1.Pharmacogenomics In Drug Therapy And Interaction: The Role Of Cytochrome P450
Chin-Eng Ong ; Yan Pan ; Kai-Hung Tiong ; Beow-Chin Yiap ; Eng-Lai Tan ; Peter Pook ; Joon-Wah Mak
International e-Journal of Science, Medicine and Education 2008;2(supp1):6-10
Pharmacogenomics (or pharmacogenetics),
the study of the effects of genetic differences on a
person’s response to drugs, can help in optimizing drug
efficacy and minimizing adverse drug reactions.
Interperson difference in drug metabolism is one of the
important consequences of such genetic variation. This
variation is determined in part by mutations in
cytochrome P450 enzymes (CYPs). IMU is part of a
major collaborative research project in the area of
phamacogenetics and drug metabolism. Working
together with USM and UiTM, our group has, since
2000, generated useful population database on genetic
polymorphism of various CYP isoforms. We have
successfully genotyped three major ethnic groups,
Malay, Indian and Chinese for their allelic frequency of
important isoforms. These include CYP2D6, CYP2C9,
CYP2C8 and CYP2A6. Data generated so far
collectively have contributed to our effort in mapping
and constructing genomic database for Malaysian
population.
Since early 2002, our research has been focusing on
developing in vitro methods in studying the functional
consequences of genetic polymorphism of CYP enzymes.
Using site-directed mutagenesis, CYP mutants, carrying
nucleotide changes as reported in known alleles in
human populations, were generated and expressed in
E. coli system, and the expressed recombinant proteins
were characterized using enzyme assays to determine
the functional consequences of mutations. We have
established a series of HPLC (high performance liquid
chromatography)-based and fluorescence-based assays
to investigate CYP activities. Assays that have been
developed include tolbutamide methylhydroxylase,
paclitaxel 6a-hydroxylase, dextromethorphan
O-demethylation, testosterone 6b-hydroxylation and
coumarin 7-hydroxylase assays. These assays serve as
activity markers allowing comparison of catalytic
activities of mutant proteins generated. Another focus
of our work is to use the developed assays as a screening
tool to investigate drug-herb interactions. This was
achieved by co-incubation of herbal extracts and active
constituents with the probe substrates in the assays followed by characterization of the kinetic behaviors of
the enzymes involved using various pharmacokinetic
parameters such as Km, Vmax, IC50 and Ki. This work is
currently carried out with collaboration from the
Institute for Medical Research (IMR) and is supported
by MOSTI’s eScienceFund under RM9. It is envisaged
that this screening work will give us insights on the
potential of the commonly used herbs to cause
pharmacokinetic interactions with other drug
substrates, and allow us to elucidate the mechanisms
involved in the interactions.
2.Bioactive molecules: current trends in discovery, synthesis, delivery and testing
Yew Beng Kang ; Pichika R Mallikarjuna ; Davamani A Fabian ; Adinarayana Gorajana ; Chooi Ling Lim ; Eng Lai Tan
International e-Journal of Science, Medicine and Education 2013;7(supp1):S32-46
Important bioactive molecules are molecules
that are pharmacologically active derived from natural
sources and through chemical synthesis. Over the years
many of such molecules have been discovered through
bioprospective endeavours. The discovery of taxol from
the pacific yew tree bark that has the ability in stabilising
cellular microtubules represents one of the hallmarks of
success of such endeavours. In recent years, the discovery
process has been aided by the rapid development
of techniques and technologies in chemistry and
biotechnology. The progress in advanced genetics and
computational biology has also transformed the way
hypotheses are formulated as well as the strategies for drug
discovery. Of equal importance is the use of advanced
drug delivery vehicles in enhancing the efficacy and
bioavailability of bioactive molecules. The availability of
suitable animal models for testing and validation is yet
another major determinant in increasing the prospect for
clinical trials of bioactive molecules.
3.A Practical Guide to Ordering and Interpreting Coagulation Tests for Patients on Direct Oral Anticoagulants in Singapore.
Wan Hui WONG ; Christina Yc YIP ; Christina Ll SUM ; Chuen Wen TAN ; Lai Heng LEE ; Eng Soo YAP ; Ponnudurai KUPERAN ; Wen Chang TING ; Heng Joo NG
Annals of the Academy of Medicine, Singapore 2016;45(3):98-105
INTRODUCTIONDirect oral anticoagulants (DOACs) are establishing themselves as principle choices for the treatment of a variety of thrombotic disorders. DOACs are also known to affect common coagulation tests which are routinely performed for patients in clinical practice. An understanding of their varied effects is crucial for the appropriate ordering of coagulation tests and their interpretation.
MATERIALS AND METHODSLaboratories in public and private healthcare institutions and commercial sectors were surveyed on coagulation tests offered and their methods. A Medline and bibliography search, including a search on search engines, was performed for publications reporting the effects of dabigatran, apixaban and rivaroxaban on these coagulation tests. These papers were reviewed and summarised for consensus recommendations.
RESULTSProthrombin time (PT) and activated partial thromboplastin time (aPTT) are variably affected by the DOACs and dependent of the coagulation assays used. Clinicians must know which laboratory has performed these tests to logically interpret test results. A normal PT or aPTT does not exclude the presence of residual DOACs effect. The thrombin time is sensitive to dabigatran but not apixaban or rivaroxaban. Specialised coagulation tests such as thrombophilia tests are also variably affected by the DOACs. All laboratories in Singapore however, employ similar test methods permitting a common set of recommendations for specialised coagulation testing.
CONCLUSIONKnowledge of the effects of DOACs on coagulation testing is essential to determine the appropriateness of performing such tests and interpreting them coherently. Practical recommendations which are tests and location-specific are set out in this paper.
Antithrombins ; therapeutic use ; Blood Coagulation Tests ; Dabigatran ; therapeutic use ; Factor Xa Inhibitors ; therapeutic use ; Humans ; Partial Thromboplastin Time ; Practice Guidelines as Topic ; Prothrombin Time ; Pyrazoles ; therapeutic use ; Pyridones ; therapeutic use ; Rivaroxaban ; therapeutic use ; Singapore
4.Bone marrow cytogenetics workup: Application of lean management system to determine if additional cell workup is helpful and necessary to analysis.
Alvin S T LIM ; Ting Jie CHEN ; Tse Hui LIM ; Mary TAN ; Lai Ching LAU ; Ping LIM ; Geok Yee LEE ; Li Eng LOO ; Fiona P S LIAW ; Charles T H CHUAH ; Yeow Tee GOH ; Sim Leng TIEN
Annals of the Academy of Medicine, Singapore 2010;39(9):696-699
INTRODUCTIONHigh workload volumes in a Cytogenetics laboratory can lead to long result turn-around times (TAT). This study aimed to improve laboratory efficiency by adopting Lean Management System initiatives to increase productivity through the elimination of wastes. This study examined if the prerequisite 20-cell analysis was sufficient for a conclusive result or if additional cell workup was necessary to ascertain the presence of a previous chromosome abnormality among cases on follow-up, or when a single abnormal cell was encountered during the analysis to determine the presence of a clone.
MATERIALS AND METHODSThe karyotype results of cases that had additional workup were retrieved from among 8040 bone marrow cases of various haematological disorders performed between June 2003 and June 2008.
RESULTSOf 8040 cases analysed, 2915 cases (36.3%) had additional cell workup. Only 49 cases (1.7%) led to the establishment of a clone. The majority of these cases could have been resolved without the additional workup, especially if fluorescence in situ hybridization (FISH) or polymerase chain reaction (PCR)-based assays had been utilised.
CONCLUSIONThis study shows that the additional workup procedure is redundant. The time saved by discontinuing the workup procedure can be used to analyse other cases, leading to increased laboratory efficiency and a faster TAT without compromise to patient care. The practice of additional workup over and above the 20- cell analysis should be dispensed with as little benefit was derived for the amount of additional manpower expended. FISH or PCR-based assays should be utilised to elucidate a case further.
Adult ; Aged ; Aged, 80 and over ; Bone Marrow ; Bone Marrow Cells ; Cytogenetics ; Efficiency ; Efficiency, Organizational ; Female ; Hematologic Diseases ; diagnosis ; pathology ; Humans ; In Situ Hybridization, Fluorescence ; instrumentation ; methods ; Karyotyping ; instrumentation ; methods ; Male ; Polymerase Chain Reaction
5.Endoscopic submucosal dissection of colorectal neoplasms: an audit of its safety and efficacy in a single tertiary centre in Singapore.
James Weiquan LI ; Tiing Leong ANG ; Lai Mun WANG ; Andrew Boon Eu KWEK ; Malcolm Teck Kiang TAN ; Kwong Ming FOCK ; Eng Kiong TEO
Singapore medical journal 2019;60(10):526-531
INTRODUCTION:
Endoscopic submucosal dissection (ESD) provides a higher en bloc and R0 resection rate than endoscopic mucosal resection. Colorectal ESD is not widely used because of its technical difficulty and risk of complications, especially for right-sided colonic lesions. We audited the clinical outcomes of our initial experience with colorectal ESD.
METHODS:
We reviewed data collected from a prospective registry of patients who underwent colorectal ESD from December 2014 to March 2018. Therapeutic outcomes and procedure-related complications were analysed.
RESULTS:
A total of 41 patients (mean age 67.4 years, 21 male) underwent colorectal ESD. The distribution of the lesions was as follows: rectum (n = 9), sigmoid colon (n = 8), descending colon (n = 6), splenic flexure (n = 1), transverse colon (n = 5), ascending colon (n = 8) and caecum (n = 4). The mean size was 23 (range 12-50) mm. En bloc resection was achieved in 35 (85.4%) out of 41 patients, and R0 resection or clear resection margins was achieved in 33 (94.3%) of the en bloc resection patients. The lesion was upstaged in 14 (34.1%) patients after ESD. Colonic perforation occurred in 3 (7.3%) patients during ESD and was successfully treated with endoscopic clips. There was no procedure-related bleeding. No patient required surgery for management of complications. The median duration of hospitalisation was 1 (range 0-7) day. Four patients with lesions that were upstaged after ESD, from high-grade dysplasia to intramucosal carcinoma with deep submucosal invasion, were referred for colectomy.
CONCLUSION
Our early outcome data was comparable to that from large published series. ESD is an effective and feasible treatment for colorectal lesions.
6.SingHealth Radiology Archives pictorial essay Part 1: cardiovascular, respiratory and neurological cases.
Mark Bangwei TAN ; Kim Ping TAN ; Joey Chan Yiing BEH ; Eugenie Yi Kar CHAN ; Kenneth Fu Wen CHIN ; Zong Yi CHIN ; Wei Ming CHUA ; Aaron Wei-Loong CHONG ; Gary Tianyu GU ; Wenlu HOU ; Anna Chooi Yan LAI ; Rebekah Zhuyi LEE ; Perry Jia Ren LIEW ; May Yi Shan LIM ; Joshua Li Liang LIM ; Zehao TAN ; Eelin TAN ; Grace Siew Lim TAN ; Timothy Shao Ern TAN ; Eu Jin TAN ; Alexander Sheng Ming TAN ; Yet Yen YAN ; Winston Eng Hoe LIM
Singapore medical journal 2020;61(12):633-640
The Singapore Health Services cluster (SingHealth) radiology film archives are a valuable repository of local radiological cases dating back to the 1950s. Some of the cases in the archives are of historical medical interest, i.e. cerebral angiography in the workup of patients with hemiplegia. Other cases are of historical social interest, being conditions seen during earlier stages of Singapore's development, i.e. bound feet. The archives form a unique portal into the development of local radiology as well as the national development of Singapore. A selection from the archives is published in 2020 in commemoration of the 20th anniversary of the formation of SingHealth, the 55th National Day of Singapore, and the 125th anniversary of the International Day of Radiology. This pictorial essay comprises cardiovascular, respiratory and neurological cases from the archives.
7.SingHealth Radiology Archives pictorial essay Part 2: gastroenterology, musculoskeletal, and obstetrics and gynaecology cases.
Mark Bangwei TAN ; Kim Ping TAN ; Joey Chan Yiing BEH ; Eugenie Yi Kar CHAN ; Kenneth Fu Wen CHIN ; Zong Yi CHIN ; Wei Ming CHUA ; Aaron Wei-Loong CHONG ; Gary Tianyu GU ; Wenlu HOU ; Anna Chooi Yan LAI ; Rebekah Zhuyi LEE ; Perry Jia Ren LIEW ; May Yi Shan LIM ; Joshua Li Liang LIM ; Zehao TAN ; Eelin TAN ; Grace Siew Lim TAN ; Timothy Shao Ern TAN ; Eu Jin TAN ; Alexander Sheng Ming TAN ; Yet Yen YAN ; Winston Eng Hoe LIM
Singapore medical journal 2021;62(1):8-15
The Singapore Health Services cluster (SingHealth) radiology film archives are a valuable repository of local radiological cases dating back to the 1950s. Some of the cases in the archives are of historical medical interest, i.e. cerebral angiography in the workup of patients with hemiplegia. Other cases are of historical social interest, being conditions seen during earlier stages of Singapore's development, i.e. bound feet. The archives form a unique portal into the development of local radiology as well as the national development of Singapore. A selection from the archives is published in commemoration of the International Day of Radiology in 2020, as well as the 200th anniversary of the Singapore General Hospital in 2021. This pictorial essay comprises gastroenterology, musculoskeletal and obstetrics and gynaecology cases from the archives.