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- Braathen, Gunnar
(författare)
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One-year versus three-year treatment of children with uncomplicated epilepsy : a prospective study
- 1997
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The main purpose of this prospective study was to investigate whether one-year treatment was equally efficient, regarding the remission rate, as three-year treatment of children with uncomplicated epilepsy. Our aim was also to find any prognostic factors related to the remission rate which would enable us to predict the outcome for the individual child. The duration of treatment was randomized to one year (Group 1) or three years (Group 11) before initiation of drug treatment in 234 children with newly diagnosed epilepsy, aged 2-16 years, with no neurological disabilities. Seizures and epileptic syndromes were classified according to the well-established ILAE system. Partial epilepsies were found in 137 children (59%), 68 children (29%) had generalized epilepsies and in 29 children (12%) it was uncertain whether the epilepsy was partial or generalized. Six main diagnostic groups were identified: simple parbal seizures (SPS 8%), complex partial seizures (CPS, 23%), benign partial epilepsy with centrotemporal (rolandic) spikes (BECT, 9%), generalized tonic-clonic seizures as the only ictal manifestation in children with rolandic spikes (2°GTCS-rol, 13%), absence epilepsy (AE, 12%) and primarily generalized tonic-clonic seizures (1°GTCS, 19%). The drug therapy could be completed in 161 children (78%), according to the planned schedule and the criterion of freedom from seizures during the last six months of treatment. The children were followed up for 2-10 years after the end of treatment. Relapses occurred in 60 children (37%). The relapse rate was 47% in Group I and 29% in Group ll (p <0.05). The relapse rate in children with CPS was significantly higher in Group I than in Group 11 (p <0.05). If children with CPS were not considered, the difference in outcome between the groups was not statistically significant. Children with BECT and SPS had the highest remission rates, children with CPS had the lowest and children with other types of epilepsy had remission rates in between. The EEG was recorded before treatment and at regular intervals during treatment. The existence of generalized irregular spike-and-wave (SW) activity after one year of treatment was associated with a poor outcome, as compared with children without these discharges (p <0.01). Persistent, regular 3-Hz SW after six months of treatment in children with absence epilepsy was also associated with a high relapse risk. Other epileptiform activities or background abnormalities did not influence the outcome. Prognostic factors of importance to the outcome were analysed by univariate and multiple regression analyses in 161 children from whom treatment was withdrawn. Factors found to have a positive influence on the outcome were (I) epilepsy type of BECT or SPS, (2) favourable age at seizure onset (younger than 10 years in children without rolandic spikes and older than 10 years in children with rolandic spikes) and (3) EEG recordings after one year of treatment free from irregular SW. These variables constituted a prognostic model with a simple scoring system, by which each child could receive a total score of 0-7. Children with a total score of 5-7 after one year of treatment had a relapse rate of 27% in Group I and 3% in Group 11. Discontinuation of the treatment could be recommended for these children at that time, while children with a total score of 0-2 had a high relapse risk (90% and 57% in Groups I and 11, respectively) and should continue treatment for at least two more years. In order to look for subtle, neurological impairments due to the drug therapy 19 children treated with carbamazepine (CBZ) were studied with a standardized test of fine and gross motor proficiency (Bruininks-Oseretsky test). The test was performed on two occasions on the same child, first during treatment and then after six months, when treatment had been completely withdrawn for three months. Significant improvements were found in response speed (p <.0.05), in all fine motor subtests together (p <0.01) and in the total test battery (p <0.05). A comparison group was tested on two occasions during treatment with CBZ. No improvements were found in this group. The results indicate side effects from CBZ treatment on motor proficiency and on fine motor functions in particular. The annual incidence of childhood epilepsy in the catchment area of Huddinge University Hospital was studied. The mean incidence during the period 1990-92 was 53 per 100,000 children, which was in accordance with the experience from similar studies. The results of this study showed that 65% of a population of children with epilepsy fulfilled the inclusion cnteria of the principal study.
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| 2. |
- Ghumra, Ashfaq, et al.
(författare)
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Structural requirements for the interaction of human IgM and IgA with the human Fc alpha/mu receptor
- 2009
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Ingår i: European Journal of Immunology. - : Wiley. - 1521-4141 .- 0014-2980. ; 39:4, s. 1147-1156
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Tidskriftsartikel (refereegranskat)abstract
- Here we unravel the structural features of human IgM and IgA that govern their interaction with the human Fc alpha/mu receptor (hFc alpha/mu R). Ligand polymerization status was crucial for the interaction, because hFc alpha/mu R binding did not occur with monomeric Ab of either class. hFc alpha/mu R bound IgM with an affinity in the nanomolar range, whereas the affinity for dimeric IgA (dIgA) was tenfold lower. Panels of mutant IgM and dIgA were used to identify regions critical for hFc alpha/mu R binding. IgM binding required contributions from both C mu 3 and C mu 4 Fc domains, whereas for dIgA, an exposed loop in the C alpha 3 domain was crucial. This loop, comprising residues Pro440-Phe443, lies at the Fc domain interface and has been implicated in the binding of host receptors Fc alpha RI and polymeric Ig receptor (pIgR), as well as IgA-binding proteins produced by certain pathogenic bacteria. Substitutions within the Pro440-Phe443 loop resulted in loss of hFc alpha/mu R binding. Furthermore, secretory component (SC, the extracellular portion of pIgR) and bacterial IgA-binding proteins were shown to inhibit the dIgA-hFc alpha/mu R interaction. Therefore, we have identified a motif in the IgA-Fc inter-domain region critical for hFc alpha/mu R interaction, and highlighted the multi-functional nature of a key site for protein-protein interaction at the IgA Fc domain interface.
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| 3. |
- Kilebrant, Sophie, et al.
(författare)
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WHOLE-BODY VIBRATION THERAPY IN CHILDREN WITH SEVERE MOTOR DISABILITIES
- 2015
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Ingår i: Journal of Rehabilitation Medicine. - : Foundation for Rehabilitation Information. - 1650-1977 .- 1651-2081. ; 47:3, s. 223-228
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To study the effect of whole-body vibration therapy on bone mass, bone turnover and body composition in severely disabled children. Methods: Nineteen non-ambulatory children aged 5.1-16.3 years (6 males, 13 females) with severe motor disabilities participated in an intervention programme with standing exercise on a self-controlled dynamic platform, which included whole-body vibration therapy (vibration, jump and rotation movements). Whole-body vibration therapy was performed at 40-42 Hz, with an oscillation amplitude of 0.2 mm, 5-15 min/treatment, twice/week for 6 months. Bone mass parameters and bone markers were measured at the study start, and after 6 and 12 months. Results: Whole-body vibration therapy was appreciated by the children. Total-body bone mineral density increased during the study period (p less than0.05). Z-scores for total-body bone mineral density ranged from -5.10 to -0.60 at study start and remained unchanged throughout. Approximately 50% of the subjects had increased levels of carboxy-terminal telopeptides of type I collagen and decreased levels of osteocalcin at the start. Body mass index did not change during the intervention period, but had increased by the 12-month follow-up (pless than 0.05). Conclusion: Whole-body vibration therapy appeared to be well tolerated by children with severe motor disabilities. Total-body bone mineral density increased after 6 months of whole-body vibration therapy. Higher carboxy-terminal telopeptides of type I collagen and lower osteocalcin values indicated that severely disabled children have a reduced capacity for bone acquisition.
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| 4. |
- Nyström, Anna-Maja, et al.
(författare)
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Noonan and cardio-facio-cutanenous syndromes : two clinically and genetically overlapping disorders
- 2008
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Ingår i: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 45:8, s. 500-506
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Tidskriftsartikel (refereegranskat)abstract
- Background: Noonan syndrome (NS) and cardio-facio-cutaneous syndrome (CFC) are related disorders associated with disrupted RAS/RAF/MEK/ERK signalling. NS, characterised by facial dysmorphism, congenital heart defects and short stature, is caused by mutations in the genes PTPN11, SOS1, KRAS and RAF1. CFC is distinguished from NS by the presence of ectodermal abnormalities and more severe mental retardation in addition to the NS phenotype. The genetic aetiology of CFC was recently assigned to four genes: BRAF, KRAS, MEK1 and MEK2. Methods: A comprehensive mutation analysis of BRAF, KRAS, MEK1, MEK2 and SOS1 in 31 unrelated patients without mutations in PTPN11 is presented. Results: Mutations were identified in seven patients with CFC (two in BRAF, one in KRAS, one in MEK1, two in MEK2 and one in SOS1). Two mutations were novel: MEK1 E203Q and MEK2 F57L. The SOS1 E433K mutation, identified in a patient diagnosed with CFC, has previously been reported in patients with NS. In one patient with NS, we also identified a mutation, BRAF K499E, that has previously been reported in patients with CFC. We thus suggest involvement of BRAF in the pathogenesis of NS also. Conclusions: Taken together, our results indicate that the molecular and clinical overlap between CFC and NS is more complex than previously suggested and that the syndromes might even represent allelic disorders. Furthermore, we suggest that the diagnosis should be refined to, for example, NS–PTPN11-associated or CFC–BRAF-associated syndromes after the genetic defect has been established, as this may affect the prognosis and treatment of the patients.
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