Biomedical subjects
Sten Fredrikson
Publications and source records attributed to Sten Fredrikson.
[A national curriculum in neurology for medical education].
The knowledge within medicine is growing rapidly. It has become more and more difficult to decide what knowledge that has to be taught to medical students during their University Medical Degree (MD) education and what has to be omitted from their study plans. As help for teachers and students, a core curriculum of the education defines what is of importance for all students. However, there is a risk of "curriculum overload" with too much information being put into a short time interval. To avoid this and to define what is really the "core" of a course, a national consensus decision may be useful. As an example of this approach, we here report a new joint Swedish core curriculum in neurology for medical students. Teachers responsible for neurological education at all six universities giving University MD education in Sweden have in January 2003 agreed upon the core curriculum that we present. It is our hope that this method can be useful also for other clinical specialities.
Concordance for disease course and age of onset in Scandinavian multiple sclerosis coaffected sib pairs.
BACKGROUND: Investigation of coaffected sib pairs is one method to determine the genetic influence on the clinical presentation of many complex diseases, such as multiple sclerosis (MS). Investigation of the clinical concordance in coaffected sib pairs may be a prerequisite to identify genes that modify the clinical outcome. The aim of this study was to investigate a possible genetic influence on selected demographic and clinical variables among familial Scandinavian MS cases. MATERIAL AND METHODS: We identified 136 Caucasian Scandinavian families with MS coaffected sib pairs from Denmark, Norway and Sweden. Cohen's kappa coefficient and the intraclass correlation coefficient were used to assess concordances in sib pairs. Furthermore, clinical features and HLA-DR2 carrier status were compared among the probands of sib pairs. RESULTS: We found significant concordance of the disease course (kappa = 0.28, P < 0.001) and adjusted age of onset (r = 0.23, P = 0.028). Among probands of sib pairs, HLA-DR2 carrier patients had a younger age of onset (P = 0.024). CONCLUSION: Analyses of Scandinavian coaffected sib pairs suggest that disease course and age of onset are partly under genetic control. Furthermore, HLA-DR2 in probands of sib pairs suggests importance for age of onset.
Prospective study of clinical epidemiology of Guillain-Barré syndrome in Harbin, China.
Clinical manifestations, outcomes, prognostic indicators, and clinico-epidemiological subgroups were described based on the information of 71 patients with Guillain-Barré syndrome (GBS), who were identified from a prospective survey in Harbin, China during a 1-year period from 1 October 1997 to 30 September 1998. GBS diagnoses of the patients were validated by senior neurologists and most patients were followed up for 6 months after onset. Antecedent events, mainly respiratory infections, were found in 55 (78%) patients during the month before onset. The clinical features, like motor weakness as initial symptoms (82%) and tendon areflexia or hyporeflexia (100%), are similar to those reported from other populations. However, the proportion (70%) of patients reaching to nadir less than 7 days after onset was rather high. Intravenous human immunoglobulin and/or plasmapheresis were used in 45% of the patients and steroids in 58%. At 6 months after onset, 82% of the patients could walk without aid, 46% of the patients had no any residual signs. Four (6%) patients died within 1 month due to respiratory failure. Three subgroups with different clinico-epidemiological characteristics were identified by using cluster analysis. In conclusion, GBS patients in Harbin, China were younger, had shorter time to nadir, frequently preceded by a respiratory infection, and often treated with steroids. Clinical and epidemiological differences of GBS might exist between various populations.
Interferon-beta treatment in patients with multiple sclerosis does not alter CYP2C19 or CYP2D6 activity.
AIMS: To determine CYP2C19 and CYP2D6 activity in patients with multiple sclerosis (MS) before and during interferon (IFN)-beta treatment. METHODS: CYP2C19 and CYP2D6 activities were assessed using the probe drugs mephenytoin and debrisoquine, respectively. Urinary mephenytoin (S/R) and debrisoquine (debrisoquine/hydroxy-debrisoquine) metabolic ratios (MR) were determined in 10 otherwise healthy Caucasian multiple sclerosis (MS) patients in the initial stage of the disease, prior to and 1 month after commencing treatment with IFN-beta (Avonex, Rebif or Betaferon). In addition, CYP2C19*2, CYP2C19*3, CYP2D6*3, CYP2D6*4, and CYP2D6*5 genotyping was performed. RESULTS: There was no significant difference in the (S)/(R) mephenytoin ratio (mean difference 0.04; 95% CI -0.03, 0.11) or the debrisoquine MR (mean difference 0.29; 95% CI -0.44, 1.02) before and during regular IFN-beta treatment in extensive metabolizers (EM) (P = 0.5 and P = 0.4 for the respective probe drugs; n = 9 subjects). There were also no differences between the different IFN-beta treatments (P = 0.6 for the (S)/(R) mephenytoin ratio and P = 0.7 for the debrisoquine MR; anova; n = 10). CONCLUSIONS: IFN-beta treatment did not affect the activity of CYP2C19 or CYP2D6. The results suggest that it is safe to administer CYP2C19 or CYP2D6 substrates, without dose adjustment, to patients treated with IFN-beta.
Early management of multiple sclerosis: report from the MS Forum 15th Modern Management Workshop.
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Report from the 55th Annual Meeting of the American Academy of Neurology (AAN).
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HHV-6 A- or B-specific P41 antigens do not reveal virus variant-specific IgG or IgM responses in human serum.
The etiology of multiple sclerosis (MS) remains unknown, but there are indications of a role of human herpesvirus 6 (HHV-6), especially variant A, in the pathogenesis. Higher serum antibody reactivity against an HHV-6 early protein, p41, has been found in MS cases than in controls. The antigen, however, was purified from infected cells with a monoclonal antibody also reactive with a protein (p38) likely to be of cellular origin. To avoid serological crossreactivity with the cellular protein, recombinant p41 proteins from HHV-6A strain GS and HHV-6B strain Z29 were expressed as glutathione-S-transferase fusion proteins (p41-GST), and used as antigens in an enzyme-linked immunosorbent assay (ELISA). p41 variant specific monoclonal antibodies reacted strongly with the respective recombinant proteins. Serum IgM and IgG reactivities with the recombinant p41 antigens were analysed in patients with manifest MS, patients with optic neuritis, patients with other neurological diseases, and in one group of healthy controls. All sera were HHV-6 IgG seropositive by immunofluorescence. The serum IgM or IgG reactivities against the recombinant p41 antigens did not differ significantly between the groups, and the reactivities against the variant A and B antigens were identical. In many samples, the reactivity was very low. The results indicate that p41 is not an optimal target for HHV-6 serology studies, and that the data obtained with the p41 antigen prepared from infected cells (possibly including also p38) should be interpreted with caution.
Distinct pattern of age-specific incidence of Guillain-Barré syndrome in Harbin, China.
We describe the age-and sex-specific incidence of Guillain-Barré syndrome (GBS) in Harbin, China, based on the information from a prospective survey among a well-defined large population during one year. A network of physicians reported incident patients with a GBS diagnosis from a general population of 5.4 million inhabitants in Harbin, China, during the period from 1 October 1997 to 30 September 1998. Each reported patient was examined by senior neurologists and the GBS diagnosis was validated according to standard diagnostic criteria. All GBS patients were followed-up for six months after onset. Admission registers at all hospitals in Harbin were also checked afterwards for screening patients with a GBS diagnosis who might have been missed. During the study period, 79 patients with a GBS diagnosis were reported. After validation, the GBS diagnosis was confirmed in 70 patients. Another GBS patient was found through the screening of admission registers at hospitals. Among them, 36 GBS patients were residents in Harbin and the other 35 patients were from geographical areas out of Harbin. The GBS incidence, age-adjusted to the European standard population, was 0.66 (95% CI 0.46-0.91) per 100,000 person-years, with a male to female ratio of 1.4. The highest GBS incidence was found in the youngest age-group and the incidence among the elderly was remarkably lower than those reported from other populations in Western countries. Possible explanations for the distinct pattern of age-specific incidence of GBS are discussed. Further studies are needed.