Carbamazepine-induced toxic effects and HLA-B*1502 screening in Taiwan.

BACKGROUND: Carbamazepine, an anticonvulsant and a mood-stabilizing drug, is the main cause of the Stevens-Johnson syndrome (SJS) and its related disease, toxic epidermal necrolysis (TEN), in Southeast Asian countries. Carbamazepine-induced SJS-TEN is strongly associated with the HLA-B*1502 allele. We sought to prevent carbamazepine-induced SJS-TEN by using HLA-B*1502 screening to prospectively identify subjects at genetic risk for the condition. METHODS: From 23 hospitals in Taiwan, we recruited 4877 candidate subjects who had not taken carbamazepine. We genotyped DNA purified from the subjects' peripheral blood to determine whether they carried the HLA-B*1502 allele. Those testing positive for HLA-B*1502 (7.7% of the total) were advised not to take carbamazepine and were given an alternative medication or advised to continue taking their prestudy medication; those testing negative (92.3%) were advised to take carbamazepine. We interviewed the subjects by telephone once a week for 2 months to monitor them for symptoms. We used the estimated historical incidence of SJS-TEN as a control. RESULTS: Mild, transient rash developed in 4.3% of subjects; more widespread rash developed in 0.1% of subjects, who were hospitalized. SJS-TEN did not develop in any of the HLA-B*1502-negative subjects receiving carbamazepine. In contrast, the estimated historical incidence of carbamazepine-induced SJS-TEN (0.23%) would translate into approximately 10 cases among study subjects (P<0.001). CONCLUSIONS: The identification of subjects carrying the HLA-B*1502 allele and the avoidance of carbamazepine therapy in these subjects was strongly associated with a decrease in the incidence of carbamazepine-induced SJS-TEN. (Funded by the National Science Council of Taiwan and the Taiwan Drug Relief Foundation.).

Association of apolipoprotein E polymorphism with ischemic stroke subtypes in Taiwan.

The aim of this study was to clarify whether the apolipoprotein E gene (APOE) is related to ischemic stroke subtypes in Taiwan's Chinese population. Using the classification of Cerebrovascular Diseases III, 143 patients with lacunar infarction, 114 patients with atherothrombotic infarction, and 112 healthy controls were enrolled. APOE genotype was determined using polymerase chain reaction. Regarding the distribution of APOE genotypes, the frequency of epsilon3/epsilon4 genotypes in lacunar patients was significantly different from that in control subjects, by logistic regression, using epsilon3/epsilon3 as a reference group. There was no significant difference between atherothrombotic patients and the control group in the distribution of APOE genotypes or alleles. The present finding suggests that there is a probable association between epsilon3/epsilon4 genotype and lacunar infarcts, but not atherothrombotic infarcts. This indicates that genetic factors may play a role, at least partially, in lacunar infarction in Taiwan's Chinese population.

Simple and sensitive liquid chromatographic method with fluorimetric detection for the analysis of gabapentin in human plasma.

A simple and sensitive liquid chromatographic method is described for the quantitative analysis of gabapentin in human plasma. Gabapentin (GBP) is an anticonvulsant and widely used in the treatment of epilepsy. No peculiar chromophore is available on gabapentin moiety for direct analysis by absorption spectrophotometry. In human plasma after deproteinisation with acetonitrile, gabapentin was derivatized with a fluorescent reagent, (2-naphthoxy)acetyl chloride (NAC) in borate buffer (pH 10.0). The resulting naphthoxy derivative of gabapentin was separated on a phenyl-hexyl column with a mobile phase consisting of a mixture of sodium acetate buffer (100 mM; pH 5.0)-methanol (32:68, v/v) used in isocratic mode. Using fluorimetric detection (excitation at 225 nm and emission at 360 nm), a low detection limit of about 0.04 microM (S/N = 3, 10 microl injected) was reached. The relative standard deviations (RSD) of the method for intra- and inter- day analyses (n = 5) are between 2.7 and 4.0%, respectively. The method was successfully applied to the analysis of gabapentin in plasma from dosed patients for therapeutic drug monitoring.

Relationship between event-related potentials and frontal-subcortical dysfunction in Parkinson's disease.

Cognitive impairment in Parkinson's disease (PD) has been determined to be due to the interruption of frontal-subcortical neural circuits. To evaluate which kind of frontal-subcortical dysfunction may be present and the relationship of this dysfunction with P300 in PD patients, non-demented PD patients and controls were rendered for comprehensive Frontal Test Battery and P300 assessments. PD patients manifested significantly with frontal dysfunction and revealed a good correlation between P300 and executive dysfunction. We conclude that PD patients may manifest with cognitive impairment related to frontal dysfunction, and P300 may be an indicator reflecting the evolution of dysexecutive syndrome.

Cut-off values of blessed dementia rating scale and its clinical application in elderly Taiwanese.

Although the Blessed Dementia Rating Scale (BDRS), a clinical screening instrument, has been applied extensively, no suitable cut-off values and clinical application have been proposed, particularly in mild cognitive impairment (MCI), the precursor of dementia. The BDRS, Mini Mental State Examination (MMSE), and Clinical Dementia Rating Scale (CDR) were administrated in people aged 65 years and above, who were enrolled from southern Taiwan with multistep stratified random sampling and followed-up for 2 years. All subjects (total number = 3,027), with new onset of MCI (defined as CDR = 0.5) in the first year and dementia (defined as CDR > or = 1) in the second and third years were subjected to statistical analysis. In distinguishing normal from MCI, except in the literate group aged 65-74 years, MMSE was superior to BDRS, with cut-off values of 1 in both literate groups aged 65-74 years and > or = 75 years, and 1.5 and 2 in less educated groups aged 65-74 and > or = 75 years, respectively. In distinguishing MCI from dementia, BDRS had cut-off values of 2.5 in both literate groups aged 65-74 and > or = 75 years, and 2.5 and 3 in less educated groups aged 65-74 and > or = 75 years, respectively. These values were better than those for MMSE in all groups. BDRS might be considered as a better tool than MMSE to screen for MCI and dementia in the increasing proportion of literate elderly aged 65-74 years in the aging population.

Tuberculous meningitis with initial manifestation of isolated oculomotor nerve palsy.

Tuberculous meningitis (TB meningitis) is a subacute meningitis known for its various form of initial manifestations, which often make early diagnosis difficult. The present case report demonstrates a patient with TB meningitis, who had initial manifestation of isolated right oculomotor nerve palsy. High vigilance is needed in diagnosing TB meningitis. A 75 year-old female was hospitalized due to acute onset of right side ptosis. Thorough neurological examination at admission revealed isolated right oculomotor nerve palsy. Brain magnetic resonance imaging and cerebral angiography showed no specific finding. Lumbar puncture was performed two days later due to low grade fever. Cerebrospinal fluid (CSF) study and the polymerase chain reaction on CSF confirmed the diagnosis of TB meningitis. Because TB meningitis is a chronic disease, cranial nerve palsies are common manifestations. This report suggests that TB meningitis should be a disease of differential diagnosis for isolated oculomotor nerve palsy.

Cognitive dysfunction after acute lacunar infarct.

Vascular dementia and vascular cognitive impairment have attracted more attention recently due to their association with increased risk of death and institutionalization. The purpose of the present study was to detect and identify the characteristics of cognitive impairments during the early stage of lacunar stroke. The subjects consisted of 23 consecutive first-ever acute lacunar infarction patients who were admitted to the Department of Neurology, Kaohsiung Municipal Hsiao-Kang Hospital, Taiwan, from November 2001 to October 2002. The National Institutes of Health Stroke Scale and Cognitive Abilities Screening Instrument (CASI) were used to evaluate stroke severity and cognitive function, and assessments were performed by a neurologist and psychologist, within 10 days of stroke onset. Of the 23 patients, 21 (91.3%) had CASI scores below their respective cutoff values and all patients had cognitive impairment in at least one cognitive domain in CASI. There were no significant correlations between CASI abnormality (below the cutoff value) and patient age, education, or the interval from stroke onset. Recent memory impairment was the most often impaired cognitive domain on CASI (19 patients, 82.6%). There were significant correlations between recent memory and "attention or concentration"(correlation coefficient, 0.52; p < 0.05), and "abstraction and judgment" (correlation coefficient, 0.44; p < 0.05). The correlations between recent memory and other domains were not significant. It was concluded that cognitive impairment after acute lacunar infarct is quite common and recent memory is the most often impaired cognitive domain. This may have been caused by the location of the specific lesion as well as by the impairment in "attention or concentration" or "abstraction and judgment".

Chromosome 9p21 genetic variants are associated with myocardial infarction but not with ischemic stroke in a Taiwanese population.

BACKGROUND: Genetic variants on chromosome 9p21 confer a robust risk for coronary artery disease but inconsistent risk for stroke. This study investigated whether such genetic variants exert differential risks on myocardial infarction (MI) and ischemic stroke in a Taiwanese population. METHODS: The study recruited 425 MI patients, 687 patients with ischemic stroke, and 1377 healthy controls. Four key single nucleotide polymorphisms (SNPs) on chromosome 9p21 were genotyped. RESULTS: Multivariate permutation analyses demonstrated that the risk T allele of rs1333040 and G allele of rs2383207 were associated with MI (P = 0.045 and 0.002, respectively). Subjects with the rs2383207 GG genotype had a 1.85-fold (P = 0.021) risk for MI when compared with the subjects with the AA genotype. Further analysis showed that significant results only exist in the young MI group (<65 years) but not in the old MI group (≥65 years). These SNPs were not statistically significant for stroke (adjusted P ranged from 0.097 to 0.540). Haplotype analysis showed global P values of 0.032 for MI and 0.290 for stroke. CONCLUSIONS: Genetic variations in the 9p21 region are associated with MI but not with stroke in a Taiwanese population. Early-onset MI was more likely to carry the risk genotypes of 9p21 SNPs.

Apolipoprotein E polymorphism in ischemic cerebrovascular diseases and vascular dementia patients in Taiwan.

This study aims to clarify the association between apolipoprotein E gene (ApoE) polymorphism, ischemic cerebrovascular diseases (ICVD) and vascular dementia (VaD) in Taiwan Chinese. 277 patients with ICVD, 49 patients with probable VaD and 112 controls were recruited for this study. Distributions of ApoE epsilon4 carriers and allele frequencies were 28.5 and 14.5% for patients with ICVD, 20.4 and 10.2% for patients with VaD, whereas these values were 22.9 and 11.6% for controls. Distributions of ApoE epsilon2 carriers and allele frequencies were 10.1 and 5.2% for ICVD patients, 6.1 and 3.1% for VaD patients, but 12.5 and 8.0% for controls. There were no differences between ICVD patients and controls, or VaD patients and controls in their epsilon4 carriers. Those patients aged 65 and under, carrying the epsilon2 allele, had a lower risk of developing ICVD and VaD than did their counterparts. These findings suggest that ApoE epsilon4 plays no significant role in the development of ICVD and VaD, but that ApoE epsilon2 has a protective effect with regard to the development of ICVD and VaD for Taiwan Chinese below the age of 65.