designated for research, quality control projects or subspecialization. In addition, four hours per week for all doctors at Haukeland University Hospital have recently been allocated to theoretical study. A questionnaire was sent to the heads of all 27 departments of Haukeland University Hospital to survey the use of these opportunities for medical research. There were 27 junior doctor positions for clinical research in 12 different departments, constituting 4% of all positions for doctors at the hospital. 15 departments, including several large ones, did not have any junior doctor positions for clinical research. For 15 of the 27 positions, approximately 50% of the working time was used for research with the goal of publishing in international referee-based journals. Four positions were used for clinical subspecialization, and eight positions were used entirely for routine clinical work. 14 department heads would give high priority to a new position for clinical research. Only 11 department heads claimed that the hours scheduled for theoretical work had improved research to some degree. There was general agreement that other aspects of department organisation was more important for promotion of research. Clinical research positions for junior doctors should be used for research, but even in an ambitious university hospital they are not fully used for such work. Most of the department heads have a clear ambition to improve the conditions for research in their departments.

Education, Medical, Continuing↗
PubMed1999

TNFA and TNFB polymorphisms in myasthenia gravis.

BACKGROUND: Tumor necrosis factor (TNF) alpha and TNF-beta are proinflammatory cytokines thought to be involved in the pathogenesis of myasthenia gravis (MG). OBJECTIVE: To examine whether TNF polymorphisms are associated with MG, MG subgroups, and the presence of titin and ryanodine-receptor antibodies. PATIENTS AND METHODS: We did genotyping on 30 patients with MG and 92 healthy blood donors for 2 biallelic TNFA polymorphisms (G to A at positions -238 and -308) and 1 TNFB polymorphism (NcoI digestive site) using methods based on the polymerase chain reaction. RESULTS: Patients with thymoma were typically homozygous for both the TNFA*T1 and the TNFB*2 alleles, but patients having an early onset of MG without thymoma were carriers of the TNFA*T2 and TNFB*1 alleles. Patients without thymoma who had the titin antibody had the same high frequency of TNFA*T1 and TNFB*2 as patients with thymoma, whereas patients without the titin antibody carried the same allele, TNFA*T2 and TNFB*1, regardless of age and thymic disease. No association was found with acetylcholine-receptor levels or disease severity for any of the TNFA or TNFB polymorphisms. CONCLUSION: Patients having MG, including those with thymoma, who have the titin antibody are most often homozygous for the TNFA*T1 and TNFB*2 alleles, whereas the presence of the TNFA*T2 and TNFB*1 alleles correlates with early-onset MG and the absence of titin antibodies.

Adult↗
PubMed1999

A new way of building a database of EEG findings.

Whereas computer-based electroencephalography (EEG) is widely applied, the EEG interpretations are usually not stored in a way that favours exploitation of modern computer technology. This paper reports an EEG description system facilitating categorization of EEG data in a computerized database. The system interactively communicates with the digital EEG system and also with the general patient administrative system. The main new quality of this system is the methods for data input and automatic data retrieval from several systems, rather than the establishment of a database of EEG data itself. The EEGs are visually analysed and categorized. Manually marked EEG events are automatically transferred to the database and such events as well as defined electrode positions within these epochs are directly linked to their corresponding descriptions. The database is updated without demand for filling in the events in the database in a second operation. Thereby, the EEG interpreter builds the database while analysing the EEG. This system provides an improved accessibility of EEG data for clinical, normative, educational and scientific use.

Brain↗
PubMed1998

[Wound botulism in heroin addiction].

Botulism is a rare disease which usually is caused by preformed botulinum toxin in food. However, this article describes a case of wound botulism in a 29-year-old male heroin addict who developed progressive diplopia, dysphagia and proximal weakness of skeletal limb muscles. He needed mechanical ventilation for two weeks. The clinical diagnosis of botulism was supported by neurophysiological tests. Assays for detection of botulinum toxin and Clostridium botulinum were negative. The patient had not eaten any contaminated food the last two weeks before symptoms appeared, but he had multiple contaminated skin wounds. After treatment with botulinum antitoxins and antibiotics he gradually recovered, and six weeks later he was discharged from hospital in good condition. To the best of our knowledge this is the first case of wound botulism reported in Norway.

Adult↗
PubMed1998

[The annual neurological conferences 1990-97--extensive scientific presentation for Norwegian neurologists].

324 free oral presentations were put forward during the Norwegian annual neurology conferences in 1990-1997. The lead authors of 216 presentations (67%) were employed at university hospitals; 108 authors were in employment at other hospitals or institutions. 159 lead authors (49%) were specializing in neurology and these candidates became increasingly active as presenters during the period in question. International collaboration occurred in 27 of the presentations (8%), nine of the presenters working with colleagues in the USA and seven with colleagues in Sweden. The presentations were classified as either mainly clinical, with 275 presentations (85%), or mainly basal science, with 31 presentations. In the remaining 18 presentations administrative or historic-literary topics were discussed. The disorders most frequently dealt with were epilepsy (88 presentations), cerebrovascular disorders (52 presentations), and autoimmune disorders (47 presentations). There was an increasing trend towards the latter two topics during the conference period. In conclusion, this survey shows neurology to be an expansive specialty with a focus on active development and research.

Humans↗
PubMed1998

Myasthenia gravis sera containing antiryanodine receptor antibodies inhibit binding of [3H]-ryanodine to sarcoplasmic reticulum.

Myasthenia gravis (MG) patients with thymoma often have antibodies against the calcium-release channel of the sarcoplasmic reticulum (SR) in striated muscle, the ryanodine receptor (RyR). RyR function can be tested in vitro by measuring the degree of [3H]-ryanodine binding to SR. In this study, sera from 9 out of 14 MG patients containing RyR antibodies inhibited [3H]-ryanodine binding to SR membranes from rat skeletal muscle. The 9 patients with antibodies inhibiting ryanodine binding had more severe MG than those with noninhibiting antibodies (P = 0.006). Sera from MG patients with acetylcholine receptor and titin muscle antibodies but no antibodies against RyR and blood-donor sera did not have an inhibiting effect in the [3H]-ryanodine binding assay. The results show that RyR antibodies in MG patients have high affinity for the RyR, and that the binding of antibodies probably affects calcium release from SR by locking the RyR ion channel in a closed position.

Animals↗
PubMed1998

Striational autoantibodies in myasthenia gravis patients recognize I-band titin epitopes.

Myasthenia gravis (MG) patients develop autoantibodies primarily against the acetylcholine receptor in the motor endplate, but also against intracellular striated muscle proteins, notably titin, the giant elastic protein of the myofibrillar cytoskeleton. Titin antibodies have previously been shown to be directed against a single epitope on the molecule, located at the A-band/I-band junction and referred to as the main immunogenic region (MIR) of titin. By using immunofluorescence microscopy on stretched single myofibrils, we now report that approximately 40% of the sera from 18 MG/thymoma patients and 8 late-onset MG patients with thymus atrophy contain antibodies that bind to a more central I-band titin region. This region consists of homologous immunoglobulin domains and is known to be differentially spliced dependent on muscle type. All patients with I-band titin antibodies also had antibodies against the MIR. Although a statistically significant correlation between the occurrence of I-band titin antibodies and MG severity was not apparent, the results could hint at an initial immunoreactivity to titin's MIR, followed by reactivity along the titin molecule in the course of the disease.

Adult↗
PubMed1998

FcgammaRIIA and FcgammaRIIIB polymorphisms in myasthenia gravis.

The Fcgamma receptors, FcgammaRIIA and FcgammaRIIIB contain polymorphisms with different capacity for IgG binding and phagocytosis. Thirty myasthenia gravis (MG) patients and 49 healthy controls were genotyped for the FcgammaRIIA and FcgammaRIIIB polymorphisms using polymerase chain reaction. The frequency of the FcgammaRIIA-H/H genotype was increased in thymoma MG patients compared to other MG patients (P = 0.05) and controls (P = 0.02). The distribution of FcgammaRIIIB alleles in MG patients did not differ from the controls, but MG patients with the NA1/NA1 genotype had the most severe MG (P = 0.01). Levels of AChR-antibodies and frequency of titin or ryanodine receptor antibodies were not associated with the FcgammaRIIA or FcgammaRIIIB genotypes. The results suggest different pathogenetic mechanisms in paraneoplastic and non-paraneoplastic autoimmune MG.

Age of Onset↗
PubMed1998

Cell-mediated immune response against titin in myasthenia gravis: evidence for the involvement of Th1 and Th2 cells.

Myasthenia gravis (MG) patients may have circulating autoantibodies against titin. In this study, we have stimulated T cells from MG patients with a recombinant polypeptide containing the main immunogenic region of titin, MGT-30 (myasthenia gravis titin-30 kDa). In an ELISpot assay, MGT-30 reactive interferon (IFN)-gamma secreting cells (Th1 cells) were detected in six of 10 titin antibody positive MG patients. Such cells were not detected in any of the five titin antibody negative MG patients or in the seven blood donors. In three patients, the stimulated number of cells decreased when total remission of MG symptoms was achieved after thymectomy or following a period of intensive immunosuppressive medication. We detected MGT-30 interleukin (IL)-4 secreting cells (Th2 cells) in two of five titin antibody positive MG patients, but not in the two titin antibody negative patients or the five blood donors examined. We conclude that titin antibody positive MG patients have a combined Th1/Th2 cell mediated immunity against the muscle protein titin.

Adjuvants, Immunologic↗
PubMed1997

[Diagnosis of thymoma and thymic atrophy in patients with myasthenia gravis].

We have compared clinical, immunological and radiological data in 20 patients with myasthenia gravis and thymoma and in 21 patients with myasthenia gravis and thymic atrophy. The median age at onset was 54 years in the thymoma group and 63 years in the thymic atrophy group (p = 0.04). The severity of the disease was similar in the two groups, and there was no significant difference in the concentration of acetylcholine receptor antibodies. CA antibodies were demonstrated in 17/20 thymoma patients and in 6/21 with thymic atrophy, while 19/20 thymoma patients had antibodies to titin, compared with 9/21 among those with thymic atrophy. The diagnosis and treatment of patients with myasthenia gravis is based upon an evaluation of clinical, immunological and radiological data.

Adult↗
PubMed1997

[The post-poliomyelitis syndrome--a real complication. A poliomyelitis material from the Haukeland hospital].

Over a four-year period, all in-patients at our department with the diagnosis of polio-sequelae were clinically examined for development of new neuromuscular deficit. 19 out of 125 patients (15%) had developed a postpolio syndrome. All 19 had acquired additional functional deficit and 17 new, localized pareses. Five patients had developed polio-related hypoventilation. The mean time from acute poliomyelitis to debut of the post-polio syndrome was 39 years. The post-polio syndrome occurred in patients with severe pareses in the acute stage, but was not related to age, sex or specific epidemic. Most of the 106 other patients had similar subjective complaints but did not have any clinical signs indicating new neuromuscular deficit. 67 of these patients had tendinitis and/or myalgia and 83 had chronic pain. Whereas many patients have progressive symptoms many years after poliomyelitis, only a minority develop the post-polio syndrome.

Adult↗
PubMed1997

Titin transcripts in thymomas.

More than 90% of myasthenia gravis (MG) patients with a thymoma have antibodies against titin. We have identified titin mRNA transcripts in thymomas by RT-PCR and Southern blotting. The transcripts cover the main immunogenic region (MIR) and a central I-band epitope reactive with some MG patients' antibodies. The presence of the central I-band epitope was confirmed by immunohistochemistry as a titin antibody reactive with this part of titin, stained thymoma epithelial cells and a thymoma extract in Western blots. Our findings suggest that the initiation of paraneoplastic titin reactivity is correlated with the expression of titin sequences within the thymoma.

Adolescent↗
PubMed1997

Poliomyelitis: long-time consequences for social life.

In a study of 102 consecutive patients hospitalized for previous poliomyelitis, we found that 70 patients had continued education after elementary school and 18 were academics. This is a higher proportion than in the general Norwegian population. All 14 patients with paraparesis had continued education after elementary school, while as many as 12 of 18 patients with a university degree had widespread pareses in the acute phase. Of the patients 46 worked or had worked full-time up to 60 years of age. Only 29 patients were receiving a disabled pension. Another 9 patients had neither been employed nor received any pension, all housewives. Nine of 14 patients with paraparesis were working full-time, only 2 received disabled pension. Among the 35 patients with persisting widespread pareses, 11 were still in full-time work and 7 were working part-time. The employment rate among the patients in this study was nearly identical to the age-correlated general employment rate in Norway. Our conclusion is that polio patients are doing well in society; they have taken education, are working, and are generally self-supported. The degree of pareses does not seem to have been the most determining factor for their educational and professional activity.

Adult↗
PubMed1997

Autoimmunity to ryanodine receptor and titin in myasthenia gravis is associated with GM allotypes.

Myasthenia gravis (MG) is mediated by autoantibodies against the acetylcholine receptor at the muscle endplate. Some MG patients have in addition antibodies (Ab) to the skeletal muscle proteins ryanodine receptor (RyR) and titin. We have examined GM and KM allotypes, RyR and titin Ab in 44 MG patients (37 thymoma patients and 7 non-thymoma, late-onset patients) and 292 non-MG controls to see if GM/KM allotypes associate with differences in autoantibody production. All patients had titin Ab, and 15 thymoma patients had also RyR Ab. The phenotype GM 1, 2, 3 23 5, 21 was significantly increased in the patients with titin Ab compared with the non-MG controls (chi2 = 4.93, p < 0.05). Thymoma patients with RyR Ab had a higher frequency of the GM 3 23 5 phenotype compared with RyR Ab negative patients and controls (chi2 = 7.1, p < 0.05). KM allotypes did not differ between RyR Ab positive or titin Ab positive patients and controls. GM phenotypes may thus be associated with an autoimmune response against the muscle proteins titin and RyR in MG patients.

Adult↗