Biomedical subjects

N E Gilhus

Publications and source records attributed to N E Gilhus.

At least 73 records · Page 4Linked to original sources

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↗

PubMed1996

[Neurology--may recruitment cover the demand?].

New therapeutic possibilities have recently been introduced for many neurological disorders. The demand for specialists is, accordingly, increasing. To investigate the present status, and to give some ideas as to the future recruitment of neurologists, a questionnaire study has been performed among all neurological departments and their residents. In addition, figures from The Norwegian Medical Association have been analyzed. In October 1995, Norway had 209 neurologists, of whom 165 were of working age (67 years or younger). Of a total of 115 positions for neurologists in regional and county hospitals, 16 were vacant. The posts in hospitals with no neurological beds were most frequently vacant. An average of 7-8 new neurologists are now educated annually. This is slightly higher than the annual number of retirements, resulting in a net increase in the number of neurologists. However, this positive trend will be reversed as the retirement rate increases around year 2010. The residents were generally enthusiastic about working with neurological patients and wished to complete their appointments. The number of neurologists in Norway is too low compared with international standards. In order to obtain a satisfactory neurological service the recruitment rate needs to be increased.

Adult↗

PubMed1995

Antigen presentation by thymoma epithelial cells from myasthenia gravis patients to potentially pathogenic T cells.

Thymomas associate strongly with myasthenia gravis (MG). We now show that cultured thymoma epithelial cells can present synthetic acetylcholine receptor (AChR) peptides to HLA-sharing responder T cell lines/clones nearly as efficiently as blood mononuclear cells. Responses depended strictly on the specific antigen added. Processing of longer recombinant AChR polypeptides was clearly less efficient than by blood mononuclear cells, and was selectively abolished by preculture with chloroquine. The T cell responses depended on the presence of LFA-3 on the thymoma cells. This study demonstrates that thymoma epithelial cells have the capacity to stimulate T cells and perhaps, therefore, to autosensitize against AChR in vivo.

Antigen-Presenting Cells↗

PubMed1995

Thymomas express epitopes shared by the ryanodine receptor.

Myasthenia gravis (MG) patients with thymoma have antibodies against ryanodine receptor (RyR) of skeletal and heart muscle. In this study, thymomas were examined for reactivity with a panel of polyclonal rabbit antibodies against various short peptides of RyR. An antibody against peptide C2 in the transmembrane region of RyR stained thymoma epithelial cells in cryosections of 17/23 thymomas, and detected a 40-kDa peptide in Western blotting of a thymoma membrane fraction. The other RyR antibodies did not react with thymoma tissue. The anti-C2 RyR antibody did not react with normal thymus, tonsil or carcinoma of colon. The results strongly indicate that epithelial thymoma cells express an epitope shared by the transmembrane region of skeletal and cardiac muscle RyR.

Amino Acid Sequence↗

PubMed1995

Oncogene proteins and proliferation antigens in thymomas: increased expression of epidermal growth factor receptor and Ki67 antigen.

AIMS: To examine thymomas for proteins encoded by oncogenes and to determine whether their presence correlates with tumour growth and associated myasthenia gravis. METHODS: Sections of 24 thymomas were incubated with anti-EGF receptor (EGF-R), anti-Ki67 antigen, anti-p53, and anti-bcl-2 antibodies, and then stained using the alkaline phosphatase/anti-alkaline phosphatase (APAAP) technique. Cell suspensions and epithelial cell cultures from some of the tumours were also studied. RESULTS: Whereas EGF-R expression was not detected in any of the controls (but only in a 20 week old fetus), it was detected in neoplastic epithelial cells of all thymomas, and was most strongly expressed in metastases and in samples from donors with severe myasthenia gravis. Ki67 labelling was also increased, especially in the larger thymomas. Epithelial expression of both of these markers was confirmed in fresh cell suspensions and monolayer cultures from the five available cases. In contrast, p53 and bcl-2 were not detected in the neoplastic cells, but bcl-2 was present in the intermingling thymocytes. CONCLUSIONS: Neoplastic thymoma cells express EGF-R and Ki67, but there is no concomitant increase in the expression of p53 and bcl-2 proteins. Increased EGF-R expression may result in increased proliferation of neoplastic cells and also in myasthenia gravis. Measurement of EGF-R concentrations may be of prognostic value. The bcl-2 staining pattern in T lymphocytes illustrates the broad spectrum of maturational stages in thymoma lymphocytes.

Adolescent↗

PubMed1995

Titin antibodies in patients with late onset myasthenia gravis: clinical correlations.

We have tested sera from 21 thymectomized patients with onset of MG after 40 years of age and without thymoma for antibodies against titin, using ELISA with the titin peptide MGT-30. Titin is a myofibrillar protein unique to striated muscle and important for the elastic recoil of muscle cells. Titin antibodies were detected in 9 of the 21 sera. MG symptoms as assessed by a 6 point disability score (0-5) were significantly more severe in the titin antibody positive patients both at peak of illness; 3.7 vs. 3.1 (p < 0.02) and at latest follow up; 2.1 vs. 0.8 (p < 0.01). All titin antibody positive patients were on immunosuppressive drug treatment at least follow-up, whereas only 3 of 12 patients without titin antibodies used immunosuppressive drugs. The presence of circulating titin antibodies in late-onset non-thymoma MG patients indicates a more severe disease.

Age Factors↗

PubMed1994

Intranasal sumatriptan for the acute treatment of migraine. International Intranasal Sumatriptan Study Group.

Two double-blind, placebo-controlled, randomised, multicentre, multinational, parallel-group studies were carried out to identify the optimum dose of intranasal sumatriptan for the acute treatment of migraine. Study medication was taken as a single dose through one nostril in the first study, and as a divided dose through two nostrils in the second study. Totals of 245 and 210 patients with a history of migraine were recruited into the one- and two-nostril studies, respectively. In both studies, headache severity had significantly improved at 120 min after doses of 10-40 mg sumatriptan compared to placebo (P < 0.05) and the greatest efficacy rates were obtained with 20 mg sumatriptan. With 20 mg sumatriptan 78% and 74% of patients experienced headache relief in one- and two-nostril studies respectively. Sumatriptan was generally well tolerated, the most frequently reported event being taste disturbance. The results of the two studies are similar and indicate that administering sumatriptan as a divided dose via two nostrils confers no significant advantage over single-nostril administration.

Acute Disease↗

PubMed1994

Ryanodine receptor antibodies related to severity of thymoma associated myasthenia gravis.

Ryanodine receptor (RyR) antibodies are detected in about 50% of patients with myasthenia gravis who have a thymoma. The RyR is a calcium release channel involved in the mechanism of excitation-contraction coupling in striated muscle. In this study the severity of myasthenia gravis assessed by a five point disability score was compared between 12 patients with myasthenia gravis, a thymoma, and RyR antibodies and 10 patients with myasthenia gravis and a thymoma but without such antibodies. Symptoms of myasthenia gravis were significantly more severe in patients with RyR antibodies. The mean (SD) disability scores were 3.7(0.5) in patients with antibodies and 2.7 (0.9) in those without at peak of illness, (p = 0.01) and 3.4(1.4) v 1.6(0.7) at the end of an average observation period of five years (p = 0.002). The number of deaths due to myasthenia gravis was five of 12 RyR antibody positive patients, and none of 10 RyR antibody negative patients (p = 0.04). RyR antibody levels correlated positively with severity of myasthenia gravis. The presence of circulating RyR antibodies seems to be associated with a severe form of thymoma associated myasthenia gravis.

Adult↗

PubMed1994

Subcutaneous sumatriptan during the migraine aura. Sumatriptan Aura Study Group.

This double-blind, placebo-controlled, multicenter, parallel-group study assessed whether subcutaneous sumatriptan administered during the migraine aura would prolong or modify the aura and prevent or delay development of the headache. One hundred seventy-one patients (88 receiving 6 mg sumatriptan, 83 receiving placebo) treated a single attack of migraine with typical aura at home, by self-injection. The median duration of aura following the first injection was 25 minutes for the sumatriptan group and 30 minutes for the placebo group (NS). The aura symptom profile was similar for the two treatment groups. The proportion of patients who developed a moderate or severe headache within 6 hours after dose administration was similar in the two groups--68% among those receiving sumatriptan and 75% among those receiving placebo (NS). Sumatriptan given during the aura did not prolong or alter the nature of the migraine aura and did not prevent or significantly delay headache development.

Adult↗

PubMed1994

Anti-cardiac ryanodine receptor antibodies in thymoma-associated myasthenia gravis.

Sera from myasthenia gravis (MG) patients with thymoma were examined in Western blot for the presence of antibodies to proteins in the sarcoplasmic reticulum (SR) of cardiac muscle. Fourteen of 30 MG thymoma sera had IgG antibodies to a protein with the same electrophoretic mobility as cardiac muscle ryanodine receptor (RyR). Anti-cardiac RyR antibodies were not detected in any of the 45 sera from MG patients without thymoma. The same 14 MG thymoma sera, but none of the others, bound to RyR from skeletal muscle as well. Neutralization experiments showed that the anti-RyR antibodies in MG patient cross-reacted with cardiac and skeletal muscle RyR. Since skeletal and cardiac muscle RyRs are antigenically different, our findings may indicate that autoantibodies to RyR in MG originate by sensitization to a peptide shared by cardiac and skeletal muscle RyR, rather than to the complete native RyR.

Autoantibodies↗

PubMed1993

IgG subclass distribution of ryanodine receptor autoantibodies in patients with myasthenia gravis and thymoma.

Patients with myasthenia gravis (MG) and thymoma often have autoantibodies to the ryanodine receptor (RyR), a ligand-gated Ca(2+)-release channel in the sarcoplasmic reticulum of striated muscle. Using an ELISA, we studied the Ig isotype and IgG subclass distribution of RyR autoantibodies in sera from 30 MG patients with thymoma. RyR IgG antibodies were detected in 16/30 sera. 14/30 sera had IgG1 RyR antibodies, and 15/30 sera had IgG3 RyR antibodies. All sera with IgG1 RyR antibodies also contained IgG3 antibodies. A small number of sera had low amounts of IgG2, IgG4, IgA or IgM RyR antibodies. The RyR autoantibodies are therefore mainly expressed in the IgG1 and IgG3 subclasses. The RyR autoantibodies may be of pathogenic significance by interfering with the mechanism of excitation-contraction coupling in striated muscle.

Autoantibodies↗

PubMed1993

Titin antibodies in myasthenia gravis: identification of a major immunogenic region of titin.

Approximately 15% of patients with myasthenia gravis (MG) have thymus neoplasia. These MG with thymoma (MGT) patients show autoantibodies to striated muscle as well as autoantibodies to acetylcholine receptor. To characterize these thymoma-associated muscle antigens, we cloned a number of immunopositive cDNAs by immunoscreening muscle cDNA libraries with sera from MGT patients. Analysis of the isolated cDNAs show that all share a common sequence encoding a distinct region of the titin gene. We expressed this main immunogenic region (MIR) of titin in Escherichia coli, and determined autoantibody serum titers directed against the obtained recombinant antigen in a variety of patients. We could detect titin MIR autoantibodies in 97% of sera from MGT patients but not in control sera from healthy blood donors. Therefore, expressed titin from the MIR of the molecule is a sensitive marker antigen for evaluating the presence of thymoma in MG.

Amino Acid Sequence↗

PubMed1992

Left ventricular function in myasthenia gravis.

Myasthenia gravis is an autoimmune disorder with autoantibodies to acetylcholine receptors of skeletal muscle. Left ventricular diastolic function was studied with M-mode and Doppler echocardiography in 25 patients with myasthenia and in a group of age- and heart rate-matched control subjects. In the patients, diastolic peak filling rate was reduced by 37%, and Doppler peak early filling velocity (E) was reduced by 12% compared with the control subjects (2.7 +/- 0.7 vs 4.2 +/- 1.0 s-1, and 76 +/- 8 vs 85 +/- 15 cm/s, respectively; p less than 0.05). Peak atrial filling velocity (A) was increased by 38% (68 +/- 17 vs 48 +/- 9 cm/s; p less than 0.01), and consequently the E:A ratio in the group of patients was reduced by 33% (1.22 +/- 0.40 vs 1.81 +/- 0.33; p less than 0.001). End-diastolic dimension was 5.0 +/- 0.5 cm in both groups, heart rate was 70 +/- 12 vs 68 +/- 16 beats/min (p = not significant [NS]), M-mode ejection fraction was 76 +/- 8 vs 79 +/- 5% (p = NS), M-mode peak ejection rate was -1.9 +/- 0.4 vs -2.1 +/- 0.3 s-1 (p = NS), and peak aortic outflow velocity was 109 +/- 18 vs 98 +/- 13 cm/s (p = NS). Twenty-three patients and 15 control subjects were studied before and after intake of the acetylcholine-esterase inhibitor pyridostigmine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Ryanodine receptor autoantibodies in myasthenia gravis patients with a thymoma.

Sera from patients with myasthenia gravis were examined by Western blot for the presence of antibodies to proteins of the sarcoplasmic reticulum from rabbit skeletal muscle. Fourteen of 30 patients with myasthenia gravis and a thymoma had IgG autoantibodies to the calcium release channel of the sarcoplasmic reticulum (the ryanodine receptor), which plays a crucial role in the mechanism of excitation-contraction coupling in striated muscle. Ryanodine receptor autoantibodies were not detected in any of the 45 sera from patients with myasthenia gravis without a thymoma. Ryanodine receptor autoantibodies may have pathogenetic relevance in thymoma-associated myasthenia gravis.

Autoantibodies↗

PubMed1992

Myasthenia gravis patients with a thymoma have antibodies against a high molecular weight protein in sarcoplasmic reticulum.

Our purpose was to investigate whether components of the sarcoplasmic reticulum (SR) are relevant antigens in myasthenia gravis (MG). Using enzyme-linked immunosorbent assay (ELISA), 75 MG sera and 120 control sera were examined for IgG antibodies against SR prepared from rabbit skeletal muscle. 16/30 thymoma MG patients had IgG antibodies that reacted with SR. 1/30 MG patients with thymic hyperplasia and 3/15 MG patients with thymic atrophy had SR antibodies in low concentrations. Control sera were negative. Using immunoblot, SR antibodies were detected in the thymoma group only. 14/30 sera from thymoma patients reacted with a protein of 320 kDa relative molecular weight. The only reported SR protein with similar electrophoretic mobility is the subunit of the spanning protein which links junctional SR to sarcolemma and functions as a calcium-release channel.

Adult↗