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Mild beta-thalassemia intermedia caused by compound heterozygosity for (G)gamma((A)gammadeltabeta)(o)/beta-thalassemia and molecular characterization of the defect in four Chinese families

Tan JAMA, Yap SF, Tan KL, Wong YC, Wee YC, Kok JL

Acta Haematol., 2003;109(4):169-75.
PMID: 12853688 DOI: 10.1159/000070965

Molecular characterization of the compound heterozygous condition - (G)gamma((A)gammadeltabeta)(o)/beta-thalassemia - in four families showing mild beta-thalassemia intermedia was carried out using DNA amplification techniques. Using the Amplification Refractory Mutation System (ARMS) to confirm the beta-mutations and DNA amplification to detect the 100-kb Chinese-specific (G)gamma((A)gammadeltabeta)(o)-deletion, ()two families were confirmed to possess (G)gamma((A)gammadeltabeta)(o)/beta-thalassemia with the IVSII No. 654 beta(+)-allele. In the third family, the (G)gamma((A)gammadeltabeta)(o)-deletion was confirmed in the father and the mother was a beta-thalassemia carrier with the cd 41-42 beta(o)-allele. Their affected child with (G)gamma((A)gammadeltabeta)(o)/beta-thalassemia was found to be transfusion dependent. The same (G)gamma((A)gammadeltabeta)(o)-deletion and beta-thalassemia (cd 41-42) was also confirmed in a fourth family. In addition, the mother was also diagnosed with Hb H disease (genotype -alpha(3.7)/-(SEA)). Both the children were found to possess (G)gamma((A)gammadeltabeta)(o)/beta-thalassemia but they were not transfusion dependent and this could be due to co-inheritance of alpha-thalassemia-2 (genotype-alpha(3.7)/alphaalpha) in the children together with their compound heterozygous condition.
Transcutaneous bilirubinometry in fullterm Chinese and Malay infants

Tan KL

Acta Paediatr Scand, 1982 Jul;71(4):593-6.
PMID: 7136674
An epidemiological study of developmental dysplasia of the hip in infants in Singapore

Ang KC, Lee EH, Lee PY, Tan KL

Ann Acad Med Singap, 1997 Jul;26(4):456-8.
PMID: 9395810

The incidence of congenital dislocation of the hip (CDH) in Singapore and Malaysia has been reported as being lower than in the West. In our hospital, we have seen an increasing number of congenital hip dislocation as well as dysplastic hips. We undertook a prospective study from December 1989 to December 1994 of 20,000 live births. The neonates were all screened by a consultant neonatologist and the findings were confirmed by a consultant paediatric orthopaedic surgeon. All babies had plain X-rays at 3 months and an acetabular index (AI) of 30 degrees or more was considered dysplastic. All babies with positive signs were followed up for 1 year and again had radiographs taken at 1 year. Comparison of plain X-rays and ultrasound assessment in a subgroup of 130 neonates showed that 64% of patients with AI > 20 degrees had hip dysplasia by ultrasonographic (alpha angle < 60 degrees) The incidence of dysplastic hips was 16.8 per 1000 live births. The overall incidence of neonates with dislocated hips was 4.7 per 1000 live births. The Malays were most affected with an incidence of 5.4 per 1000 live births. The incidence of developmental dysplasia of the hip in Singapore is higher than previously reported, with the Malays having the highest incidence. A significant number of babies with clicking hips have radiological evidence of acetabular dysplasia (AI > 30 degrees). One-third of the babies' hips were still dysplastic at 1 year of age. A well-organised screening programme with experienced examiners has proved to be useful in making early and accurate clinical diagnosis.
Extremes of foetal birthweight for gestation in infants of diabetic mothers

Kek LP, Ng CS, Chng KP, Ratnam SS, Cheah JS, Yeo PB, et al.

Ann Acad Med Singap, 1985 Apr;14(2):303-6.
PMID: 4037690

100 patients were registered at the Diabetic Clinic in 1981, where they were managed by a team of physician, obstetrician and paediatrician, based on a preset protocol. Only 92 patients were eventually analysed. The study showed a 1.3% incidence of pregnancies complicated by diabetes mellitus. The mean birthweights of infants of both gestational and established diabetics were heavier than that of the general population by race and gestation. 25% of the 92 infants of diabetic mothers have birthweight exceeding the 90th centile of population. Further division of the 92 patients into the "true gestational" diabetics, as shown by an oral glucose tolerance test performed 6 weeks post-natally, also showed a 25% incidence of macrosomia. Late antenatal booking, delayed detection of abnormal glucose tolerance and treatment attributed to the high incidence of macrosomia. Only one infant had birthweight below the tenth centile. There were no perinatal mortality in the 92 patients studied. Macrosomia is a common complication in infants of diabetic mothers despite a physician-obstetrician joint-care system. Also, the risk of having macrosomia amongst gestational diabetics is high.
Combined team management of diabetes mellitus in pregnancy

Ng CS, Lim LS, Chng KP, Lim P, Cheah JS, Yeo PP, et al.

Ann Acad Med Singap, 1985 Apr;14(2):297-302.
PMID: 4037689

225 women with diabetes in pregnancy were managed by a team of obstetricians, physicians (endocrinologists) and paediatricians from the National University of Singapore. A protocol of management was formulated and followed. The incidence of 1.1% or 1 in 90 pregnancies was found, with significantly higher incidence in Indians and lower in Malays. There were 37 established diabetics and 188 diagnosed during pregnancy. Of these (188), 74 were gestational diabetics. All the women were treated with Insulin and Diet or Diet alone. 177 (79%) were treated with Insulin and Diet. Blood sugar profiles were done for monitoring diabetic control. 72.8% of the women were between para 0 and 1 and 85.2% between the ages of 20 and 34. 72.5% of the women delivered at 38 weeks gestation or later. 48.9% went into spontaneous labour, 32.4% were induced and 18.7% had elective caesarean section. 62.2% of the women had labour of less than 12 hours. The overall caesarean section rate was 41.7%. There were 3 stillbirths and 2 neonatal deaths. The perinatal mortality rate was 2.2%. Thirteen babies had congenital malformations (5.8%). 77.8% of the babies had Apgar score of 7 or more at 5 minutes after delivery. 79.1% of the babies weighed between 2.5 kgm and 3.9 kgm. Pre-eclamptic toxaemia was the commonest complication in pregnancy followed by Urinary Tract Infection and Polyhydramnios. Postpartum complications in the mother were confined to 14 women (6.2%), and wound infection or breakdown was the commonest cause.
Perinatal mortality with particular reference to the Singapore situation

Tan KL

Ann Acad Med Singap, 1984 Apr;13(2):252-63.
PMID: 6497323

Perinatal mortality rates have been gradually declining in all countries. The initial decline mainly resulted from improvements in the late foetal mortality rates. Later with improvements in neonatal care, early neonatal mortality rates also improved. The developed countries have consistently shown better results than the developing countries, an indication of the higher standard of living, general health as well as the delivery of health care in these countries. In the Singapore situation, a rapid improvement in perinatal mortality was initially observed due to improvements in the late foetal mortality, followed later by reduction in the early neonatal mortality due to upgrading of neonatal intensive care. The perinatal mortality rate is lowest in the Chinese compared to the Indians and Malays, most likely due to the dietary practices of the three ethnic groups in Singapore; while the Chinese encourage extra nutrition in the pregnant female, the Malays and Indians tend to practise dietary restriction during this period. The improved nutrition of the pregnant mother is a factor in improving the perinatal mortality.
Fulltext Transposed Basilic Vein Fistula: A Credible Option

Leong BD, Zainal AA, Hanif H, Tajri HM, Govindarajantran N, Pillay K, et al.

Ann Vasc Dis, 2018 Jun 25;11(2):223-227.
PMID: 30116415 DOI: 10.3400/avd.oa.18-00018

Objective: Native fistula creation for hemodialysis in patients who have exhausted all their superficial veins presents a challenge to vascular practice. We review our experience in transposed basilic vein fistula (BVT) creation and its usage for hemodialysis. Materials and Methods: We analyzed the hospital operative registry from January 2009 till June 2012 to identify the total number of BVT created in our center. Medical records of all patients were traced, and patients were interviewed using a standard proforma. In our center, BVT is performed as a two-stage procedure. All patients were routinely assessed with duplex scan preoperatively and postoperatively. Results: Two hundred thirty-nine patients were recruited in the study. Of these patients, 50.6% were male and 49.4% were female. Mean age was 53.4 years. Of these patients, 81.2% had history of other previous fistula creation. Risk factors profile includes diabetes mellitus in 59.8%, hypertension in 86.2%, and smoking in 13.0%. Of these patients, 84.5% had no operative complication. Commonest complication was wound infection, 6.3%, followed by hemorrhage or hemotoma required surgical intervention, 5.9%, and pseudoaneurysm, 1.3%. Primary and secondary patencies were at 84.2% and 86.1% at 1 year and 67.7% and 70.5% at 3 years, respectively. Conclusion: BVT is a credible option for challenging patients with absence of superficial veins for native fistula creation with good patency and low operative complication rate. Preoperative ultrasound assessment improves patient selection and outcome of BVT.
Induction of Apoptosis and Autophagy by Ternary Copper Complex Towards Breast Cancer Cells

Lee ZY, Leong CH, Lim KUL, Wong CCS, Pongtheerawan P, Arikrishnan SA, et al.

Anticancer Agents Med Chem, 2021 Jul 26.
PMID: 34315396 DOI: 10.2174/1871520621666210726132543

BACKGROUND: Copper complex has been gaining much attention in anticancer research as targeted agent since cancer cells uptake more copper than non-cancerous cells. Our group has synthesised a ternary copper complex which is composed of 1,10-phenanthroline and tyrosine [Cu(phen)(L-tyr)Cl].3H20. These two payloads are designed to cleave DNA and inhibit protein degradation system (proteasome) concurrently in cancer cells, making this copper complex a dual-target compound.
OBJECTIVE: Current study was carried out to investigate the mode of cell death and role of autophagy induced by [Cu(phen)(L-tyr)Cl].3H20 in MCF-7 and MDA-MB-231 breast cancer cells.
METHODS: Growth inhibition of [Cu(phen)(L-tyr)Cl].3H20 towards MDA-MB-231 and human non-cancerous MCF10A breast cells was determined by MTT assay. Annexin-V-FITC/PI and cell cycle analysis were evaluated by flow cytometry. The expression of p53, Bax, caspase-9, caspase-7, caspase-3 and LC3 were determined using western blot analysis. The cells were then co-treated with hydroxychloroquine to ascertain the role of autophagy induced by [Cu(phen)(L-tyr)Cl].3H20.
RESULTS: [Cu(phen)(L-tyr)Cl].3H20 inhibited the growth of cancer cells dose-dependently with less toxicity towards MCF10A cells. Additionally, [Cu(phen)(L-tyr)Cl].3H20 induced apoptosis and cell cycle arrest towards MCF-7 and MDA-MB-231 breast cancer cells possibly via regulation of p53, Bax, caspase-9, caspase-3 and capase-7. The expression of LC3II was upregulated in both cancer cell lines upon treatment with [Cu(phen)(L-tyr) Cl].3H20, indicating the induction of autophagy. Co-treatment with autophagy inhibitor hydroxychloroquine significantly enhanced growth inhibition of both cell lines, suggesting that the autophagy induced by [Cu(phen)(L-tyr) Cl].3H20 in both breast cancer cells was promoting cell survival.
CONCLUSION: [Cu(phen)(L-tyr)Cl].3H20 holds great potential to be developed for breast cancer treatment.
Chemopreventive potential of Annona muricata L leaves on chemically-induced skin papillomagenesis in mice

Hamizah S, Roslida AH, Fezah O, Tan KL, Tor YS, Tan CI

Asian Pac J Cancer Prev, 2012;13(6):2533-9.
PMID: 22938417

Annona muricata L (Annonaceae), commonly known as soursop has a long, rich history in herbal medicine with a lengthy recorded indigenous use. It had also been found to be a promising new anti-tumor agent in numerous in vitro studies. The present investigation concerns chemopreventive effects in a two-stage model of skin papillomagenesis. Chemopreventive effects of an ethanolic extract of A. muricata leaves (AMLE) was evaluated in 6-7 week old ICR mice given a single topical application of 7,12-dimethylbenza(α)anthracene (DMBA 100 μg/100 μl acetone) and promotion by repeated application of croton oil (1% in acetone/ twice a week) for 10 weeks. Morphological tumor incidence, burden and volume were measured, with histological evaluation of skin tissue. Topical application of AMLE at 30, 100 and 300 mg/kg significantly reduced DMBA/croton oil induced mice skin papillomagenesis in (i) peri-initiation protocol (AMLE from 7 days prior to 7 days after DMBA), (ii) promotion protocol (AMLE 30 minutes after croton oil), or (iii) both peri-initiation and promotion protocol (AMLE 7 days prior to 7 day after DMBA and AMLE 30 minutes after croton oil throughout the experimental period), in a dose dependent manner (p<0.05) as compared to carcinogen-treated control. Furthermore, the average latent period was significantly increased in the AMLE-treated group. Interestingly, At 100 and 300 mg/ kg, AMLE completely inhibited the tumor development in all stages. Histopathological study revealed that tumor growth from the AMLE-treated groups showed only slight hyperplasia and absence of keratin pearls and rete ridges. The results, thus suggest that the A.muricata leaves extract was able to suppress tumor initiation as well as tumor promotion even at lower dosage.
Phototherapy for neonatal jaundice in Chinese, Malay and Indian infants

Tan KL

Aust Paediatr J, 1976 Mar;12(1):43-6.
PMID: 962730
Fulltext Functional transcriptome analysis of the postnatal brain of the Ts1Cje mouse model for Down syndrome reveals global disruption of interferon-related molecular networks

Ling KH, Hewitt CA, Tan KL, Cheah PS, Vidyadaran S, Lai MI, et al.

BMC Genomics, 2014;15:624.
PMID: 25052193 DOI: 10.1186/1471-2164-15-624

The Ts1Cje mouse model of Down syndrome (DS) has partial triplication of mouse chromosome 16 (MMU16), which is partially homologous to human chromosome 21. These mice develop various neuropathological features identified in DS individuals. We analysed the effect of partial triplication of the MMU16 segment on global gene expression in the cerebral cortex, cerebellum and hippocampus of Ts1Cje mice at 4 time-points: postnatal day (P)1, P15, P30 and P84.
Fulltext Harvesting the maximum length of sciatic nerve from adult mice: a step-by-step approach

Bala U, Tan KL, Ling KH, Cheah PS

BMC Res Notes, 2014;7:714.
PMID: 25304607 DOI: 10.1186/1756-0500-7-714

Over the past several decades, many studies concerning peripheral nerve damage or regeneration have been performed. Mice have been widely used for many of these studies, with the sciatic nerve being the most targeted and preferred nerve. Therefore, techniques for harvesting mouse sciatic nerves of a maximum length that is sufficient for different analyses will be highly valuable. Here we describe a simple step-by-step guide for harvesting the maximum length of mouse sciatic nerve and compare the length of the harvested nerves gathered with the proposed method with nerves obtained using a conventional mid-thigh incision approach.
Fulltext Observational study investigating the prevalence of asymptomatic stage B heart failure in patients with type 2 diabetes who are not known to have coronary artery disease

Oo MM, Tan Chung Zhen I, Ng KS, Tan KL, Tan ATB, Vethakkan SR, et al.

BMJ Open, 2021 01 21;11(1):e039869.
PMID: 33478961 DOI: 10.1136/bmjopen-2020-039869

OBJECTIVE: To identify the prevalence of stage B heart failure (SBHF) in patients with type 2 diabetes mellitus (T2DM) with no history of cardiovascular disease (CVD).
DESIGN: Observational study.
SETTING: A single-centre study in which eligible patients were recruited from T2DM clinic. Following consent, patients completed a questionnaire and underwent physical examinations. Patients had blood drawn for laboratory investigations and had a transthoracic echocardiography.
PARTICIPANTS: A total of 305 patients who were not known to have CVD were recruited. Patients with deranged liver function tests and end stage renal failure were excluded.
MAIN OUTCOME MEASURES: Echocardiographic parameters such as left ventricular ejection fraction, left ventricular mass index (LVMI), left ventricular hypertrophy, left atrial enlargement and diastolic function were examined.
RESULTS: A total of 305 patients predominantly females (65%), with mean body mass index of 27.5 kg/m2 participated in this study. None of them had either a history or signs and symptoms of CVD. Seventy-seven percent of patients had a history of hypertension and 83% of this study population had T2DM for more than 10 years. Mean HbA1c of 8.3% was recorded. Almost all patients were taking metformin. Approximately, 40% of patients were on newer anti-T2DM agents such as sodium-glucose cotransporter-2 and dipeptidyl peptidase 4 inhibitors. Fifty-seven percent (n=174) of the study population had SBHF at the time of study: diastolic dysfunction, increased LVMI and increased left atrial volume index (LAVI) were noted in 51 patients (17%), 128 patients (42%) and 98 patients (32%), respectively. Thirty-seven patients (12%) had both increase LVMI and LAVI.
CONCLUSION: Our study has revealed a high prevalence of SBHF in T2DM patients without overt cardiac disease in Malaysia that has one of the highest prevalence of TDM in the world.
Fulltext Leucine-Rich Alpha-2-Glycoprotein: A Novel Predictor of Diastolic Dysfunction

Loch A, Tan KL, Danaee M, Idris I, Ng ML

Biomedicines, 2023 Mar 20;11(3).
PMID: 36979923 DOI: 10.3390/biomedicines11030944

Leucine-rich α2-glycoprotein (LRG1) mediates cardiac fibrocyte activation. It is upregulated in inflammatory conditions, atherosclerosis, and fibrosis. Diastolic dysfunction (DD) is due to myocardial fibrosis. This cross-sectional study examined the relationship between LRG1 and DD. Patients with symptoms of chronic coronary ischemia were recruited. Patients with symptoms of overt heart failure, ejection fraction (EF) < 55%, impaired renal function, infection, and recent trauma were excluded from the study. Clinical parameters examined were SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery (SYNTAX) score, echocardiographic assessment, and LRG1 levels. Binary stepwise logistic regression was used to evaluate the association between LRG1 and DD. Receiver Operating Characteristic (ROC) analysis was used to determine optimal cut-off values and predictive performance of LRG1. A total of 94 patients were enrolled in the study, with 47 having a clinical diagnosis of DD. Plasma LRG1 was significantly (U = 417.00, p < 0.001) higher in the DD group (M = 14) compared to the No-DD group (M = 8) by Mann-Whitney U test. There were higher SYNTAX scores in the DD group (M = 24.5) compared with No-DD (M = 7). LRG1 had significant predictability of DD (OR = 1.32 (95% CI: 1.14-1.53)). The ROC showed an AUC = 0.89 (95% CI: 0.82-0.95). LRG1 had a 78% sensitivity (95% CI: 65.3-87.7) and 72.3% specificity (95% CI: 57.4-84.4) for predicting DD at a cut-off value of "9". In conclusion, we identified LRG1 as a novel independent predictor of DD. Further studies are warranted to validate the utility of LRG1 in predicting DD.
Fulltext NUB1 and FAT10 Proteins as Potential Novel Biomarkers in Cancer: A Translational Perspective

Arshad M, Abdul Hamid N, Chan MC, Ismail F, Tan GC, Pezzella F, et al.

Cells, 2021 08 24;10(9).
PMID: 34571823 DOI: 10.3390/cells10092176

Cancer increases the global disease burden substantially, but it remains a challenge to manage it. The search for novel biomarkers is essential for risk assessment, diagnosis, prognosis, prediction of treatment response, and cancer monitoring. This paper examined NEDD8 ultimate buster-1 (NUB1) and F-adjacent transcript 10 (FAT10) proteins as novel biomarkers in cancer. This literature review is based on the search of the electronic database, PubMed. NUB1 is an interferon-inducible protein that mediates apoptotic and anti-proliferative actions in cancer, while FAT10 is a ubiquitin-like modifier that promotes cancer. The upregulated expression of both NUB1 and FAT10 has been observed in various cancers. NUB1 protein binds to FAT10 non-covalently to promote FAT10 degradation. An overexpressed FAT10 stimulates nuclear factor-kappa β, activates the inflammatory pathways, and induces the proliferation of cancer. The FAT10 protein interacts with the mitotic arrest deficient 2 protein, causing chromosomal instability and breast tumourigenesis. FAT10 binds to the proliferating cell nuclear antigen protein and inhibits the DNA damage repair response. In addition, FAT10 involves epithelial-mesenchymal transition, invasion, apoptosis, and multiplication in hepatocellular carcinoma. Our knowledge about them is still limited. There is a need to further develop NUB1 and FAT10 as novel biomarkers.
Molecular defects in the beta-globin gene identified in different ethnic groups/populations during prenatal diagnosis for beta-thalassemia: a Malaysian experience

Tan JA, George E, Tan KL, Chow T, Tan PC, Hassan J, et al.

Clin Exp Med, 2004 Dec;4(3):142-7.
PMID: 15599663 DOI: 10.1007/s10238-004-0048-x

Beta-thalassemia is the most-common genetic disorder of hemoglobin synthesis in Malaysia, and about 4.5% of the population are heterozygous carriers of the disorder. Prenatal diagnosis was performed for 96 couples using the Amplification Refractory Mutation System and Gap-Polymerase Chain Reaction. We identified 17 beta-globin defects-initiation codon for translation (T-G), -29 (A-G), -28 (A-G), CAP +1 (A-C), CD 8/9 (+G), CD 15 (G-A), CD 17 (A-T), CD 19 (A-G), Hb E (G-A), IVS1-1 (G-T), IVS1-5 (G-C), CD 41/42 (-CTTT), CD 71-72 (+A), IVS2-654 (CT), poly A(A-G), 100-kb Ggamma(Agammadeltabeta) degrees and 45-kb Filipino deletions. The 192 beta-alleles studied comprised Chinese (151 patients), Malay (21), Orang Asli from East Malaysia (15), Filipino (1), Indian (1), Indonesian Chinese (2), and Thai (1). In the Chinese, 2 beta-globin defects at CD 41/42 and IVS2-654 were responsible for 74% of beta-thalassemia. beta-mutations at CD 19, IVS1-1 (G-T), IVS1-5, poly A, and hemoglobin E caused 76% of the hemoglobin disorders in the Malays. The Filipino 45-kb deletion caused 73.3% of bthalassemia in the Orang Asli. Using genomic sequencing, the rare Chinese beta-mutation at CD 43 (G-T) was confirmed in 2 Chinese, and the Mediterranean mutation IVS1-1 (G-A) was observed in a Malay beta-thalassemia carrier. The beta-globin mutations confirmed in this prenatal diagnosis study were heterogenous and 65 (68%) couples showed a different globin defect from each other. The use of specific molecular protocols has allowed rapid and successful prenatal diagnosis of beta-thalassemia in Malaysia.
Pharmacokinetics and Bioequivalence Study of a New Branded Generic Moxifloxacin Tablet Among Healthy Volunteers

Amran A, Tan CY, Tan KL, Ho RM, Anand AK, Leong CW

Clin Pharmacol Drug Dev, 2021 12;10(12):1514-1518.
PMID: 34107173 DOI: 10.1002/cpdd.964

A newly developed branded generic of a moxifloxacin (MOX) 400-mg tablet formulation was manufactured prior to this study. A bioequivalence (BE) study was done to assess the pharmacokinetics of the formulation using a randomized, open-label, 2-period crossover, 2-sequence, and single-dose experiment. Thirty healthy male volunteers were recruited. The test formulation, Flonoxin 400 mg, was compared with the reference formulation, Avelox 400 mg. The pharmacokinetic parameters of MOX were calculated based on the plasma drug concentration-time profile. Noncompartmental analysis was performed to determine its safety and tolerability. The 90% confidence intervals (CIs) were 88.5%-104.6%, 96.1%-101.1%, and 96.8%-100.7% for Cmax , AUC0-t , and AUC0-inf , respectively. All CIs were within the 80.0%-125.0% boundary, thus fulfilling the acceptable BE criteria according to the ASEAN guidelines.
Is kratom (Mitragyna speciosa Korth.) use associated with ECG abnormalities? Electrocardiogram comparisons between regular kratom users and controls

Leong Abdullah MFI, Tan KL, Narayanan S, Yuvashnee N, Chear NJY, Singh D, et al.

Clin Toxicol (Phila), 2021 May;59(5):400-408.
PMID: 32870119 DOI: 10.1080/15563650.2020.1812627

OBJECTIVES: Little is known about the cardiotoxic effects of kratom (Mitragyna speciosa Korth.), a medicinal plant. This analytical cross-sectional study investigated the prevalence of electrocardiogram (ECG) abnormalities and QTc intervals in regular kratom users compared with non-kratom-using control subjects.
METHODS: We enrolled regular kratom users and non-kratom-using control subjects from three communities. Demographic data, clinical data, kratom use characteristics, and ECG findings were recorded. The mitragynine content of kratom juice was quantified using a validated gas chromatography-mass spectrometry (GC-MS) method.
RESULTS: A total of 200 participants (100 kratom users and 100 control subjects) participated in this study. The prevalence of ECG abnormalities in kratom users (28%) did not differ from that of control subjects (32%). Kratom use was not associated with ECG abnormalities, except for significantly higher odds of sinus tachycardia (OR = 8.61, 95% CI = 1.06-70.17, p = 0.035) among kratom users compared with control subjects. The odds of observing borderline QTc intervals were significantly higher for kratom users compared with control subjects, regardless of the age of first use, the duration of use, the daily quantity consumed, and the length of time that had elapsed between last kratom use and ECG assessment. Nevertheless, there were no differences in the odds of having prolonged QTc intervals between kratom users and controls. The estimated average daily intake of mitragynine consumed by kratom users was 434.28 mg.
CONCLUSION: We found no link between regular kratom use and electrocardiographic abnormalities with an estimated average daily intake of 434.28 mg of mitragynine.
Alpha-thalassaemia in association with beta-thalassaemia patients in Malaysia: a study on the co-inheritance of both disorders

Wee YC, Tan KL, Kuldip K, Tai KS, George E, Tan PC, et al.

Community Genet, 2008;11(3):129-34.
PMID: 18376108 DOI: 10.1159/000113874

BACKGROUND/AIMS: Individuals with double heterozygosity for alpha- and beta-thalassaemia and heterozygous beta-thalassaemia show a similar haematological picture. Co-inheritance of alpha- and beta-thalassaemia in both partners may result in pregnancies with either Hb Bart's hydrops foetalis or beta-thalassaemia major, or pregnancies with both disorders.
METHODS: The co-inheritance of alpha-thalassaemia in 322 beta-thalassaemia carriers in Malaysia was studied.
RESULTS: The frequency of alpha-thalassaemia in the beta-thalassaemia carriers was 12.7% (41/322), with a carrier frequency of 7.8% for the SEA deletion, 3.7% for the -alpha(3.7) deletion, 0.9% for Hb Constant Spring and 0.3% for the -alpha(4.2) deletion.
CONCLUSION: Double heterozygosity for alpha- and beta-thalassaemia was confirmed in 5 out of the 41 couples and the risk of the fatal condition Hb Bart's hydrops foetalis was confirmed in two of these couples. Detection of the Southeast Asian (SEA) deletion in the Malaysian Malays in this study confirms that Hb Bart's hydrops foetalis can occur in this ethnic group. Results of this study have provided new information on the frequency and different types of alpha-thalassaemia (--(SEA), -alpha(3.7) and -alpha(4.2) deletions, Hb Constant Spring) in Malaysian beta-thalassaemia carriers.
Classification of suprabullar pneumatization according to the skull base attachment of the second lamella

Tan KL, Lee WH, Kim JW

Eur Arch Otorhinolaryngol, 2017 Jan;274(1):223-229.
PMID: 27423641 DOI: 10.1007/s00405-016-4201-4

The skull base attachment of the second lamella and suprabullar pneumatization are likely to be consistent landmarks if they are systematically classified. This study aimed to classify the pneumatization pattern according to the second lamella skull base attachment. A total of 202 computed tomography sides of 101 patients who underwent endoscopic sinus surgery were studied. Suprabullar pneumatization was defined as air cells present above the ethmoid bulla between the second and third lamellae. Its pattern was classified according to the air cell number and location as in the frontal cell classification. Type 0 suprabullar pneumatization was defined as no air cells between the ethmoid bulla and skull base; type 1, as a single suprabullar cell; and type 2, as multiple suprabullar cells above the ethmoid bulla. In type 3 pneumatization, the second lamella extended into the frontal sinus forming a frontal bullar cell. Type 2 was the most prevalent (40.1 %), followed by types 1, 3, and 0 (24.3, 23.3, and 12.4 %, respectively). The distance between the second lamella and anterior ethmoid artery was 8.93, 8.30, 8.50, and 11.25 mm in types 0, 1, 2, and 3 pneumatization, respectively. No patients had intraoperative injuries in the anterior ethmoid artery or lateral lamella. The second lamella skull base attachment and suprabullar pneumatization pattern could be systematically classified and be a consistent landmark to identify the frontal sinus opening.

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