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Biomedical subjects

Nigel C K Tan

Publications and source records attributed to Nigel C K Tan.

7 recordsLinked to original sources
PubMed2006

Acute symptomatic seizures and hippocampus damage: DWI and MRS findings.

The authors describe diffusion-weighted imaging (DWI) and magnetic resonance spectroscopy (MRS) changes in the hippocampus within 48 hours of acute symptomatic seizures or status epilepticus in 12 patients. DWI showed increased signal and a decreased apparent diffusion coefficient (ADC) in all patients, with corresponding lactate detected on MRS in six patients and EEG seizure activity in nine patients. On follow-up, the atrophic hippocampus had an increased ADC in six patients. DWI and MRS may predict development of hippocampal sclerosis.

Adolescent↗
PubMed2006

Determinants of epidermal nerve fiber density in normal individuals.

We studied the relationship between epidermal innervation and age, gender, height, and weight. Intraepidermal nerve fiber density (IENFD) of skin biopsies obtained from the proximal thigh and ankle of 84 normal individuals was quantified. A linear regression model was performed using IENFD at the thigh, IENFD at the ankle, and the thigh IENFD/ankle IENFD ratio, with age, gender, and height-weight interaction as predictors. An independent, negative correlation was found between age and IENFD at the ankle. No correlation was found between age and IENFD at the thigh. With increasing age the thigh IENFD/ankle IENFD ratio, a measure of the length-dependent distal-to-proximal gradient of epidermal nerve density, increased significantly. Gender, height, and body weight did not independently influence IENFD at either site. In normal individuals, distal epidermal innervation decreases in a length-dependent manner with advancing age. This must be considered when interpreting IENFD in disease states.

Adult↗
PubMed2006

Genetic dissection of the common epilepsies.

PURPOSE OF REVIEW: Only two functionally validated susceptibility genes, CACNA1H and GABRD, have so far been identified in the common epilepsies using a candidate gene approach. The difficulty with the alternative statistical approach, where none of the suggested candidates has been functionally validated, may partly be due to the posited genetic architecture of the common epilepsies, such as the idiopathic generalized epilepsies. A subset of both rare and common variants from a much larger pool of susceptibility genes may contribute to disease risk. We review methods and designs for the genetic dissection of common epilepsies. RECENT FINDINGS: Genetic association studies, though theoretically more powerful than linkage analysis, have not yet delivered validated susceptibility genes. Methodological flaws can undermine such studies but are correctable. Concerns remain, however, about the extent of underlying genetic heterogeneity in common epilepsies. Genome-wide association studies are increasingly feasible, but issues remain about their conduct and analysis. Meta-analysis may resolve conflicting association studies, facilitated by the establishment of databases of genetic association studies. Newer multi-locus and admixture mapping approaches are attractive alternatives to traditional association studies and may offer new insights into identifying epilepsy genes. SUMMARY: We conclude by emphasizing the importance of deeper endophenotyping using electroclinical, imaging, and molecular approaches to dissect the common epilepsies.

Chromosome Mapping↗
PubMed2005

Is variation in the GABA(B) receptor 1 gene associated with temporal lobe epilepsy?

PURPOSE: gamma-Aminobutyric acid (GABA)-receptor genes are prime candidates for a role in seizure susceptibility. An association between the c.1465G-->A variant in the GABA(B) receptor 1 gene (GABBR1) and susceptibility to temporal lobe epilepsy (TLE) has been reported in an Italian cohort. We sought to replicate this association in an independent Australian cohort. METHODS: The 234 patients with TLE and 164 healthy controls were genotyped for the c.1465G-->A variant, by using inclusion criteria identical to those of the first study. RESULTS: The c.1465G-->A variant was found in one TLE patient and one control subject. Genotype and allele frequencies did not differ between groups. CONCLUSIONS: We did not replicate the reported associations between the c.1465G-->A variant and susceptibility to TLE. We suggest that the initial positive association may be due to undetected population stratification; the importance of genomic control is emphasized. Population-specific effects also may play a role, and we highlight the need to demonstrate an in vitro functional effect to give biologic meaning to any proposed association.

Adolescent↗
PubMed2004

Genetic association studies in epilepsy: "the truth is out there".

Success has been achieved in identifying many mutations in rare monogenic epilepsy syndromes by using linkage analysis, but dissecting the genetic basis of common epilepsy syndromes has proven more difficult. Common epilepsies are genetically complex disorders believed to be influenced by variation in several susceptibility genes. Association studies can theoretically identify these genes, but despite more than 50 association studies in epilepsy, no consistent or convincing susceptibility genes have emerged, leading to scepticism about the association-study approach. We review the results of existing association studies in focal epilepsies, generalized epilepsies, febrile seizures, and epilepsy pharmacogenetics. By using an illustrative example, we discuss how methodologic issues of sample size, selection of appropriate controls, population stratification, and significance thresholds can lead to bias and false-positive associations; the importance of biologic plausibility also is emphasized. Newer methodologic refinements for association studies, such as use of two control groups, genomic control, haplotyping, and use of two independent datasets, are discussed. A summary of existing guidelines and a checklist for planning and appraising such association studies in epilepsy is presented. We remain cautiously optimistic that with methodologic refinements and multicenter collaborations with large sample sizes, association studies will ultimately be useful in dissecting the genetic basis of common epilepsy syndromes.

Chromosome Mapping↗
PubMed2004

Systemic autonomic function in subjects with primary angle-closure glaucoma: a comparative study of symptomatic and asymptomatic disease presentation.

BACKGROUND: Autonomic dysfunction is thought to be a contributory factor in primary angle-closure glaucoma (PACG) by precipitating pupil block in anatomically predisposed eyes. This study aimed to compare systemic autonomic function between subjects who had suffered a previous episode of acute angle closure (symptomatic PACG), those who had asymptomatic PACG, and age and sex-matched controls. METHODS: Tests for systemic parasympathetic function included the heart-rate response to standing (30:15 ratio), heart-rate variation during deep breathing, and the ratio of the heart rate at phases IV and II of the Valsalva manoeuvre (Valsalva ratio). For assessment of the sympathetic nervous system, blood pressure was recorded supine and then after 2 and 5 min of standing. A modified sweat test, the sympathetic skin response, was recorded on the palm and sole. RESULTS: A total of 30 subjects were examined: eight previous symptomatic PACG, eight asymptomatic PACG and 14 control subjects. The mean ages were similar, and all except one subject were Chinese. None of the subjects had evidence of systemic dysautonomia. There was no significant difference found between the groups for the 30:15 ratio, heart-rate variation during deep respiration and the Valsalva ratio. No significant orthostatic hypotension was detected in subjects with PACG. Abnormal sympathetic skin response was not more common in PACG subjects compared to control subjects. CONCLUSIONS: This study identified no systemic autonomic dysfunction in people with PACG.

Autonomic Nervous System↗