Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 7 de 7
Filter
Add more filters










Database
Language
Publication year range
1.
Neurology ; 65(7): 1083-9, 2005 Oct 11.
Article in English | MEDLINE | ID: mdl-16217063

ABSTRACT

OBJECTIVE: To evaluate clinical, genetic, and electrophysiologic features of patients with Andersen-Tawil syndrome (ATS) in the United Kingdom. METHODS: Clinical and neurophysiologic evaluation was conducted of 11 families suspected to have ATS. Molecular genetic analysis of each proband was performed by direct DNA sequencing of the entire coding region of KCNJ2. Control samples were screened by direct DNA sequencing. The electrophysiologic consequences of several new mutations were studied in an oocyte expression system. RESULTS: All 11 ATS families harbored pathogenic mutations in KCNJ2 with six mutations not previously reported. Some unusual clinical features including renal tubular defect, CNS involvement, and dental and phonation abnormalities were observed. Five mutations (T75M, D78G, R82Q, L217P, and G300D) were expressed, all of which resulted in nonfunctional channels when expressed alone, and co-expression with wild-type (WT) KCNJ2 demonstrated a dominant negative effect. CONCLUSION: Six new disease-causing mutations in KCNJ2 were identified, one of which was in a PIP2 binding site. Molecular expression studies indicated that five of the mutations exerted a dominant negative effect on the wild-type allele. KCNJ2 mutations are an important cause of ATS in the UK.


Subject(s)
Andersen Syndrome/genetics , Genetic Predisposition to Disease/genetics , Mutation/genetics , Potassium Channels/genetics , Adolescent , Adult , Andersen Syndrome/physiopathology , Animals , Child , Child, Preschool , DNA Mutational Analysis , Female , Genetic Testing , Humans , Infant , Kidney Tubules/abnormalities , Male , Oocytes , Phenotype , Potassium Channels, Inwardly Rectifying/genetics , Tooth Abnormalities/genetics , Xenopus laevis
2.
Seizure ; 14(2): 81-4, 2005 Mar.
Article in English | MEDLINE | ID: mdl-15694559

ABSTRACT

Efficacy and tolerability of tiagabine was evaluated in patients with non-controlled partial seizures in a multicentre, open-label, parallel group study. Tiagabine was administered either two (b.i.d.) or three times daily (t.i.d.) as adjunctive therapy and titrated stepwise to a target of 40 mg/day during a 12-week, fixed-schedule titration period; this was followed by a 12-week flexible continuation period. The primary efficacy endpoint was the proportion of patients completing the fixed-schedule titration period. A total of 243 patients were randomised and received treatment, 123 to b.i.d. and 120 to t.i.d. dosing. Fewer patients in the b.i.d. (76 and 62%) than in the t.i.d. (87 and 72%) group completed the fixed-schedule titration period (OR: 0.562; 95% CI: 0.309-1.008; P=0.0532). The median percentage decrease in all types of seizure (excluding status epilepticus) during the fixed schedule titration period was 33.4% for the b.i.d. and 23.8% for the t.i.d. groups (P=0.9634; Van Elteren's test). The proportion of responders was similar for the b.i.d. and t.i.d. groups. There were no significant differences between dosage regimens in the change in median seizure rates from baseline. Adverse events were more frequent during the titration than the continuation period. Most events were mild and related to the central nervous system. Although their incidence was similar between treatment groups, severity was more frequent in the b.i.d. group. Our results suggest that during titration tiagabine is better tolerated with t.i.d. dosing, but during long-term maintenance, a t.i.d. schedule is as effective and well tolerated as b.i.d.


Subject(s)
Anticonvulsants/pharmacokinetics , Anticonvulsants/therapeutic use , Drug Resistance , Epilepsy/drug therapy , Nipecotic Acids/therapeutic use , Anticonvulsants/adverse effects , Child , Dose-Response Relationship, Drug , Drug Administration Schedule , Drug Tolerance , Female , Humans , Male , Nipecotic Acids/administration & dosage , Nipecotic Acids/adverse effects , Tiagabine
3.
Br J Hosp Med ; 57(6): 277-80, 1997.
Article in English | MEDLINE | ID: mdl-9196574

ABSTRACT

Treatments that reduce disease activity in multiple sclerosis are now available, but it is not known how these agents will modify the development of disability in the long term. Published trials of the use of interferon beta failed to detect any clinically relevant reduction in accumulation of disability during the study period. Should patients therefore be prescribed these compounds?


Subject(s)
Interferon-beta/therapeutic use , Multiple Sclerosis/therapy , Antibody Formation , Clinical Trials as Topic , Dose-Response Relationship, Drug , Evidence-Based Medicine , Humans , Interferon-beta/adverse effects , Multiple Sclerosis/immunology , Treatment Outcome
SELECTION OF CITATIONS
SEARCH DETAIL
...