Biomedical subjects

Horng-Huei Liou

Publications and source records attributed to Horng-Huei Liou.

18 recordsLinked to original sources

PubMed2007

Simplified electrodiagnostic criteria of diabetic polyneuropathy in field study (KCIS No. 14).

This study sought to determine the sensitivity of sural sensory action amplitude (SAP) and peroneal motor conduction velocity (MCV) for differentiating the status of other nerve conduction velocities and identifying important correlates of diabetic polyneuropathy. Subjects (n = 708) with type 2 diabetes from one community completed a preliminary questionnaire. Among the 298 subjects with positive questionnaire results, 272 completed nerve conduction tests. The means of 6 nerve conduction velocities of subjects with both SAP and MCV abnormalities were compared to those of normal controls. The mean conduction velocities of all motor and sensory nerves were slower (p < 0.05) in subjects with polyneuropathy than without polyneuropathy. Important known correlates of diabetic polyneuropathy can also be identified by this electrophysiological definition. The sural SAP and peroneal MCV together serve as a good diagnostic for diabetic polyneuropathy and can be used as a simplified criterion in field studies.

Action Potentials↗

PubMed2006

Molecular and clinical analyses of 84 patients with tuberous sclerosis complex.

BACKGROUND: Tuberous sclerosis complex (TSC) is an autosomal dominant disease characterized by the development of multiple hamartomas in many internal organs. Mutations in either one of 2 genes, TSC1 and TSC2, have been attributed to the development of TSC. More than two-thirds of TSC patients are sporadic cases, and a wide variety of mutations in the coding region of the TSC1 and TSC2 genes have been reported. METHODS: Mutational analysis of TSC1 and TSC2 genes was performed in 84 Taiwanese TSC families using denaturing high-performance liquid chromatography (DHPLC) and direct sequencing. RESULTS: Mutations were identified in a total of 64 (76 %) cases, including 9 TSC1 mutations (7 sporadic and 2 familial cases) and 55 TSC2 mutations (47 sporadic and 8 familial cases). Thirty-one of the 64 mutations found have not been described previously. The phenotype association is consistent with findings from other large studies, showing that disease resulting from mutations to TSC1 is less severe than disease due to TSC2 mutation. CONCLUSION: This study provides a representative picture of the distribution of mutations of the TSC1 and TSC2 genes in clinically ascertained TSC cases in the Taiwanese population. Although nearly half of the mutations identified were novel, the kinds and distribution of mutation were not different in this population compared to that seen in larger European and American studies.

Adult↗

PubMed2006

Population-based survey on prevalence of adult patients with epilepsy in Taiwan (Keelung community-based integrated screening no. 12).

PURPOSE: To determine the prevalence rate and patterns of adult patients with epilepsy in Taiwan, we conducted a community-based neuroepidemiological survey. METHODS: Epilepsy was detected by neurologists using one-stage method. It was integrated into a community health screening service and performed from 1 January 2001 to 31 December 2001 in Keelung, a northern city in Taiwan. A total of 13,663 subjects aged 30 years or older participated in this survey. RESULTS: There were 52 patients with epilepsy in this study. Among them, 37 were patients with active epilepsy. The age-adjusted prevalence rate of active epilepsy above 30 years old was 2.77/1000 (to the 1980 US population) with the highest rate in subjects aged 40-49 years (4.0/1000). There was a trend of higher prevalence rate in male than in female. The most common seizure type was complex partial seizure (46.0%). Using one-stage detection method, we found nine (24.3%) patients with active epilepsy who had never been diagnosed before. Among the patients with active epilepsy, 35.1% were symptomatic cases. Head injury (13.5%) is the leading cause, followed by CNS infection (8.1%), stroke (5.4%) and perinatal insult (5.4%). The lifetime prevalence rate of epilepsy (including active epilepsy and epilepsy in remission) was 3.14/1000 for age above 30 years. CONCLUSIONS: Comparing to previous epilepsy survey in 1993, our results showed that the prevalence rate of epilepsy was rather stable over the past decade in northern Taiwan. Head injury is the leading cause responsible for active epilepsy. Improving public safety is an important public health issue which may help to reduce occurrence of epilepsy.

Adult↗

PubMed2006

A common polymorphism in the SCN1A gene associates with phenytoin serum levels at maintenance dose.

OBJECTIVES: A broad range of phenytoin doses is used in clinical practice, with the final 'maintenance' dose normally determined by trial and error. A common functional polymorphism in the SCN1A gene (one of the genes encoding the drug target) has been previously associated with maximum dose of phenytoin used clinically, and also maximum dose of carbamazepine, another antiepileptic drug with the same drug target. METHODS: We have related variation at the SCN1A IVS5-91 G>A polymorphism to maximum dose and to maintenance dose of phenytoin in 168 patients with epilepsy treated with phenytoin. We also related genotype to phenytoin serum levels at maximum dose and at maintenance dose of phenytoin. We genotyped the polymorphism using an Applied Biosystems Taqman assay. RESULTS: The polymorphism is associated with phenytoin serum concentration at maintenance dose (P=0.03). In a reduced cohort of 71 patients receiving phenytoin monotherapy this association is also significant (P=0.03). Neither association remains significant after Bonferroni correction for multiple testing. CONCLUSIONS: These results are not a replication of the original study. They do, however, support the hypothesis that this polymorphism influences the clinical use of phenytoin. They also demonstrate the utility of using multiple phenotypes in pharmacogenetics studies, particularly when attempting to separate pharmacokinetic and pharmacodynamic effects. As the SCN1A polymorphism affects phenytoin pharmacodynamics, it is particularly useful to obtain data on serum levels in addition to dose because association of a pharmacodynamic variant may be stronger with serum levels than dose as the serum level may eliminate or reduce pharmacokinetic variability.

Anticonvulsants↗

PubMed2005

Two-stage community-based screening model for estimating prevalence of diabetic polyneuropathy (KCIS no. 6).

The aim of this study was to apply a calibrated two-stage community-based design to estimate the prevalence of diabetic distal sensorimotor polyneuropathy (DPN) in Taiwan. Type 2 diabetics were identified from a population-based screening program in Keelung, Taiwan. Administration of the Neurological Symptom Score (NSS) questionnaire identified 210 DPN-positive cases of the 587 diabetic subjects tested. The accuracy of this NSS screening was tested with sensitive electrophysiological DPN diagnosis. A smaller validation study was also conducted to estimate the sensitivity and specificity of the NSS questionnaire. In the validation study, the overall prevalence rate for DPN among type 2 diabetics was 26.79%. The sensitivity, specificity, positive predictive value and negative predictive values were 73.33, 30.49, 24.72 and 75.76%, respectively. The estimates of sensitivity, specificity and positive predictive values were 75.00, 33.33 and 42.86% for old cases of diabetes, and 72.22, 29.69 and 22.41% for newly diagnosed cases. The range of prevalence rate in the main study was adjusted to 28.46-36.30% after calibration for sensitivity and specificity with the validation study data. A two-stage community-based screening model with calibration of prevalence rate was developed and enabled a cost-effective DPN prevalence rate estimate in a study with a large number of subjects.

Aged↗

PubMed2005

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.

Adult↗

PubMed2005

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.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2005

Mortality in adult patients with epilepsy in Taiwan.

To investigate mortality in adult patients with epilepsy in Taiwan, a total of 263 patients with epilepsy aged > or = 17 years, referred to the outpatient epilepsy clinic between 1 Jan and 31 December 1991, were prospectively enrolled and followed up until 31 December 2000. A total of 32 deaths were reported. Overall case-fatality rate was 12.2%. The age-adjusted standard mortality ratio (SMR) was calculated to compare the risk of death in patients with epilepsy to the general population. Patients with epilepsy had a 3.5-fold higher risk of death as compared with the general population (SMR: 3.47, 95% CI: 2.46-4.91). The Cox proportional hazards regression model was used to assess relevant clinical contributions to death. Patients with an age-at-onset > or = 40 years had a 4-fold higher risk of death as compared with those with an earlier onset. The multivariate analysis revealed that age-at-onset between 40 and 59 years, tumor etiology, and being male increased the risk of death in epilepsy. One-third of the deaths in patients with age-at-onset between 40-59 years died of liver cirrhosis and hepatoma. Hepatitis B virus infection is endemic in Taiwan, and this is closely associated with liver cirrhosis and hepatoma. Whether anticonvulsants contributed to the hepatotoxicity that led to fatal liver disease in this group needs further investigation.

Adult↗

PubMed2004

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

BACKGROUND: 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. METHODS: An integrated model of community-based multiple screening was designed and conducted between 1999 and 2001 in Keelung, Taiwan. The authors used a Papanicolaou (Pap) smear screening program as a base to integrate other screening regimens encompassing four other neoplastic diseases and three nonneoplastic chronic diseases. Screening methods, the interscreening interval, and the follow-up for each screening regimen were designed based on evidence-based literature and current national screening policy. RESULTS: A total of 42,387 subjects participated in the screening activities. A 25% increase in the attendance rate for Pap smear screening was demonstrated after the introduction of multiple disease screening programs. At the first screen, this program yielded a total of 677 asymptomatic neoplasms (16.0 per 1000), including a large proportion of precancerous lesions and small presymptomatic tumors without lymph node involvement. The association between the occurrence of neoplasm and the presence of comorbid nonneoplastic chronic disease was found to be statistically significant (odds ratio, 1.64; 95% confidence interval, 1.38-1.94 [P < 0.05]). The authors also identified 5314 subjects with metabolic syndrome who were at a greater risk for colorectal and oral neoplasias. CONCLUSIONS: The results of the current study demonstrate that an outreach and community-based multiple screening program not only enhances attendance rates but also has a high yield of early cases of various diseases simultaneously, and provides a natural opportunity to elucidate the correlation between neoplastic disease and nonneoplastic chronic disease.

Adult↗

PubMed2004

Estimation of prevalence and incidence of infantile spasms in Taiwan using capture-recapture method.

PURPOSE: To estimate the prevalence, incidence, and case-fatality of infantile spasms (IS) in Taiwan. METHODS: A retrospective cohort of patients with IS was obtained from one medical center to identify 69 IS cases from 1985 to 1997. This cohort, in conjunction with the claimed data from the National Health Insurance, was used to estimate the prevalence and incidence of IS by capture-recapture design, taking the case-fatality of IS into account. RESULTS: The prevalence rate of IS for aged 0-9 years was 0.046 per thousand. The incidence rate was estimated as 6 over 100,000 per year in Taiwan. Of the 69 IS cases, 8 deaths were ascertained. The case-fatality rate was 11.6%. The leading cause of death was status epilepticus. CONCLUSIONS: We have demonstrated an efficient method to estimate the incidence and prevalence rates of IS in Taiwan. Our results help to make a clear understanding of the disease burden of IS in this society.

Child↗

PubMed2004

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.

Adult↗

PubMed2004

Interaction between anticonvulsants and human placental carnitine transporter.

PURPOSE: To examine the inhibitory effect of anticonvulsants (AEDs) on carnitine transport by the human placental carnitine transporter. METHODS: Uptake of radiolabeled carnitine by human placental brush-border membrane vesicles was measured in the absence and presence of tiagabine (TGB), vigabatrin (VGB), gabapentin (GBP), lamotrigine (LTG), topiramate (TPM), valproic acid (VPA), and phenytoin (PHT). The mechanism of the inhibitory action of TGB was determined. RESULTS: Most of the AEDs inhibited placental carnitine transport. Kinetic analyses showed that TGB had the greatest inhibitory effect [50% inhibitory concentration (IC50, 190 microM)], and the order of inhibitory potency was TGB > PHT > GBP > VPA > VGB, TPM > LTG. Further studies showed that TGB competitively inhibited carnitine uptake by the human placental carnitine transporter, suggesting that it may be a substrate for this carrier. CONCLUSIONS: Although the involvement of carnitine deficiency in fetal anticonvulsant syndrome requires further evaluation, potential interference with placental carnitine transport by several AEDs was demonstrated. Despite the higher inhibitory potency of TGB, given the therapeutic unbound concentrations, the results for VPA and PHT are probably more clinically significant.

Acetates↗

PubMed2003

Treatment of advanced Parkinson's disease by subthalamotomy: one-year results.

We studied effects on parkinsonian features at 6 and 12 months in 12 patients who underwent unilateral ablation of subthalamic nucleus (STN). Microelectrode mapping was used, and a lesion was created in the STN using thermal coagulation and confirmed with magnetic resonance imaging. At 6 months postoperatively, improvements were seen in several areas: 1) Unified Parkinson's Disease Rating Scales II and III (UPDRS II and III) scores, 30% in off period, 38% in on period; 2) Schwab and England Scale (S&E) score, 21%; and 3) on dyskinesia, 85%. Contralateral rigidity, bradykinesia, UPDRS II and III scores, and S&E scores remained improved at 12 months. Daily dosage of levodopa requirement was reduced by 42%. Axial motor features, gait, postural stability, off period tremor, and motor fluctuation improved at 6 and 12 months but showed a decline in benefits at 18 months. Complications include 3 cases of hemiballism, of whom 2 patients recovered spontaneously but 1 died from aspiration pneumonia. One patient had asymptomatic hematoma, and 2 suffered transient postural asymmetries. We conclude that unilateral subthalamotomy results in moderate improvement in all aspects of parkinsonian features, allows reduction in the dose of levodopa required, and ameliorates drug-induced complications throughout 12-month assessments.

Adult↗

PubMed2003

Structural basis of binding and inhibition of novel tarantula toxins in mammalian voltage-dependent potassium channels.

Voltage-dependent potassium channel Kv2.1 is widely expressed in mammalian neurons and was suggested responsible for mediating the delayed rectifier (I(K)) currents. Further investigation of the central role of this channel requires the development of specific pharmacology, for instance, the utilization of spider venom toxins. Most of these toxins belong to the same structural family with a short peptide reticulated by disulfide bridges and share a similar mode of action. Hanatoxin 1 (HaTx1) from a Chilean tarantula was one of the earliest discussed tools regarding this and has been intensively applied to characterize the channel blocking not through the pore domain. Recently, more related novel toxins from African tarantulas such as heteroscordratoxins (HmTx) and stromatoxin 1 (ScTx1) were isolated and shown to act as gating modifiers such as HaTx on Kv2.1 channels with electrophysiological recordings. However, further interaction details are unavailable due to the lack of high-resolution structures of voltage-sensing domains in such mammalian Kv channels. Therefore, in the present study, we explored structural observation via molecular docking simulation between toxins and Kv2.1 channels based upon the solution structures of HaTx1 and a theoretical basis of an individual S3(C) helical channel fragment in combination with homology modeling for other novel toxins. Our results provide precise chemical details for the interactions between these tarantula toxins and channel, reasonably correlating the previously reported pharmacological properties to the three-dimensional structural interpretation. In addition, it is suggested that certain subtle structural variations on the interaction surface of toxins may discriminate between the related toxins with different affinities for Kv channels. Evolutionary links between spider peptide toxins and a "voltage sensor paddles" mechanism most recently found in the crystal structure of an archaebacterial K(+) channel, KvAP, are also delineated in this paper.

Amino Acid Sequence↗

PubMed2002

Postural asymmetries following unilateral subthalomotomy for advanced Parkinson's disease.

Two cases of postural asymmetries following unilateral stereotaxic subthalamotomy were observed with head and body tilting to the side contralateral to the STN lesion, which corrected itself completely or partially with levodopa treatment. After subsequent contralateral STN surgery, the postural asymmetry disappeared in both patients. Possible mechanism is discussed.

Brain↗

PubMed2002

Structural determinants and specificities for ROMK1-phosphoinositide interaction.

We have recently reported that direct interaction between phosphatidylinositol bisphosphate (PIP(2)) and the COOH-terminal cytoplasmic domain of ROMK1 is important for opening of the channel. We identified arginine-188 of ROMK1 as a critical residue for this interaction. Here, we further report that substitution of a neutral amino acid for lysine-181, arginine-217, or lysine-218 decreases single-channel open probability for the full-conductance state and increases the frequency of opening at a subconductance state. Compared with wild-type ROMK1 channels, these substitution mutants also display an increased sensitivity to the block by anti-PIP(2) antibodies and to inhibition by intracellular protons. These results indicate that, like arginine-188, lysine-181, arginine-217, and lysine-218 are also involved in interactions with PIP(2) and are critical for ROMK1 to open at full conductance. Using synthetic phosphoinositides containing phosphates at different positions in the head group, we also examined the specificities of phosphoinositides in the regulation of ROMK1 channels. We found that phosphoinositides containing phosphate at both positions 4 and 5 of the inositol head group have the highest efficacy in activating ROMK1 channels. These results suggest that phosphatidylinositol 4,5-bisphosphate is likely the important phosphoinositide in the regulation of ROMK1 channels in a physiological membrane milieu.

Alanine↗

PubMed2002

Subthalamotomy for advanced Parkinson disease.

OBJECT: The aim of this study was to determine if subthalamotomy is effective in treating advanced Parkinson disease (PD). METHODS: The authors performed microelectrode mapping-guided stereotactic surgery on the subthalamic nucleus in eight patients with PD. Lesioning was performed using radiofrequency heat coagulation and confirmed with magnetic resonance imaging. Three patients who underwent unilateral and four with bilateral subthalamotomy were evaluated for up to 18 months according to the Unified PD Rating Scale (UPDRS). One patient who underwent unilateral subthalamotomy died 6 months postsurgery. At 3 months into the "off" period after surgery, there were significant improvements in contralateral bradykinesia (p < 0.0002), rigidity (p < 0.0001), tremor (p < 0.01), axial motor features (p < 0.02), gait (p < 0.03), postural stability (p < 0.03), total UPDRS scores (p < 0.03), and Schwab and England scores (p < 0.04). The benefits were sustained at 6, 12, and 18 months, except for the improvement in tremor. At 12 months into the "on" period, significant benefits were present for motor fluctuation (p < 0.04), on dyskinesia (p < 0.006), off duration (p < 0.05), total UPDRS score (p < 0.02), and contralateral tremor (p < 0.05). Benefits for motor fluctuation, off duration, and off-period tremor were lost after the 18-month follow-up period. The levodopa requirement was reduced by 66% for the unilateral and 38% for the bilaterally treated group. Bilateral subthalamotomy offered more benefits than did unilateral surgery for various parkinsonian features in both the on and off periods. Three patients suffered hemiballismus, two recovered spontaneously, and one died of aspiration pneumonia after discontinuation of levodopa. CONCLUSIONS: These findings indicate that subthalamotomy can ameliorate the cardinal symptoms of PD, reduce the dosage of levodopa, diminish complications of the drug therapy, and improve the quality of life.

Aged↗

PubMedDate not supplied

A possible molecular mechanism of hanatoxin binding-modified gating in voltage-gated K+-channels.

While S4 is known as the voltage sensor in voltage-gated potassium channels, the carboxyl terminus of S3 (S3C) is of particular interest concerning the site for gating modifier toxins like hanatoxin. The thus derived helical secondary structural arrangement for S3C, as well as its surrounding environment, has since been intensively and vigorously debated. Our previous structural analysis based on molecular simulation has provided sufficient information to describe reasonable docking conformation and further experimental designs (Lou et al., 2002. J. Mol. Recognit. 15: 175-179). However, if one only relies on such information, more advanced structure-functional interpretations for the roles S3C may play in the modification of gating behavior upon toxin binding will remain unknown. In order to have better understanding of the molecular details regarding this issue, we have performed the docking simulation with the S3C sequence from the hanatoxin-insensitive K+-channel, shaker, and analyzed the conformational changes resulting from such docking. Compared with other functional data from previous studies with respect to the proximity of the S3-S4 linker region, we suggested a significant movement of drk1 S3C, but not shaker S3C, in the direction presumably towards S4, which was comprehended as a possible factor interfering with S4 translocation during drk1 gating in the presence of toxin. In combination with the discussions for structural roles of the length of the S3-S4 linker, a possible molecular mechanism to illustrate the hanatoxin binding-modified gating is proposed.

Binding Sites↗