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Biomedical subjects

S B Tan

Publications and source records attributed to S B Tan.

At least 19 recordsLinked to original sources

Biometrical aspects of drug development.

Once the activity of a compound has been established in the laboratory (usually by use of experimental animals) the next stage of development is to bring this forward to humans in early-phase clinical trials. A pharmacokinetic study aims to establish an effective dosing regimen for the compound in order to reach concentrations within the therapeutic window as quickly as possible. The aim of the phase I trials is typically to determine a maximal safe dose with which more rigorous investigation of activity in a phase II trial can be conducted. This chapter deals with statistical issues related to the design of phase I studies.

Animals↗

Congenital osteofibrous dysplasia associated with pseudoarthrosis of the tibia and fibula.

The association between congenital pseudoarthrosis and osteofibrous dysplasia of the tibia and fibula is a rare entity that has been recently recognized. We report a male newborn who was found to have swelling and deformity of the left lower leg. Radiographs and magnetic resonance imaging showed an extensive destructive lesion of the tibial shaft, with dysplastic congenital pseudoarthrosis of the lower fibula. Histopathological examination confirmed the diagnosis of congenital pseudoarthrosis of the tibia and fibula with underlying osteofibrous dysplasia involving both bones. Immunohistochemical stains showed cytokeratin positivity.

Fibrous Dysplasia of Bone↗

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↗

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↗

Pectoralis major motor evoked potentials in cervical spondylosis.

Myelopathy is a severe complication of cervical spondylosis (CS). We studied 27 consecutive patients with CS referred for evaluation for possible myelopathy using transcranial magnetic stimulation. The findings were compared with those from 20 normal controls. Magnetic resonance imaging was utilized to assess the degree of cord compromise. Central motor conduction time (CMCT) abnormalities showed equivalent diagnostic yield with pectoralis major (PM) recordings, as compared with combined first dorsal interossei and abductor hallucis recordings. Our findings show that CMCT measurement with PM recordings is of value as a diagnostic adjunct in the electrophysiological evaluation of myelopathy in CS.

Adult↗

Candida spondylodiscitis and epidural abscess: management with shorter courses of anti-fungal therapy in combination with surgical debridement.

Epidural abscess associated with candidal spondylodiscitis is rarely seen, particularly when it involves the cervical and thoracic spine. We report two such cases that were successfully managed with early surgical debridement, as well as medical therapy with intravenous amphotericin followed by oral fluconazole. The literature related to candidal spinal infection is reviewed, and a rational approach to the management of this uncommon condition is proposed. A good outcome may generally be expected with early diagnosis as well as appropriate surgical and pharmacological treatment. Oral fluconazole appears to be useful in the management of candida spondylodiscitis complicated by epidural abscess formation. Treatment until a normal ESR is attained is ideal, and this may be as short as 3 months when surgical drainage has been adequately performed.

Antifungal Agents↗

Risk perception is affected by modes of risk presentation among Singaporeans.

INTRODUCTION: Not much is known about how Singaporeans perceive and react to risk presentation. There is no consensus on whether the European Union guidelines for describing the risk of side effects are valid. This study investigated the effect of different modes of risk presentation on how Singaporeans perceive and react to medical risk. Furthermore, we investigated the practical usage of qualitative phrases, the European Union's adjectives in particular, in describing levels of risk. MATERIALS AND METHODS: A hypothetical situation about the risk of side effects of an influenza vaccine was presented in either a probability format (i.e., 5%; n = 42) or a frequency format (i.e., 1 out of 20; n = 43). The 2 versions of questionnaire were handed out in an alternate order to a convenience sample of 47 healthcare professionals and 38 university students. RESULTS: Respondents presented with a "5% risk" were more likely to describe the risk as "uncommon" or "rare", as compared to respondents presented with a risk of "one out of twenty" (P <0.01). Furthermore, the former showed more willingness to accept the influenza vaccine described in the hypothetical situation than in the latter, but this was not statistically different (67% versus 54%; P >0.1). CONCLUSIONS: Modes of risk presentation affect how people perceive risk, even among people who are highly educated.

Adult↗

p53 and bcl-2 expression in invasive and pre-invasive uterine papillary serous carcinoma and atrophic endometrium.

INTRODUCTION: Uterine papillary serous carcinoma (UPSC), a high-grade tumour, is known to be associated in some cases with an identifiable intraepithelial neoplasia (IEN) component. Biomarker studies incorporating this latter component are not well documented. One aim of the present study was to compare levels of immunohistochemical (IHC) expression of p53 tumour suppressor gene and bcl-2 oncoprotein between UPSC and IEN, as well as normal endometrium to determine its biologic significance. The other major aim was to determine if these IHC results have any bearing on survival data in this tumour. MATERIALS AND METHODS: An immunoreactivity score was assigned for examination of p53 and bcl-2 expression in a total of 21 cases of UPSC, 9 with an evaluable IEN component and 11 with associated non-neoplastic endometrium. Statistical analysis of IHC results was performed, in addition to correlation with survival data and disease stage. RESULTS: p53 was identified in 16/21 cases of UPSC (76%) and 8/9 cases of IEN (89%), and no cases of normal endometrium. By contrast, bcl-2 was positive in all normal endometria with less expression in UPSC leaving 15/21 (71%) cases positive, and in IEN, leaving 5/9 (55%) of cases positive. Differences in immunoreactive scores for both p53 and bcl-2 between UPSC and benign glands, as well as between IEN and benign glands reached statistical significance with P values of 0.006 and 0.014 for p53, and 0.003 and 0.027 for bcl-2 respectively. There was no statistical significance between values for UPSC and IEN. Cox regression analysis found no statistically significant relationship between patient survival time in early and late stages of disease, and p53 and bcl-2 immunoscores. CONCLUSIONS: The lack of a significant difference between the bcl-2 and p53 values for both UPSC and IEN suggests that these molecular alterations occur at an early stage of tumour pathogenesis. A potential advantage of the use of immunohistochemical markers is their application to routinely processed surgical specimens. In this case, bcl-2 and p53 were applied in UPSC to determine any potential significance, but neither marker proved to be a useful predictor of survival time or disease stage.

Atrophy↗

Determination of the flight range and dispersal of the house fly, Musca domestica (L.) using mark release recapture technique.

In order to control any pest it is essential to study the life cycle, biology and bionomics of the target pest under control. With this respect, we have studied the flight range of the house fly Musca domestica (L.). The flight range of the house fly from two sites i.e, the poultry farm and a stable farm has been studied. The flight range study was conducted using a mark release technique. The approach we used in this study was that the flies collected from the respective farms were marked and released at different distances from the farms. The flies were then re-captured from the poultry farm and the stable farm. Studies conducted elsewhere use the technique of releasing the insect species at one spot and recapturing the insect species with the help of baited traps placed at various locations from the release point. The advantage of the approach used in this study was that the flight range as well as the homing effect was determined. From this study, the flight range of house flies released at the poultry farm was 7 km whereas flight range for flies release from stable farm was 5 km. The recovery rate of house flies at the poultry and stable farm was 0.05% and 0.016%, In this study, marked specimens has been detected up to 8 days in field conditions indicating that under field condition the life expectancy could be in the range of 1-2 weeks.

Agriculture↗

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↗

Intra-operative monitoring in scoliosis surgery with multi-pulse cortical stimuli and desflurane anesthesia.

STUDY DESIGN: Prospective, observational study. SETTING: Country General Hospital, Singapore. OBJECTIVE: Intraoperative monitoring (IOM) with motor-evoked potentials (MEPs) assesses the integrity of cortical spinal tracts during scoliosis surgery. MEPs are sensitive to the effects of inhalational anesthetic agents. We evaluate the use of desflurane in combination with multipulse cortical stimulation in this study. METHODS: In all, 10 consecutive neurologically normal subjects underwent scoliosis surgery with desflurane anesthesia (0.5 maximum alveolar concentration) and five pulse cortical stimulation (250 Hz) from two stimulators in parallel configuration, delivering a maximum intensity of 160 mA. RESULTS: Consistent MEPs were obtained from the abductor hallucis and tibialis anterior in nine of ten and five of five of subjects, respectively. Baseline coefficients of variations were below 16% for both muscles. CONCLUSION: This combination of anesthetic and stimulation protocols is efficacious for IOM during spinal cord surgery. Our findings support the use of desflurane for successful acquisition of MEPs during scoliois surgery as an alternative anesthetic regime.

Adolescent↗

Nonrandom intragenic variations in patterns of codon bias implicate a sequential interplay between transitional genetic drift and functional amino acid selection.

Although most codon third bases appear to be functionless, the synonymous codons so defined exhibit a strikingly nonrandom distribution (codon bias) within human and other genes. To examine this phenomenon further, we generated a database of DNA sequences encoding human transmembrane cell-surface receptor proteins. Using this database we show here that the guanine and cytosine content of codon third bases (GC3) varies intragenically with the nature of the specified receptor domains (transmembrane > extracellular > intracellular domains; p < 0.001), the phenotype of the encoded amino acids (hydrophobic > hydrophilic > neutral amino acids; p < 0.001), and the receptor affiliation of the transmembrane (G-protein-coupled receptors > receptor tyrosine kinases; p < 0.001). Within gene regions specifying transmembrane domains, GC3 declines as domain functionality becomes redundant with increasing hydrophobicity (p < 0.001). Codons containing the second-base cytosine (XCZ, which encodes neutral amino acids) are selectively depleted of third-base adenine content (A3: XCA codons) when encoding transmembrane domain residues, consistent with positive selection for transitional mutation of XCG to XTG (which encodes hydrophobic amino acids) rather than to the synonymous XCA. Supporting this XCG --> XTG mechanism of codon bias, the G3:A3 ratio of codons specifying the transmembrane amino acid glycine (GGZ) is intermediate between that of its functional homolog alanine (GCZ) and that of hydrophobic valine (GTZ), even though the C3:T3 ratios are similar. Conversely, nearest-neighbor analysis of third bases 5' to codons specifying valine and leucine (CTZ) confirms a significant difference in C3:T3 but not G3:A3 ratios (i.e., C3/G1 --> T3/G1 > C3/A1; p < 0.001), consistent with the functionally advantageous retention of hydrophobic residues. These data raise the possibility that patterns of intragenic codon bias reflect a balance between negative and positive selection, suggesting in turn that analysis of codon third-base usage may help to predict the functional significance of encoded products.

Amino Acids↗

Measuring quality of life in Chinese cancer patients: a new version of the Functional Living Index for Cancer (Chinese).

INTRODUCTION: Since its translation into Chinese, the Functional Living Index for Cancer (FLIC) has not been widely received due to some of its difficulties. We modified its visual analogue scale (VAS) to an ordered categorical scale and changed some of the wording in the instrument. This study examined the measurement properties of the modified FLIC. MATERIALS AND METHODS: The modified version of FLIC and the Functional Assessment of Cancer Therapy (FACT-G Chinese version 4) were filled in by 140 patients recruited from the National Cancer Centre Singapore. The patients' FLIC scores were compared with their clinical characteristics to establish known-group validity. Convergent and divergent validity of FLIC were examined by correlation analysis with FACT-G and its sub-scales. Cronbach's alpha and relative efficiency were also examined. RESULTS: FLIC and most of its sub-scales could indicate a clear and statistically significant difference of quality of life (QOL) according to patients' performance status and treatment status. FLIC strongly correlated with FACT-G. The Physical, Psychological, and Symptoms sub-scales of FLIC converged to and diverged from FACT-G sub-scales as conceptually expected. Cronbach's alpha indicated a satisfactory level of reliability. FLIC appeared to be more efficient than FACT-G, meaning that a smaller sample size will be required for FLIC than for FACT-G to achieve the same research purpose. CONCLUSIONS: The modified version of FLIC was found to have achieved satisfactory measurement properties. This is a user-friendly alternative to the original FLIC.

China↗

A 16-year-old boy with back pain.

This case is presented to illustrate the imaging and clinical findings of a condition of interest to orthopaedic surgeons. The initial findings are noted on this page. The clinical and imaging diagnoses are presented on the following pages.

Adolescent↗