Subjective evaluation of the effect of treatment of excessive daytime sleepiness (EDS) with dexamphetamine and of cataplexy with clomipramine was made in 124 subjects with the narcoleptic syndrome. Drug effects were evaluated by self-report of the propensity to EDS and cataplexy as determined by the Epworth Sleepiness Scale and a rating scale of anticipation-associated loss of postural motor tone during long-term therapy. The effects of dexamphetamine alone (60 subjects), clomipramine alone (16 subjects) and combined dexamphetamine-clomipramine treatment (48 subjects) were evaluated. Self-reports indicated that the propensity to EDS was reduced by approximately 20% by dexamphetamine (mean dosage 16 mg/24 h, range 5-60: mean treatment period 21 years, range 2-45). The propensity to cataplexy was reduced by 23% by clomipramine (mean dosage 64 mg/24 h, range 25-125: mean treatment period 14 years, range 1-24). Dexamphetamine alone, in addition to reducing the propensity to EDS also reduced the propensity to cataplexy. Clomipramine alone reduced cataplexy, but not EDS. Combined dexamphetamine-clomipramine treatment caused a reduction in the propensity to EDS and cataplexy of similar magnitude to that caused by dexamphetamine alone. Less than 10% of all subjects with the narcoleptic syndrome reported a daytime sleep propensity in the normal range whilst on dexamphetamine and no subject on clomipramine reported complete control of cataplexy. Long-term treatment with dexamphetamine was associated with weight increase more commonly than weight loss. Weight gain was reported by two-thirds of subjects taking clomipramine alone. Reports of weight loss were as common as reports of weight gain by subjects on combined dexamphetamine-clomipramine treatment. Constipation, dry mouth and impaired sexual function were reported by 25%, 38% and 19% (respectively) of subjects on clomipramine. This retrospective long-term self-report study investigated the propensity to, rather than the frequency of, episodes of EDS and cataplexy in subjects with the narcoleptic syndrome. This study suggests that long-term drug treatment in the narcoleptic syndrome results in only minor reduction in attack propensity, in contrast to the findings of many previous short term objective studies, which suggest 50-80% reduction in attack frequency. Major factors limiting response to dexamphetamine in the narcoleptic syndrome include physician prescription of sub-optimal drug dosages, and a low index between the limited therapeutic efficacy and frequent side-effects of this drug.

Kawasaki disease (KD) is a pediatric systemic vasculitis of unknown etiology wherein genetic influence is suspected. Gene clusters within the HLA region at chromosome 6p21.3 have been linked to KD and other autoimmune disorders. As collagen is a strong autoantigen inducing chronic inflammation in patients with vasculitis, this study tests a hypothesis that single-nucleotide polymorphism (SNP) of a collagen gene, COL11A2, located in this HLA region may affect susceptibility to Kawasaki disease and its arterial sequels. SNP sites rs2294478 (at promoter) and rs2076311 (at intron 19) were genome-typed on 93 KD patients and 680 healthy subjects. Genotypic and allelic frequencies analyses found A allele at rs2076311 as a risk allele for KD. Clinical association study showed protective potential of C/C genotype at rs2294478 and A/A at rs2076311 for developing coronary artery lesions (CALs) in patients. In addition, C-A haplotype of COL11A2 gene associates with KD development and can serve as a genetic marker to differentiate KD patients lacking CALs from those with such lesions. Our findings suggest the involvement of genetic variations of COL11A2 in Kawasaki disease and CAL formation.

Rheumatoid arthritis (RA) is a chronic autoimmune disease and can lead to deformities and severe disabilities, due to irreversible damage of tendons, joints, and bones. A previous study indicated that a DNA repair system was involved in the development of RA. In this study, we investigated the association of four N-methylpurine-DNA glycosylase (MPG) gene polymorphisms (rs3176364, rs710079, rs2858056, and rs2541632) with susceptibility to RA in 384 Taiwanese individuals (192 RA patients and 192 control subjects). Our data show a statistically significant difference in genotype frequency distributions at rs710079 and rs2858056 SNPs between RA patients and control groups (P = 0.040 and 0.029, respectively). Our data also indicated that individuals with the GG genotype at rs2858056 SNP may have a higher risk of developing RA. In addition, compared with the haplotype frequencies between case and control groups, individuals with the GCGC haplotype appeared to be at a greater risk of RA progression (P = 0.003, OR = 1.75; 95% CI = 1.20-1.55). Our results suggest that rs710079 and rs2858056 polymorphisms and the GCGC haplotype in the MPG gene are associated with the risk of RA progression, and thus may be used as molecular markers of RA if they are confirmed by further research.