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1.
Med J Malaysia ; 78(2): 139-144, 2023 03.
Article En | MEDLINE | ID: mdl-36988521

INTRODUCTION: Intravascular ultrasound (IVUS) is recommended in the use of left main stem (LMS) percutaneous coronary intervention (PCI). Since the LMS diameter is usually larger than other coronary arteries, a new generation everolimus drug-eluting stent (DES), Synergy Megatron DES (Boston Scientific) has better axial and radial strength allowing more post implant overexpansion and consequently better suited for LMS lesions. We performed a study to evaluate the clinical outcomes of PCI using 1) an improved IVUS protocol with optimisation targets and 2) the use of Megatron stents. MATERIALS AND METHODS: This was a study involving LMS PCI coronary lesions using the Synergy Megatron DES. An IVUS protocol using predefined optimisation targets to evaluate for stent malapposition, longitudinal stent deformation, optimal stent expansion >90% of reference lumen and appropriate distal landing zone was used in all cases. The primary end-point was procedural success, defined by successful stent implantation with <30% residual stenosis. The secondary end-point was in-hospital and 30-day major adverse cardiovascular event (MACE). RESULTS: Eight patients with significant LMS stenosis were successfully treated with the Megatron stent. The primary end-point was achieved in all patients. There were no cases of stent malapposition or longitudinal stent deformation, one case did not have optimal LMS stent expansion and one case did not have an appropriate distal landing zone. IVUS optimisation criteria were met in 6 (75%) cases. There were no complications of coronary dissection, slow or no reflow, stent thrombosis or vessel perforation. None of the patients suffered in-hospital or 30-day MACE. The average LMS MLD at baseline was 2.1 ± 0.1mm and the post-PCI LMS MLD was 4.0 ± 0.5mm, with a significant acute luminal gain of 1.9 ± 0.7mm (p<0.01). A post-PCI MSA of 17 ± 3.9 mm2 was numerically superior compared to those documented in other LMS PCI trials. CONCLUSION: This study demonstrates low rates of shortterm major adverse cardiovascular events among patients with LMS PCI using the Megatron stents. It highlights the usefulness of IVUS-guided optimisation in LMS PCI. With the use of intravascular imaging, the new generation stent technology can improve the treatment of large proximal vessels and PCI of LMS lesions.


Coronary Artery Disease , Drug-Eluting Stents , Percutaneous Coronary Intervention , Humans , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/surgery , Everolimus , Percutaneous Coronary Intervention/adverse effects , Coronary Angiography , Constriction, Pathologic/etiology , Treatment Outcome , Ultrasonography, Interventional/methods , Angioplasty
2.
Med J Malaysia ; 78(1): 7-13, 2023 01.
Article En | MEDLINE | ID: mdl-36715184

INTRODUCTION: Coronary artery calcification can lead to suboptimal results when performing coronary angioplasty with conventional techniques. The presence of severe coronary artery calcium increases the complications of percutaneous coronary intervention as it may impede stent delivery and optimal stent expansion. The purpose of this study was to determine the procedural success and safety of orbital atherectomy (OA) in calcified lesions. MATERIALS AND METHODS: This was a prospective single-centre study regarding the utility of OA in the treatment of calcified coronaries. Intravascular ultrasound (IVUS) or optical coherence tomography (OCT) was used in all cases to characterise the severity of calcium pre-procedure, guide vessel sizing and assess procedural success. The primary endpoint was procedural success, defined by successful stent implantation following OA treatment. The secondary endpoint was in-hospital and 30-day major adverse cardiovascular event (MACE). RESULTS: Ten patients with severely calcified lesions were successfully treated with OA. The primary endpoint was achieved in all patients. All of the lesions were severely calcified with concentric calcium. None of the patients suffered in-hospital or 30-day MACE. The average minimal luminal diameter at baseline was 1.7 ± 0.3 mm and the post- PCI luminal diameter was 3.0 ± 0.3 mm, with a significant luminal gain of 1.3 ± 0.3 mm (p < 0.01). Slow flow during procedure occurred in 2 (20%) cases and dissection occurred in 1 (10%) case during procedure. These were successfully treated with stent delivery to achieve TIMI III flow. There were no cases of stent thrombosis or vessel perforation. CONCLUSION: Our experience demonstrates the feasibility and safety of OA in the management of calcified coronary stenosis. Intravascular imaging is an important adjunct to the use of OA to assess the severity of calcified coronary lesions, success of OA treatment and to aid sizing of the vessel for stent implantation. OA is an effective treatment approach to disrupt coronary calcification, facilitating stent implantation with optimal results. It is a safe procedure with good success rate and low rate of complications.


Atherectomy, Coronary , Coronary Artery Disease , Percutaneous Coronary Intervention , Vascular Calcification , Humans , Percutaneous Coronary Intervention/adverse effects , Atherectomy, Coronary/adverse effects , Atherectomy, Coronary/methods , Prospective Studies , Calcium , Vascular Calcification/diagnostic imaging , Vascular Calcification/surgery , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/surgery , Atherectomy , Treatment Outcome , Severity of Illness Index
3.
Med J Malaysia ; 77(4): 500-505, 2022 07.
Article En | MEDLINE | ID: mdl-35902942

INTRODUCTION: Coronary artery calcification can lead to suboptimal results when performing coronary angioplasty with conventional techniques. Shockwave intravascular lithotripsy (IVL) has recently been introduced as a new modality to treat heavily calcified coronary arteries. The purpose of this study was to determine the procedural success and safety of IVL in calcified lesions. MATERIALS AND METHODS: This was a prospective single-centre study regarding the utility of IVL in treatment of calcified coronary arteries. Intravascular ultrasound (IVUS) was used in all cases to characterise the lesions pre procedure and to assess procedural success post procedure. The primary end point was procedural success, defined by IVL treatment and successful stent implantation. The secondary end point was in-hospital and 30-day major adverse cardiovascular event (MACE). RESULTS: Five patients with severely calcified lesions were successfully treated with IVL. The primary end point was achieved in all patients. All of the lesions were severely calcified with concentric calcium. Multiple calcium fractures were identified on IVUS after IVL in all cases. None of the patients suffered in-hospital or 30-day MACE. The average diameter stenosis at baseline was 1.8±0.4mm and the post PCI diameter stenosis was 2.9±0.1mm, with significant acute luminal gain of 1.2±0.3mm (p<0.01). There were no complications of coronary dissection, slow or no reflow, stent thrombosis, or vessel perforation. CONCLUSION: Our initial experience demonstrates the feasibility and safety of IVL in the management of calcified coronary stenosis. The shockwave IVL is an effective treatment approach to disrupt coronary calcification, facilitating stent implantation with optimal results. It is a safe procedure with a good success rate and low rate of complications.


Coronary Artery Disease , Lithotripsy , Percutaneous Coronary Intervention , Vascular Calcification , Calcium , Constriction, Pathologic/etiology , Constriction, Pathologic/therapy , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/therapy , Humans , Lithotripsy/adverse effects , Lithotripsy/methods , Prospective Studies , Registries , Treatment Outcome , Vascular Calcification/diagnostic imaging , Vascular Calcification/etiology , Vascular Calcification/therapy
4.
Disabil Rehabil ; 44(1): 124-130, 2022 Jan.
Article En | MEDLINE | ID: mdl-32374189

PURPOSE: Translating the Neck Disability Index (NDI) into the Malay language (NDI-M); evaluation of psychometric properties in patients with neck pain. METHODS: The NDI-M was translated according to established guidelines. In the first visit, 120 participants completed the NDI-M, visual analogue scale (VAS) for pain and demographic details. 98 participants returned to complete similar questionnaires and the Global Rating of Change (GRoC) scale. The NDI-M was evaluated for internal consistency, test-retest reliability, content validity, construct validity and responsiveness. RESULTS: The NDI-M demonstrated excellent internal consistency (Cronbach's α = 0.84) and good test-retest reliability (ICC2,1 = 0.79). Content validity was confirmed with no floor or ceiling effects. Construct validity was established revealing three-factor subscales explaining 68% of the total variance. The NDI-M showed a moderate correlation with VAS (Rp = 0.49, p < 0.001). Regarding responsiveness, a moderate correlation between NDI-M change scores and VAS change scores was found (Rp = 0.40, p < 0.001). However, there was no significant correlation between NDI-M with GRoC (Rs = 0.11, p = 0.27). CONCLUSIONS: The NDI-M is a reliable and valid tool to measure functional outcomes in patients with neck pain. It is responsive in detecting changes in pain intensity during a patient's rehabilitation journey.Implications for rehabilitationThe NDI was translated into the Malay language and culturally adapted for Malay-speaking patients with neck pain.The NDI-M demonstrated an excellent level of internal consistency and good test-retest reliability. It demonstrated content and construct validity, with three-factor subscales, and moderate responsiveness for pain intensity.The NDI-M is a reliable, valid and responsive instrument to measure functional limitations in patients with neck pain for rehabilitation.


Cross-Cultural Comparison , Language , Disability Evaluation , Humans , Malaysia , Neck Pain/diagnosis , Psychometrics , Reproducibility of Results , Severity of Illness Index , Surveys and Questionnaires , Translations
5.
Med J Malaysia ; 76(2): 125-130, 2021 03.
Article En | MEDLINE | ID: mdl-33742617

INTRODUCTION: The global pandemic of Corona Virus Disease 2019 (COVID-19) has led to the re-purposing of medications, such as hydroxychloroquine and lopinavir-ritonavir in the treatment of the earlier phase of COVID-19 before the recognized benefit of steroids and antiviral. We aim to explore the corrected QT (QTc) interval and 'torsadogenic' potential of hydroxychloroquine and lopinavir-ritonavir utilising a combination of smartphone electrocardiogram and 12-lead electrocardiogram monitoring. MATERIALS AND METHODS: Between 16-April-2020 to 30-April- 2020, patients with suspected or confirmed for COVID-19 indicated for in-patient treatment with hydroxychloroquine with or without lopinavir-ritonavir to the Sarawak General Hospital were monitored with KardiaMobile smartphone electrocardiogram (AliveCor®, Mountain View, CA) or standard 12-lead electrocardiogram. The baseline and serial QTc intervals were monitored till the last dose of medications or until the normalization of the QTc interval. RESULTS: Thirty patients were treated with hydroxychloroquine, and 20 (66.7%) patients received a combination of hydroxychloroquine and lopinavir-ritonavir therapy. The maximum QTc interval was significantly prolonged compared to baseline (434.6±28.2msec vs. 458.6±47.1msec, p=0.001). The maximum QTc interval (456.1±45.7msec vs. 464.6±45.2msec, p=0.635) and the delta QTc (32.6±38.5msec vs. 26.3±35.8msec, p=0.658) were not significantly different between patients on hydroxychloroquine or a combination of hydroxychloroquine and lopinavir-ritonavir. Five (16.7%) patients had QTc of 500msec or more. Four (13.3%) patients required discontinuation of hydroxychloroquine and 3 (10.0%) patients required discontinuation of lopinavirritonavir due to QTc prolongation. However, no torsade de pointes was observed. CONCLUSIONS: QTc monitoring using smartphone electrocardiogram was feasible in COVID-19 patients treated with hydroxychloroquine with or without lopinavir-ritonavir. The usage of hydroxychloroquine and lopinavir-ritonavir resulted in QTc prolongation, but no torsade de pointes or arrhythmogenic death was observed.


COVID-19 Drug Treatment , Electrocardiography , Enzyme Inhibitors/therapeutic use , Hydroxychloroquine/therapeutic use , Long QT Syndrome/diagnosis , Smartphone , Adult , Aged , Antiviral Agents/therapeutic use , Drug Combinations , Female , Humans , Long QT Syndrome/chemically induced , Lopinavir/therapeutic use , Male , Middle Aged , Mobile Applications , Ritonavir/therapeutic use
6.
Sci Rep ; 11(1): 203, 2021 01 08.
Article En | MEDLINE | ID: mdl-33420251

Motor synergies are neural organizations of a set of redundant motor effectors that interact with one another to compensate for each other's error and ensure the stabilization of a performance variable. Recent studies have demonstrated that central nervous system synergistically coordinates its numerous motor effectors through Bayesian multi-sensory integration. Deficiency in sensory synergy weakens the synergistic interaction between the motor effectors. Here, we scrutinize the neuromechanical mechanism underlying this phenomenon through spectral analysis and modeling. We validate our model-generated results using experimental data reported in the literature collected from participants performing a finger force production task with and without tactile feedback (manipulated through injection of anesthetic in fingers). Spectral analysis reveals that the error compensation feature of synergies occurs only at low frequencies. Modeling suggests that the neurophysiological structures involving short-latency back-coupling loops similar to the well-known Renshaw cells explain the deterioration of synergy due to sensory deprivation.


Mechanical Phenomena , Movement/physiology , Sensation/physiology , Adult , Biomechanical Phenomena , Feedback, Sensory , Female , Humans , Male , Models, Neurological
7.
J R Soc Interface ; 17(168): 20200146, 2020 07.
Article En | MEDLINE | ID: mdl-32634368

Foraging bumblebees are electrically charged. Charge accumulation has been proposed to enable their ability to detect and react to electrical cues. One mechanism suggested for bumblebee electro-sensing is the interaction between external electric fields and electric charges accumulating on fine hairs on the cuticular body. Such hairs exhibit several functional adaptations, for example, thermal insulation, pollen capture and notably, the sensing of air motion such as flow currents or low frequency sound particle velocity. Both air motion and electric fields are ubiquitous in the sensory ecology of terrestrial arthropods, raising the question as to whether cuticular hairs respond to both stimuli. Here, a model-theoretical approach is taken to investigate the capacity of bumblebee filiform hairs as electric sensors and compare it to their response to air motion. We find that oscillating air motion and electric fields generate different mechanical responses, depending on stimulus frequency and body geometry. Further, hair morphology can enhance one sensing mode over the other; specifically, higher surface area favours electric sensitivity. Assuming a maximum stable charge on the hair that is limited only by electric breakdown of air, it is expected that an applied oscillating electric field strength of approximately 300 V m-1 produces comparable mechanical response on the hair as a 35 mm s-1 air flow oscillating at 130 Hz-an air disturbance signal similar to that produced by wingbeats of insects within a few bodylengths of the bumblebee. This analysis reveals that bumblebee filiform hairs can operate as bi-modal sensors, responding to both oscillating electric and air motion stimuli in the context of ecologically relevant scenarios.


Electricity , Hair , Animals , Bees , Insecta , Motion , Sound
8.
Med J Malaysia ; 75(2): 164-166, 2020 03.
Article En | MEDLINE | ID: mdl-32281599

We present a rare case of post-antiretroviral therapy (ART) paradoxically worsening of radiological findings in a patient with advanced HIV-infection on treatment for Rhodococcus pneumonia who was misdiagnosed with pulmonary tuberculosis. Despite clinical improvement, serial chest radiographs showed deteriorations a month after starting ART. This was attributed to Immune Reconstitution Inflammatory Syndrome (IRIS) which spontaneously resolved without any treatment.


Actinomycetales Infections/diagnosis , Anti-Retroviral Agents/therapeutic use , HIV Infections/drug therapy , Immune Reconstitution Inflammatory Syndrome/physiopathology , Radiography, Thoracic , Rhodococcus , Adult , Diagnostic Errors , Humans , Immune Reconstitution Inflammatory Syndrome/diagnostic imaging , Male , Outcome Assessment, Health Care
9.
Med J Malaysia ; 74(4): 270-274, 2019 08.
Article En | MEDLINE | ID: mdl-31424032

INTRODUCTION: Sarawak has a population that is geographically and characteristically widely varied. In this study we aimed to determine the demographic characteristics of our patient population who undergo continuous ambulatory peritoneal dialysis (CAPD) and to study the incidence, the microbiology and the outcome of CAPD peritonitis. METHODS: A retrospective record review of all CAPD patients on follow-up at the Miri Hospital, Sarawak, Malaysia from 2014 until 2017 was done. RESULTS AND DISCUSSION: During the 4-year period, the overall peritonitis rate was 0.184 episodes per patient-year. Gram-positive and gram-negative bacteria each constituted one-third of the peritonitis; fungi (2.6%), Mycobacterium tuberculosis (MTB) (5.3%), polymicrobial (2.6%) and sterile culture (26.3%). The most commonly isolated gram-positive bacteria were coagulase-negative Staphylococcus. Our peritonitis rate is comparable to that of other centres i.e., Japan 0.195 and Indonesia 0.25. In comparison, countries like India (0.41), Korea (0.40) and Singapore (0.59) had relatively higher rate of PD-associated peritonitis. Two tuberculosis peritonitis patients died. The rate of catheter removal was approximately 20%. Gram-negative bacteria and MTB have a higher risk of catheter loss. About one-fifth used rainwater to clean their CAPD exit site. Out of this group, 33% did not boil the rainwater prior to usage. CONCLUSION: Patient's characteristics and microbial susceptibility vary in different places of practice. The high rates of culture-negative peritonitis and high mortality risks associated with TB peritonitis warrant special attention. In patients with refractory peritonitis, early catheter removal is warranted in order to reduce mortality and minimize damage to peritoneal membrane.


Gram-Negative Bacterial Infections/etiology , Gram-Positive Bacterial Infections/etiology , Mycoses/etiology , Peritoneal Dialysis, Continuous Ambulatory/adverse effects , Peritonitis/etiology , Adult , Aged , Drug Resistance, Bacterial , Female , Follow-Up Studies , Gram-Negative Bacterial Infections/diagnosis , Gram-Negative Bacterial Infections/epidemiology , Gram-Negative Bacterial Infections/microbiology , Gram-Positive Bacterial Infections/diagnosis , Gram-Positive Bacterial Infections/epidemiology , Gram-Positive Bacterial Infections/microbiology , Humans , Incidence , Malaysia , Male , Microbial Sensitivity Tests , Middle Aged , Mycoses/diagnosis , Mycoses/epidemiology , Mycoses/microbiology , Peritonitis/diagnosis , Peritonitis/epidemiology , Peritonitis/microbiology , Retrospective Studies , Risk Factors
10.
Med J Malaysia ; 74(4): 328-330, 2019 08.
Article En | MEDLINE | ID: mdl-31424042

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is primarily a familial disease with autosomal dominant inheritance. Incomplete penetrance and variable expression are common, resulting in broad disease spectrum. Three patterns of phenotypic expression have been described: (1) "classic" subtype, with predominant right ventricle involvement, (2) "left dominant" subtype, with early and dominant left ventricle involvement, and (3) "biventricular" subtype, with both ventricles equally affected. Genotypephenotype associations have been described, but there are other genetic and non-genetic factors that can affect disease expression. We describe two different phenotypic expressions of ARVC in a family.


Arrhythmogenic Right Ventricular Dysplasia/diagnosis , Biological Variation, Population , Phenotype , Siblings , Adult , Echocardiography , Electrocardiography , Fatal Outcome , Female , Humans , Male
11.
Org Biomol Chem ; 17(31): 7380-7387, 2019 08 07.
Article En | MEDLINE | ID: mdl-31342036

To develop a facile method for detecting denatured collagen, we investigated the structure-activity relationship of cyclic collagen-mimetic peptides (cCMPs). Reported cCMP prototypes tend to self-assemble and they must be disassembled just before use. Introducing charge repulsion and a deformation in the peptide backbone structure enabled cCMPs to detect denatured collagen without a pre-treatment for disassembly. Using the optimized cCMP, types I-V collagen were detected by western blotting and denatured collagen fibrils were visualized in a cell culture system.


Collagen/analysis , Peptides, Cyclic/chemistry , Animals , Cells, Cultured , Fibroblasts/chemistry , Mice , Structure-Activity Relationship
12.
Osteoarthritis Cartilage ; 27(7): 1057-1063, 2019 07.
Article En | MEDLINE | ID: mdl-30922981

OBJECTIVES: To develop a staging system that could better reflect symptoms by the spurs quantification in the fossa and joint space narrowing using computed tomography (CT) for elbow arthritis and to evaluate its reproducibility with multiple readers. METHODS: This retrospective study evaluated 81 cases of primary elbow osteoarthritis using both plain radiography and CT. Qualitative and quantitative analyses were independently performed by four orthopedic surgeons using previous and newly proposed staging systems. The reproducibility of the new system was analyzed with intraclass correlation coefficients (ICC). Correlations between symptoms and radiologic classification were assessed using Pearson's correlation coefficient (PCC). RESULTS: The interobserver agreement (1) and intraobserver agreement (2) among the four evaluators was present by ICC. (1) The system of Hastings and Rettig [first observation, 0.544 (95% confidence interval (CI), 0.436-0.649); second observation, 0.582 (95% CI, 0.478-0.682)] and Broberg and Morrey's staging system [first observation, 0.620 (95% CI, 0.521-0.714); second observation, 0.656 (95% CI, 0.562-0.743)] showed substantial and moderate retrospective agreement, whereas the CT-based staging system showed almost perfect agreement [first observation, 0.867 (95% CI, 0.820-0.906); second observation, 0.909 (95% CI, 0.875-0.936)]. (2) The intraobserver agreement was almost perfect in the Brogerg and Morrey's and CT-based staging systems. CT-based staging showed high correlation with visual analogue scale (PCC 0.754, P < 0.001) and Mayo elbow performance score (PCC -0.614, P < 0.001) and moderate correlation with range of motion (PCC -0.458, P < 0.001). CONCLUSIONS: CT-based staging system was highly reproducible and clinically feasible than previous plain radiograph-based staging systems.


Elbow Joint/diagnostic imaging , Osteoarthritis/diagnostic imaging , Pain Measurement , Range of Motion, Articular/physiology , Tomography, X-Ray Computed/methods , Adult , Aged , Cohort Studies , Elbow Joint/pathology , Female , Humans , Male , Middle Aged , Observer Variation , Osteoarthritis/classification , Osteoarthritis/pathology , Physical Examination/methods , Radiography/methods , Retrospective Studies , Severity of Illness Index
13.
Malays Fam Physician ; 13(2): 10-18, 2018.
Article En | MEDLINE | ID: mdl-30302178

INTRODUCTION: Achieving optimal glycated hemoglobin (HbA1c), blood pressure (BP), and LDL-Cholesterol (LDL-C) in patients mitigates macro- and micro-vascular complications, which is the key treatment goal in managing type 2 diabetes mellitus (T2DM). This study aimed to determine the proportion of patients in an urban community with T2DM and the above modifiable conditions attaining triple vascular treatment goals based on current practice guidelines. METHODS: A questionnaire was distributed to adult Asian patients with dyslipidemia at two primary care clinics (polyclinics) in northeastern Singapore. The demographic and clinical data for this sub-population with both T2DM and dyslipidemia were collated with laboratory and treatment information retrieved from their electronic health records. The combined data was then analyzed to determine the proportion of patients who attained triple treatment goals, and logistic regression analysis was used to identify factors associated with this outcome. RESULTS: 665 eligible patients [60.5% female, 30.5% Chinese, 35% Malays, and 34.4% Indians] with a mean age of 60.6 years were recruited. Of these patients, 71% achieved LDL-C ≤2.6 mmol/L, 70.4% had BP

14.
Malays Fam Physician ; 13(2): 29-31, 2018.
Article En | MEDLINE | ID: mdl-30302181

Cardiovascular symptoms presenting in a patient with dengue fever may post a diagnostic dilemma. We describe a case of dengue myocarditis mimicking an acute myocardial infarction in a 56-year-old woman.

15.
Chembiochem ; 19(15): 1613-1617, 2018 08 06.
Article En | MEDLINE | ID: mdl-29756312

We report here a new class of collagen-binding peptides, cyclic collagen-mimetic peptides (cCMPs), that efficiently hybridize with the triple-helix-forming portions of collagen. cCMPs are composed of two parallel collagen-like (Xaa-Yaa-Gly)n strands with both termini tethered by covalent linkages. Enzyme-linked immunosorbent assays and western blotting analysis showed that cCMPs exhibit more potent affinity toward collagen than reported collagen-binding peptides and can specifically detect different collagen polypeptides in a mixture of proteins. Collagen secreted from cultured cells was detected by confocal microscopy with fluorescein-labeled cCMP. The cCMP is also shown to detect sensitively folding intermediates in the endoplasmic reticulum, something that was difficult to visualize with conventional collagen detectors. Molecular-dynamics simulations suggested that a cCMP forms a more stably hybridized product than its single-chain counterpart; this could explain why cCMP has higher affinity toward denatured collagen. These results indicate the usefulness of cCMPs as tools for detecting denatured collagen.


Collagen/analysis , Fluorescein/chemistry , Fluorescent Dyes/chemistry , Peptides, Cyclic/chemistry , Amino Acid Sequence , Animals , Blotting, Western , Cell Line , Enzyme-Linked Immunosorbent Assay , Mice , Microscopy, Confocal
16.
Pharmacogenomics J ; 18(2): 275-280, 2018 04.
Article En | MEDLINE | ID: mdl-28418010

6-Mercaptopurine (6-MP) is a main component of childhood acute lymphoblastic leukemia (ALL) treatment. Some candidate gene variants are associated with its toxicities, but the major variants and effects of combined variants remain unclear. We used Cox regression analysis to evaluate the time-dependent association between candidate variants and the cumulative incidence of 6-MP intolerability in 95 Japanese patients. The major risk factors for severe leukopenia were ABCC4 rs3765534, NUDT15 rs116855232 and rs186364861 in multi-covariate analysis (P<0.05). NUDT15 intermediate activity variant, that is, heterozygous rs116855232 or rs186364861 variant, and the ABCC4 rs3765534 variant showed leukopenia more frequently than either variant alone. All patients with both the intermediate activity NUDT15 variant and the ABCC4 rs3765534 variant suffered from leukopenia, and 57.1% patients required 50% protocol dose by day 168. These data indicate that NUDT15 and ABCC4 are major factors for 6-MP intolerability and that the interaction between these variants enhances intolerability to 6-MP.


Antimetabolites, Antineoplastic/adverse effects , Asian People/genetics , Mercaptopurine/adverse effects , Multidrug Resistance-Associated Proteins/genetics , Polymorphism, Single Nucleotide/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Pyrophosphatases/genetics , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Japan/epidemiology , Leukopenia/blood , Leukopenia/chemically induced , Leukopenia/genetics , Male , Pharmacogenomic Variants/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/epidemiology
17.
Med J Malaysia ; 73(6): 376-381, 2018 12.
Article En | MEDLINE | ID: mdl-30647207

INTRODUCTION: The efficacy of blood pressure (BP) reduction with salt restriction in CKD subjects and its sustainability is not well established. METHODS: We enrolled 75 hypertensive patients with CKD into one-month salt restricting diet. 24-hour urinary sodium and potassium was measured to verify their salt intake followed by 1½ year follow-up. RESULTS: Their creatinine clearance was 43 ± standard deviation 33ml/min/1.73m2. Urinary Na excretion (24HUNa) was 173±129mmol/day, reducing to 148±81 by 31±6 day. Mean, systolic and diastolic BP (MBP, SBP, DBP) were reduced from 102±9 to 97±11 (p<0.001), 148±10 to 139±16 (p<0.001), 78±12 to 75±12 mmHg (p=0.012) respectively. Moderate correlations were shown between reductions in 24-hour urinary Na and MBP, SBP, DBP: r=0.366, 0.260, 0.365; p=0.001, 0.025, 0.001; whereas 24-hour urinary Na-K ratio showed mild correlation. Subjects have some tendency to drift back to previous Na intake profile in follow-up and thus repetitive education is necessary. In subanalysis, 34 subjects with baseline 24HUNa >150 mmol/day, benefited significantly with MBP, SBP, DBP reduction from 102±9 to 95±9 (p=0.001), 146±10 to 135±14 mmHg (p=0.001), 80±11 to 75±11 mmHg (p=0.002) in line with 24HUNa reduction from 253±154 to 163±87mmol/day (p=0.004) and urinary protein-creation ratio reduction from geometric mean of 95 to 65 g/mol. Thirty five subjects with 24HUNa reduction of >20mmol/day have significant reduction in MBP, SBP, DBP: -8 vs -2, -15 vs -4, -5 vs -2 mmHg (p=0.027, 0.006, 0.218) and urinary protein-creatinine ratio: -82 vs 2g/mol (p=0.030) compared to the other forty subjects. CONCLUSION: Quantification of 24-hour urinary Na helps in predicting potential antihypertensive effect with dietary salt reduction of CKD subjects. Salt restriction reduces BP especially in patients with estimated daily sodium intake of >150mmol/day. Reduction in sodium intake beyond 20mmol/day reduced both BP and proteinuria.


Hypertension/diet therapy , Renal Insufficiency, Chronic/complications , Sodium, Dietary/administration & dosage , Female , Humans , Hypertension/etiology , Male , Middle Aged , Potassium/urine , Sodium/urine
18.
Med J Malaysia ; 72(4): 209-214, 2017 08.
Article En | MEDLINE | ID: mdl-28889131

INTRODUCTION: In Malaysia, the prevalence of missed opportunities for HIV-testing is unknown. Missed opportunities have been linked to late diagnosis of HIV and poorer outcome for patients. We describe missed opportunities for earlier HIV-testing in newly-HIV-diagnosed patients. METHODS: Cross sectional study. Adult patients diagnosed with HIV infection and had at least one medical encounter in a primary healthcare setting during three years prior to diagnosis were included. We collected data on sociodemographic characteristics, patient characteristics at diagnosis, HIV-related conditions and whether they were subjected to risk assessment and offered HIV testing during the three years prior to HIV diagnosis. RESULTS: 65 newly HIV-diagnosed patients (male: 92.3%; Malays: 52.4%; single: 66.7%; heterosexual: 41%; homosexual 24.6%; CD4 <350 at diagnosis: 63%). 93.8% were unaware of their HIV status at diagnosis. Up to 56.9% had presented with HIV-related conditions at a primary healthcare facility during the three years prior to diagnosis. Slightly more than half were had risk assessment done and only 33.8% were offered HIV-testing. CONCLUSIONS: Missed opportunities for HIV-testing was unacceptably high with insufficient risk assessment and offering of HIV-testing. Risk assessment must be promoted and primary care physicians must be trained to recognize HIV-related conditions that will prompt them to offer HIVtesting.


AIDS Serodiagnosis , HIV Infections/diagnosis , Tertiary Care Centers/statistics & numerical data , AIDS Serodiagnosis/methods , AIDS Serodiagnosis/statistics & numerical data , Adult , Cross-Sectional Studies , Early Diagnosis , Female , Humans , Malaysia , Male , Middle Aged , Referral and Consultation/statistics & numerical data , Young Adult
19.
J Forensic Leg Med ; 48: 15-21, 2017 May.
Article En | MEDLINE | ID: mdl-28407514

Forensic odontology plays a vital role in the identification and age estimation of unknown deceased individuals. The purpose of this study is to estimate the chronological age from Cone-Beam Computed Tomography (CBCT) images by measuring the buccal alveolar bone level (ABL) to the cemento-enamel junction and to investigate the possibility of employing the age-related structural changes of teeth as studied by Gustafson. In addition, this study will determine the forensic reliability of employing CBCT images as a technique for dental age estimation. A total of 284 CBCT images of Malays and Chinese patients (150 females and 134 males), aged from 20 years and above were selected, measured and stages of age-related changes were recorded using the i-CAT Vision software. Lower first premolars of both left and right side of the jaw were chosen and the characteristics described by Gustafson, namely attrition, secondary dentine formation and periodontal recession were evaluated. Linear regression analysis was performed for the buccal bone level and the R values obtained were 0.85 and 0.82 for left and right side respectively. Gustafson's characteristics were analysed using multiple regression analysis with chronological age as the dependent variable. The results of the analysis showed R values ranged from 0.44 to 0.62. Therefore it can be safely concluded that the buccal bone level highly correlated with the chronological age and is consequently the most suitable age-related characteristic for forensic age estimation.


Age Determination by Teeth/methods , Alveolar Process/diagnostic imaging , Dental Cementum/diagnostic imaging , Dental Enamel/diagnostic imaging , Adult , Alveolar Process/growth & development , Bicuspid/diagnostic imaging , Cementogenesis , Cone-Beam Computed Tomography , Cross-Sectional Studies , Dental Enamel/growth & development , Dentin, Secondary/diagnostic imaging , Female , Gingival Recession/diagnostic imaging , Humans , Linear Models , Malaysia , Male , Middle Aged , Retrospective Studies , Young Adult
20.
Malays Fam Physician ; 12(3): 28-29, 2017.
Article En | MEDLINE | ID: mdl-29527277
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