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Biomedical subjects

S Fook-Chong

Publications and source records attributed to S Fook-Chong.

At least 19 recordsLinked to original sources
PubMed2006

Comparing knowledge and attitudes towards genetic testing in Parkinson's disease in an American and Asian population.

INTRODUCTION: Recent discoveries of disease-causing genes in Parkinson's disease (PD) have generated considerable interest regarding genetic testing in PD. The attitudes toward genetic testing are largely influenced by knowledge and preconceived notions. OBJECTIVE: We investigated the relationship between knowledge of and attitude towards predictive genetic testing of PD in two independent centers in America and Asia involving PD patients and caregivers. METHODS: In a prospective study involving 515 subjects comprising of PD patients and their caregivers in two independent centers in America and Asia, the level of knowledge about genetic testing and patients' attitudes towards such testing were evaluated using a standardized questionnaire. RESULTS: American PD patients had a higher level of knowledge of PD genetics than Asian PD (31.1% vs. 12.3%, p=0.0002). A greater number of American PD patients and caregivers reported a positive attitude towards the potential medical benefits of genetic testing compared to their Asian counterparts (85.4% vs. 42.2%, 92.2% vs. 32.1%, p<0.00005), but a more negative attitude towards potential compromise in getting health and life insurance (43.7% vs. 25.8%, p=0.0002). However, in the Asian cohort, multivariate analysis revealed that a high level of genetics knowledge was associated with a positive attitude response regarding the potential medical benefits of testing (p<0.0005), but a negative attitude towards compromises in healthcare and life insurance, getting a job and starting a family (p<0.0005). These associations were not observed amongst American subjects. CONCLUSIONS: The relationship between level of genetic knowledge and attitude towards potential risks and benefits of predictive genetic testing in PD was distinctly different in two independent, racially and culturally different PD populations and caregivers. These observations have clinical implications in the development of PD genetic counseling programs.

Adult↗
PubMed2006

The LRRK2 Gly2385Arg variant is associated with Parkinson's disease: genetic and functional evidence.

Evidence of LRRK2 haplotypes associated with Parkinson's disease (PD) risk was recently found in the Chinese population from Singapore, and a common LRRK2 missense variant, Gly2385Arg, was independently detected as a putative risk factor for PD in the Chinese population from Taiwan. To test the association between the Gly2385Arg variant in a large case-control sample of Chinese ethnicity from Singapore, and to perform functional studies of the wild type and Gly2385Arg LRRK2 protein in human cell lines. In a case-control study involving 989 Chinese subjects, the frequency of the heterozygous Gly2385Arg genotype was higher in PD compared to controls (7.3 vs. 3.6%, odds ratio = 2.1, 95% CI: 1.1-3.9, P = 0.014); these values yield an estimated population attributable risk (PAR) of approximately 4%. In a multivariate logistic regression analysis with the disease group (PD vs. controls) as the dependent variable and the genotype as an independent factor with adjustments made for the effect of age and gender, the heterozygous Gly2385Arg genotype remained associated with an increased risk of PD compared to wild type genotype (odds ratio = 2.67, 95% CI: 1.43-4.99, P = 0.002). The glycine at position 2385 is a candidate site for N-myristoylation, and the Gly2385Arg variant replaces the hydrophobic glycine with the hydrophilic arginine, and increases the net positive charge of the LRRK2 WD40 domain. In transfection studies, we demonstrated that both the wild type and Gly2385Arg variant LRRK2 protein localize to the cytoplasm and form aggregates. However, under condition of oxidative stress, the Gly2385Arg variant was more toxic and associated with a higher rate of apoptosis. Our study lends support to the contention that the Gly2385Arg is a common risk factor for PD in the Chinese population. Our bioinformatics and in-vitro studies also suggest that the Gly2385Arg variant is biologically relevant and it might act through pro-apoptotic mechanisms.

Aged↗
PubMed2006

Intraoperative monitoring study of ipsilateral motor evoked potentials in scoliosis surgery.

Ipsilateral motor evoked potentials (MEPs) in spinal cord surgery intraoperative monitoring is not well studied. We show that ipsilateral MEPs have significantly larger amplitudes and were elicited with lower stimulation intensities than contralateral MEPs. The possible underlying mechanisms are discussed based on current knowledge of corticospinal pathways. Ipsilateral MEPs may provide additional information on the integrity of descending motor tracts during spinal surgery monitoring.

Adolescent↗
PubMed2006

Transcranial magnetic stimulation screening for cord compression in cervical spondylosis.

OBJECTIVE: Cervical spondylosis (CS) often results in various degrees of cord compression, which can be evaluated functionally with transcranial magnetic stimulation (TMS). We investigate the use of TMS as a screening tool for myelopathy in CS. METHODS: We prospectively studied 231 patients classified into Groups 1 to 4 based on MRI grading of severity of cord compromise. TMS elicited central motor conduction times and motor evoked potential (MEP) amplitudes in all 4 limbs. The results were compared with those from 45 healthy controls. RESULTS: TMS showed 98% sensitivity and 98% specificity for cord abnormality using MRI as reference standard. CONCLUSIONS: MEP abnormalities are useful for electrophysiological evaluation of cord compression in CS. While TMS is not a substitute for MRI, it is of value as a rapid, inexpensive and non-invasive technique for screening patients before MRI studies.

Adult↗
PubMed2006

Magnetic brainstem stimulation of the hypoglossal nerve in normal subjects.

Electrophysiological evaluation of motor pathways to the lingual muscles is technically challenging. Previous studies utilizing transcranial magnetic stimulation (TMS) of the parieto-occipital region with a round coil reported difficulties in eliciting tongue motor responses. In this study, we utilized TMS with a double cone coil at the posterior head region to obtain tongue motor evoked potentials. Our findings suggest activation at or distal to the hypoglossal nuclear level, but proximal to the hypoglossal canal region. Our method can be usefully applied in future studies of brainstem and cranial nerve function.

Adult↗
PubMed2006

Effectiveness of 3-in-1 continuous femoral block of differing concentrations compared to patient controlled intravenous morphine for post total knee arthroplasty analgesia and knee rehabilitation.

We assessed the effectiveness of the 3-in-1 continuous femoral block as a form of postoperative pain relief for unilateral total knee arthroplasty (TKA). Sixty patients undergoing elective unilateral TKA under subarachnoid block were randomized into three groups. Postoperative analgesia was provided with a continuous 3-in-1 femoral nerve catheter with 0.15% ropivacaine in group A, a continuous 3-in-1 femoral nerve catheter with 0.2% ropivacaine in group B, or patient controlled intravenous morphine in group C (control group). Groups A and B received patient controlled intravenous morphine pumps for rescue analgesia. Patients in each group were followed for 72 hours postoperatively. Five patients were excluded after randomization. In the remaining 55 patients there was no statistical difference in pain score between the groups. Total morphine use was highest in group C (P < 0.05). No appreciable difference could be found with sensorimotor blockade, morphine usage and satisfaction scores when comparing groups A and B. Femoral catheter dislodgement rate was 7.9%. There was no statistical difference between the groups when comparing the day of first ambulation and the time to discharge from the hospital. Satisfaction scores were higher in group A (P = 0.028) and group B (P = 0.002) compared to group C. We conclude that a continuous 3-in-1 femoral nerve block with ropivacaine 0.15% or 0.2% for elective unilateral TKA has an opioid-sparing effect.

Age Factors↗
PubMed2005

Ventrolateral medullary compression in hypertensive patients with hemifacial spasm.

In a patient-controlled study, the authors demonstrated a significantly higher prevalence of rostral ventrolateral medulla (VLM) compression in hypertensive patients with hemifacial spasm (HFS) compared with age-, sex-, race-, disease duration-, and disease severity-matched normotensive patients with HFS (p = 0.02). Hypertensive HFS patients were more likely to have a greater severity of neurovascular compression at the VLM compared with normotensive HFS patients (p = 0.008). VLM compression is associated with risk of hypertension in this study population.

Adult↗
PubMed2005

Impaired transcriptional upregulation of Parkin promoter variant under oxidative stress and proteasomal inhibition: clinical association.

We provided data to show that the transcriptional activity of wildtype -258T in the parkin promoter region was significantly higher than the -258G variant in human cell lines. The transcriptional activity of wildtype -258T was significantly increased under oxidative stress by hydrogen peroxide, but this was not observed for the -258G variant. The transcriptional upregulation was significantly higher for wildtype -258T compared to -258G variant at 0.1, 0.2 and 0.4 mM of hydrogen peroxide. Similar results were obtained when the cells were treated with a proteasome inhibitor, MG132.Furthermore, in a case control study involving 753 subjects, we demonstrated that the parkin promoter -258G variant was associated with an increased risk of sporadic Parkinson's disease (PD) in the elderly ethnic Chinese population. Our clinical and laboratory data provide corroborative evidence that some older individuals who have the -258G variant may have a higher risk of developing PD.

Age Factors↗
PubMed2005

Differential expression of splice variant and wild-type parkin in sporadic Parkinson's disease.

BACKGROUND: Altered splicing of parkin under cellular stress could lead to changes in gene expression and altered protein activity. The causative role of parkin in sporadic Parkinson's disease (PD) is unknown. OBJECTIVES: We described a parkin splice variant (SV) in the substantia nigra and leukocytes of sporadic PD patients. Using a case control methodology, we investigated the exon 4 SV (E4SV) and wild-type parkin expression in the leukocytes of sporadic PD patients and healthy individuals. METHODS/RESULTS: We identified a parkin E4SV in the substantia nigra and leukocytes of sporadic PD patients and controls by reverse transcriptase-polymerase chain reaction (PCR). The exon 4 (122 bp) deletion resulted in a reading frame shift over the junction of exons 3-5 and a stop codon (tga) 17 bp downstream from exon 3. The translated truncated protein was associated with a total loss of the two-RING finger functional domain. Utilizing TaqMan real-time PCR with probes located across the junction of exons 3-4 or 3-5, we demonstrated an over-expression of E4SV/wild-type parkin ratio in the leukocytes of sporadic PD patients compared to age-, gender-, and race-matched controls (p<0.0005). A multivariate regression analysis demonstrated that the ratio of E4SV/wild-type parkin expression increased with age in PD patients, but this was not observed in the controls (p<0.0005). CONCLUSION: The relative expression of E4SV/wild type parkin was increased in sporadic PD compared to healthy controls. Based on our observations, further functional studies to determine the pathophysiologic role of E4SV in sporadic PD patients will be of importance.

Aged↗
PubMed2005

Reflex vasoconstrictor responses of the healthy human fingertip skin. Normal range, repeatability, and influencing factors.

Skin vasoconstrictor reflexes (SVCRs) are mediated by sympathetic vasoconstrictor nerve fibers and used to test sympathetic function of the extremities. Since there is a dearth of published systematic data on inspiratory gasp-induced SVCR, we studied its range, repeatability, and influencing factors in 64 healthy subjects (mean age 41.9 years, range 20-78 years, 32 males). Mean vasoconstriction for the second digit was 54% (+/-19)/54% (+/-19) (right/left) and 69% (+/-16)/68% (+/-15) for the fourth digit. Forth digit vasoconstriction was significantly larger than the second digit (P < 0.01), but second and fourth digit correlation was good (Pearson: 0.521-0.741). Repeatability using single measure intraclass correlation was good with 0.62/0.69 for the second digit and 0.64/0.80 for the fourth digit (right/left). A trend for decreasing SVCR was seen with increasing age and weight, no effect was seen for gender, height, or blood pressure. The SVCR repeatability and range of variation seen in this study compare favorably with tests of heart rate variability, thermal threshold detection, and motor nerve conduction.

Adult↗
PubMed2005

Behind the facial twitch: depressive symptoms in hemifacial spasm.

BACKGROUND: Depression impairs psychosocial and occupational functioning and contributes to significant morbidity and mortality. Hemifacial spasm (HFS) causes social embarrassment and visual and verbal disability. OBJECTIVE: We examined; (1) the prevalence and predictive factors of depressive symptoms (Becks Depression Inventory (BDI) and clinical assessment) in HFS and (2) the sensitivity and specificity of BDI as a screening and diagnostic tool in HFS. METHODS: A large cohort of HFS patients in a movement disorders clinic was clinically evaluated and the BDI self-administered by patients. Univariate analysis and multivariate logistic regression were undertaken to investigate the effect of age, gender, body-mass index, duration and severity of HFS on the outcome of BDI score. ROC (receiver operating characteristics) analysis was utilized to evaluate the sensitivity and specificity and discriminative property of the scale. RESULTS: There were 90 HFS patients with a mean age of 54.4+11.1 (35-79) years, comprising of 58.9% women and with a mean severity HFS score of 2.9+0.8 (range 1-4). The mean BDI score was higher in depressed HFS than in non-depressed HFS (19.7+6.7 vs 4.2+4.9, p<0.0001). Female gender and a younger age were risk factors (p=0.07). In the multivariate analysis, the severity of HFS was an independent predictor of BDI scores (p<0.0001). The AUC was 97.1% suggesting excellent discriminative property of BDI. For cut-off score of 12/13, the sensitivity was 93.3%, specificity 94.7%, Positive Predictive Value 77.8% and Negative Predictive Value 98.6%. CONCLUSIONS: The prevalence of depressive disorder in HFS was 16.7%, with younger women at greater risk. The severity of HFS was positively correlated with the severity of depressive symptoms. The BDI can be a complimentary screening and/or diagnostic instrument for depressive disorder in HFS. Early diagnosis of at-risk patients will prevent unnecessary morbidity and mortality.

Adult↗
PubMed2005

Non-motor manifestations in essential tremor: use of a validated instrument to evaluate a wide spectrum of symptoms.

INTRODUCTION: Recent studies suggest an association between non-motor symptoms and essential tremor (ET). Few studies have assessed psychological symptoms in ET. These studies were limited to western white populations and utilized scales that were specific to only one or two psychiatric domains. By contrast, the Symptom Checklist-90R (SCL-90R) is a validated clinical scale to screen for symptoms related to a spectrum of nine different psychological domains. OBJECTIVE: To determine whether a wide spectrum of non-motor manifestations is associated with ET in patients in an Asian cohort. METHODS: Consecutive ET patients and a group of control subjects were evaluated using the SCL-90R, which is comprised of items in nine major symptom dimensions and three global indices, including the positive symptom distress index. RESULTS: ET patients (N = 84) and controls (N = 78) were similar in age (50.0+/-18.0 vs 46.0+/-14.4 years), gender and other demographic variables. ET patients had higher scores in three of nine major symptom dimensions: anxiety, phobic anxiety (p < 0.0005) and psychoticism (p = 0.005). In multivariate analysis, the anxiety (p < 0.0005) and the positive symptom distress index scores (p < 0.0005) were greater in ET patients compared to controls after adjusting for sex, age, marital status and educational level. The severity, but not duration of ET was correlated with the severity of anxiety symptoms. CONCLUSIONS: Utilizing the SCL-90R, we highlighted that ET patients reported more non-motor symptoms than healthy controls. The more frequent occurrence of anxiety symptoms in our Asian cohort extends the observation that such non-motor manifestations should be considered in the clinical management of ET.

Adult↗
PubMed2005

Validation of a short disease specific quality of life scale for hemifacial spasm: correlation with SF-36.

BACKGROUND: A short, practical, and validated quality of life (QoL) scale for hemifacial spasm (HFS) is not currently available. OBJECTIVES: To examine the reliability and validity of a short self-rating scale (HFS-7) by comparing HFS patients with healthy controls. We also evaluated the correlation of HFS-7 with the physical and mental domains of SF-36, a generic QoL scale. METHODS: Seven self-rating items (HFS-7) were administered to HFS patients and healthy controls. In addition, HFS patients answered the SF-36 questionnaire. The validity and reliability of HFS-7 were analysed and correlation between HFS-7 and SF-36 examined. RESULTS: A total of 178 subjects were enrolled in the study, including 85 HFS patients with mean age of 54.8 (SD 11.0) years, of whom 52 (61.2%) were women, and 93 controls with mean age of 51.4 (SD 10.0) years, of whom 59 (63.4%) were women. The test-retest intraclass correlation coefficient for the seven items was between 0.75 and 0.90 and Cronbach's coefficient of reliability for the HFS-7 scale was 0.88. Every item in HFS-7 discriminated between disease and controls (p<0.0001). The HFS-7 summary index correlated with the SF-36 summary score (Spearman's correlation r = -0.28, p = 0.009), in particular the mental health summary score (r = -0.416, p<0.0001) and the emotional domain (r = -0.466, p<0.00001). CONCLUSION: HFS-7 could prove useful as a simple clinical tool to assess and monitor QoL measures in HFS patients.

Adult↗
PubMed2004

A transcranial magnetic stimulation study of the ipsilateral silent period in lower limb muscles.

The lower limb ipsilateral silent periods (ISP) were determined with transcranial magnetic stimulation in 30 normal subjects using a round coil. The mean duration and transcallosal conduction time were comparable to values obtained from upper limb recordings. No age-related correlation was found for either parameter, corroborating previous imaging and pathological studies of interhemispheric pathways. Our results highlight the feasibilty of eliciting ISPs in the lower limbs, relevant for future studies of interhemispheric interaction in clinical and research settings.

Adult↗
PubMed2004

Ipsilateral and contralateral motor inhibitory control in musical and vocalization tasks.

The inhibitory motor control mechanisms in human singing and vocalization are not well understood. Using transcranial magnetic stimulation (TMS), we show that singing resulted in right-sided prolongation of ipsilateral silent period and bilateral reduction in contralateral silent period. Reading led to reduced contralateral silent period duration with right-sided TMS only, but no significant inhibitory changes, both ipsilateral and contralateral, were evident with humming. The findings support the presence of enhanced interhemispheric inhibitory motor interaction during singing, as opposed to reading tasks, in dynamic word generation coupled with production of melody.

Adult↗
PubMed2004

Systematic correlation of transcranial magnetic stimulation and magnetic resonance imaging in cervical spondylotic myelopathy.

STUDY DESIGN: A prospective study over a 3.5-year period involving transcranial magnetic stimulation and magnetic resonance imaging. OBJECTIVES: To assess the correlation of transcranial magnetic stimulation and magnetic resonance imaging in cervical spondylotic myelopathy qualitatively and statistically. SUMMARY OF BACKGROUND DATA: Cervical spondylotic myelopathy presents with different degrees of cord compression, which can be assessed by magnetic resonance imaging. There are no large studies correlating transcranial magnetic stimulation and magnetic resonance imaging findings in this condition. METHODS: A total of 141 patients with a clinical diagnosis of cervical spondylotic myelopathy were prospectively studied over a 3.5-year period. They were classified into Groups 1 to 4 based on severity of cervical cord changes on magnetic resonance imaging. All had transcranial magnetic stimulation and central motor conduction time measurements within 2 months of the magnetic resonance imaging study. RESULTS: Twenty-eight, 49, 28, and 36 patients were classified into Groups 1 to 4, respectively. Mean upper limb and lower limb central motor conduction times correlated with the severity of magnetic resonance cord compression. The absence of central motor conduction time abnormalities correlated reliably with the absence of cervical cord impingement as in Group 1. Statistically significant right left difference in central motor conduction time in the lower limbs was seen between Groups 1 (no cord changes) and Group 2 (mild cord impingement). Eight other patients with diagnoses other than cervical spondylotic myelopathy all showed central motor conduction time abnormalities. The sensitivity and specificity for transcranial magnetic stimulation for differentiating the presence from absence of magnetic resonance imaging cord abnormality were 100% and 84.8%, respectively. CONCLUSIONS: Transcranial magnetic stimulation showed excellent correlation with magnetic resonance imaging findings and can be considered as an effective technique for screening patients for cervical cord abnormalities before magnetic resonance imaging in the clinical setting. The findings in this study have relevant implications in the pathophysiology, management, and health costs of cervical spondylotic myelopathy.

Adult↗