Horng-Huei Liou

Environmental risk factors and Parkinson's disease A case‐control study in Taiwan

To explore environmental risk factors for Parkinsons disease (PD) in Taiwan, we investigated 120 patients with PD and 240 hospital control subjects matched with patients on age (± 2 years) and sex. Based on a structured open-ended questionnaire, we carried out standardized interviews to obtain history of exposure to environmental factors, including place of residence, source of drinking water, and environmental and occupational exposures to various agricultural chemicals. In the univariate analysis, the history of living in a rural environment, farming, use of herbicides/pesticides, and use of paraquat were associated with an increased PD risk in a dose-response relationship. After adjustment for multiple risk factors through conditional logistic regression, the biological gradient between PD and previous uses of herbicidesipesticides and paraquat remained significant. The PD risk was greater among subjects who had used paraquat and other herbicide/pesticides than those who had used herbicides/pesticides other than paraquat. There were no significant differences in occupational exposures to chemicals, heavy metals, and minerals between PD patients and matched control subjects. The duration of drinking well water and alcohol consumption was not significantly associated with PD. There was an inverse relationship between cigarette smoking and PD. Environmental factors, especially exposures to paraquat and herbicides/pesticides, may play important roles in the development of PD in Taiwan.

Complex haplotypic effects of the ABCB1 gene on epilepsy treatment response.

OBJECTIVES The aim of this study was to investigate the association of the complex haplotype system of the adenosine triphosphate-binding cassette B1 (ABCB1) gene with the epilepsy treatment response. METHODS AND RESULTS Ten polymorphisms were genotyped in 108 drug-resistant epileptic patients, 223 seizure-free patients and 287 normal controls. Highly significant linkage disequilibrium was shown among exon 12 C1236T, exon 21 G2677T and exon 26 C3435T. Haplotypic analysis demonstrated that patients with the CGC, TGC, and TTT haplotypes were more likely to be drug resistant. Further analysis of haplotype combinations demonstrated that drug-resistant patients tended to have the CGC/CGC, CGC/TGC, CGC/TTT, and TGC/TTT haplotype combinations over the seizure-free patients and controls (all p-values < 0.0001). In contrast, patients with the TTC/TTC, TTC/CGT, TTC/TGT, CGT/CGT and TGT/CGT haplotype combinations were more likely to be seizure-free (all p-values<0.0001 except CGT/CGT [p=0.0063]). CONCLUSION Our results showed that the three loci, C1236T, G2677T and C3435T, jointly influenced the treatment response for epileptic patients. They should be regarded together as a complex polymorphic drug-response system. These findings suggest that examination of the haplotypes of the three loci could be useful in predicting drug resistance in epilepsy.

Community-based multiple screening model†‡§¶

Multiple disease screening may have several advantages over single disease screening because of the economics of scale, with the high yield of detecting asymptomatic diseases, the identification of multiple diseases or risk factors simultaneously, the enhancement of the attendance rate, and the efficiency of follow‐up.

Prevalence, incidence, and mortality of PD: A door-to-door survey in Ilan County, Taiwan

Background: The reported prevalence and incidence rates of PD were significantly lower in China than those in Western countries. People in China and Taiwan have a similar ethnic background. Objective: To investigate the prevalence, incidence, and mortality rate of PD in Taiwan. Method: The authors conducted a population-based survey using a two-stage door-to-door approach for patients aged 40 years or older in Ilan, Taiwan. Patients were diagnosed with PD by having at least two of the four cardinal signs of parkinsonism and exclusion of seconddary parkinsonism. To identify new cases of PD after the survey, patients with negative results of parkinsonism in the first stage were matched to the information on clinical diagnosis of PD from the Bureau of National Health Insurance toward the end of December 31, 1997. All cases of PD were linked to the Taiwan mortality registration to ascertain causes of deaths until December 31, 1999. Results: The participation rate was 88.1% among the 11,411 contacted individuals. Thirty-seven cases of PD were identified. The age-adjusted prevalence rate of PD for all age groups was 130.1 per 100,000 population after being adjusted to the 1970 US census, assuming no cases of PD would be found among those younger than 40 years of age. Of 9972 non-PD subjects in the first screen, 15 new cases of PD were ascertained. The age-adjusted incidence rate was 10.4 per 100,000 population for all age groups. The case fatality rate of PD after a 7-year follow-up was 40.4% (21 deaths in 52 patients with PD). The relative risk of death for PD cases versus non-PD cases was 3.38 (95% CI: 2.05–4.34). The 5-year cumulative survival rate in PD cases (78.85%) was statistically lower than that in non-PD cases (92.84%). Conclusion: The prevalence and incidence rates of PD in Taiwan were much higher than those reported in China, but closer to those in Western countries. These results suggest that environmental factors may be more important than racial factors in the pathogenesis of PD.

Dosage Recommendation of Phenytoin for Patients with Epilepsy with Different Cyp2c9/cyp2c19 Polymorphisms

To search for the optimal dosage of phenytoin in patients with epilepsy based on the metabolic activities of CYP2C9 and CYP2C19 polymorphisms, a total of 169 patients receiving phenytoin treatment for more than 1 month were recruited. Phenytoin concentration, serum albumin, liver function tests, and renal function tests were measured. CYP2C9 and CYP2C19 polymorphisms were genotyped by PCR-RFLP analysis, and NONMEM models were built to evaluate factors that would affect phenytoin metabolism. Patients were divided into 5 groups according to genotyping results (G1 to G5). Compared with extensive metabolizers in both CYP2C9 and CYP2C19 (G1), the Vmax (mg/kg/d) was 8.29% and 36.96% lower in CYP2C19 poor metabolizers (G3) and CYP2C9 poor metabolizers (G4), respectively. For the patient who was identified as a poor metabolizer in both CYP2C19 and CYP2C9 (G5), the Vmax was 45.75% lower than that of G1. In respect to Km (mg/L), it was 15.09% higher in G3 and 27.36% higher in G4 compared with that in G1. The Km of G5 was 91.71% higher than that of G1. The results revealed that the CYP2C9 and CYP2C19 polymorphisms have dramatic effects on the population pharmacokinetic parameters of phenytoin, especially for CYP2C9. Based on the Vm and Km values obtained in this study, the recommended dose ranges for G1, G2, G3, G4, and G5 patients would be 5.5–7, 5–7, 5–6, 3–4, and 2–3 mg/kg/d, respectively.

Anticardiolipin antisera from lupus patients with seizures reduce a GABA receptor-mediated chloride current in snail neurons

The effects of circulating anticardiolipin (ACL) antisera in lupus patients on the LP5 central neuron of snail were studied. Both GABA and glutamate increased a chloride conductance of the LP5 neuron. The ACL antisera decreased the GABA-elicited responses in a concentration dependent manner while it had no effect on glutamate-elicited responses. The ACL antisera affected neither the resting membrane current, nor the membrane conductivity of neuron. Antisera without the activity of anticardiolipin did not decrease the GABA-elicited responses. The seizure incidence of the patients with higher ACL antisera levels is also higher. It is concluded that ACL antisera inhibited the GABA ionophore receptor complex in a snail central neuron.

Community-based multiple screening model: design, implementation, and analysis of 42,387 participants.

Multiple disease screening may have several advantages over single disease screening because of the economics of scale, with the high yield of detecting asymptomatic diseases, the identification of multiple diseases or risk factors simultaneously, the enhancement of the attendance rate, and the efficiency of follow‐up.

Cellular localization of the organic cation transporters, OCT1 and OCT2, in brain microvessel endothelial cells and its implication for MPTP transport across the blood-brain barrier and MPTP-induced dopaminergic toxicity in rodents

J. Neurochem. (2010) 114, 717–727.

Health related quality of life in adult patients with epilepsy compared with a general reference population in Taiwan

To compare the health-related quality of life (HRQL) for patients with epilepsy and health subjects, we collected the clinical and demographic data and information on health states by using the Taiwan version of World Health Organization quality of life (WHOQOL)-BREF questionnaire in 296 patients (aged 19-73 years) with confirmed active epilepsy visiting the clinic of National Taiwan University Hospital, and 296 age-, gender-, municipal- and education-matched Taiwanese healthy subjects sampled from a national health interview survey. Multiple regression analyses with stepwise selection strategy were conducted to study risk factors for impairment of HRQL. Patients with epilepsy have poorer HRQL than the healthy population in physical, psychological and social domains but not in environment domain (p<0.005). Patients with less than 4 attacks during the previous 1 month had a better score in the availability and quality of health and social care in environment domain than healthy subjects (p<0.05). After controlling other determinants, seizure frequency, and comobid with other diseases are the important factors in predicting HRQL for epilepsy patients. Patients with employment and married had a significantly better HRQL. Effective control of seizure frequency and thoughtful promotion of positive attitudes in community are essential to improve the HRQL of epilepsy patients.

Lamotrigine inhibits postsynaptic AMPA receptor and glutamate release in the dentate gyrus

Purpose: The dentate gyrus (DG) is a gateway that regulates seizure activity in the hippocampus. We investigated the site of action of lamotrigine (LTG), an effective anticonvulsant, in the regulation of alpha‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid (AMPA) and N‐methyl‐D‐aspartic acid (NMDA) receptor‐mediated excitatory synaptic transmission on DG.