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Reference interval establishment of full blood count extended research parameters in the multi-ethnic population of Malaysia

Angeli A, Andrew OS, Qian YZ, Anselm ST, Chang KM, Jameela S, et al.

Med J Malaysia, 2019 12;74(6):534-536.
PMID: 31929481

Haematological cellular structures may be elucidated using automated full blood count (FBC) analysers such as Unicel DxH 800 via cell population data (CPD) analysis. The CPD values are generated by calculating volume, conductivity, and five types of scatter angles of individual cells which would form clusters or populations. This study considered 126 CPD parameter values of 1077 healthy Malaysian adults to develop reference intervals for each CPD parameter. The utility of the CPD reference interval established may range from understanding the normal haematological cellular structures to analysis of distinct cellular features related to the development of haematological disorders and malignancies.
A case report of primary hyperparathyroidism with severe bony involvement and nephrolithiasis

Chan SP, Hew FL, Jayaram G, Kumar G, Chang KW, Tay A

Ann Acad Med Singap, 2001 Jan;30(1):66-70.
PMID: 11242630

INTRODUCTION: Although the majority of patients with primary hyperparathyroidism have a relatively asymptomatic benign disorder, there are patients who have a more aggressive disorder.
CLINICAL PICTURE: We report a case of primary hyperparathyroidism presenting during pregnancy complicated by antepartum haemorrhage and severe prematurity. The diagnosis was made postpartum, when her problems rapidly progressed to result in severe neuromuscular weakness, bilateral pathological hip fractures as well as nephrolithiasis.
TREATMENT: Surgical parathyroidectomy was performed. The underlying lesion was a large solitary parathyroid adenoma with cystic elements.
CONCLUSION: Primary hyperparathyroidism is not an innocuous disease and can result in severe morbidity if left untreated.
Fulltext Daily feeding of fresh Neem leaves (Azadirachta indica) for worm control in sheep

Chandrawathani P, Chang KW, Nurulaini R, Waller PJ, Adnan M, Zaini CM, et al.

Trop Biomed, 2006 Jun;23(1):23-30.
PMID: 17041548 MyJurnal

This study was conducted to evaluate the anthelmintic effect of neem (Azadirachta indica) on nematode parasites of sheep. Twelve Santa Ines cross bred sheep from a government farm were randomly selected and equally divided into control (n = 6) and treated groups (n =6). Faecal egg counts (FEC) using the modified McMaster technique and the FAMACHA score for assessing clinical anaemia were carried out daily and recorded for 6 weeks. At the end of the study all the animals were slaughtered and the total worm count (TWC) was done. The results of FEC showed that there was no significant difference between the control and treated group (p = 0.081). However, worm burden estimations showed that the number of parasites was significantly higher in the control group compared to the treated group (p < 0.05). This result indicated that feeding Neem had an effect on worm numbers in sheep, but was not reflected in their faecal egg counts. Further work is needed to reconfirm the effect of Neem on helminth infections of sheep.
Fulltext Diagnosis and management of imported Chikungunya fever in Taiwan: a case report

Chang K, Hsieh HC, Tsai JJ, Lin WR, Lu PL, Chen YH

Kaohsiung J. Med. Sci., 2010 May;26(5):256-60.
PMID: 20466336 DOI: 10.1016/S1607-551X(10)70037-1

Chikungunya virus, a mosquito-borne alphavirus, is endemic in Africa and Southeast Asia but is rarely reported in Taiwan. We report the case of a Taiwanese woman who developed Chikungunya fever, which was first diagnosed by a clinician rather than by fever screening at an airport. The woman presented with fever, maculopapular rash, and arthralgia, the triad for the disease, on the day she returned home after a trip to Malaysia. These symptoms are very similar to those of dengue fever, which is endemic in Southern Taiwan. Chikungunya infection was confirmed by reverse transcriptase-polymerase chain reaction and seroconversion on paired serum specimens. For approximately 40 years until 2006, no cases of Chikungunya fever had been found in Taiwan. Clinicians in Taiwan should consider Chikungunya fever as a possible diagnosis for a febrile patient with arthralgia, rash, and a history of travel to an endemic area, such as Africa or Southeast Asia.
The effect of excision of the posterior arch of C1 on C1/C2 fusion using transarticular screws

Chang KC, Samartzis D, Fuego SM, Dhatt SS, Wong YW, Cheung WY, et al.

Bone Joint J, 2013 Jul;95-B(7):972-6.
PMID: 23814252 DOI: 10.1302/0301-620X.95B7.30598

Transarticular screw fixation with autograft is an established procedure for the surgical treatment of atlantoaxial instability. Removal of the posterior arch of C1 may affect the rate of fusion. This study assessed the rate of atlantoaxial fusion using transarticular screws with or without removal of the posterior arch of C1. We reviewed 30 consecutive patients who underwent atlantoaxial fusion with a minimum follow-up of two years. In 25 patients (group A) the posterior arch of C1 was not excised (group A) and in five it was (group B). Fusion was assessed on static and dynamic radiographs. In selected patients CT imaging was also used to assess fusion and the position of the screws. There were 15 men and 15 women with a mean age of 51.2 years (23 to 77) and a mean follow-up of 7.7 years (2 to 11.6). Stable union with a solid fusion or a stable fibrous union was achieved in 29 patients (97%). In Group A, 20 patients (80%) achieved a solid fusion, four (16%) a stable fibrous union and one (4%) a nonunion. In Group B, stable union was achieved in all patients, three having a solid fusion and two a stable fibrous union. There was no statistically significant difference between the status of fusion in the two groups. Complications were noted in 12 patients (40%); these were mainly related to the screws, and included malpositioning and breakage. The presence of an intact or removed posterior arch of C1 did not affect the rate of fusion in patients with atlantoaxial instability undergoing C1/C2 fusion using transarticular screws and autograft.
Fulltext National Cancer Patient Registry--Haematology Malignancy (NCPR-HM)

Chang KM, Ong TC

Med J Malaysia, 2008 Sep;63 Suppl C:66-7.
PMID: 19227675

Treatment option of Haematological malignancies has expanded over the last decade. The outcome of treatment is expected to be better compare to previously. However, study of treatment outcome for haematological malignancies has not been carried out in Malaysia. The goal of this study is to measure the treatment outcome in patients with haematological malignancy.
Fulltext Pressure ulcers--randomised controlled trial comparing hydrocolloid and saline gauze dressings

Chang KW, Alsagoff S, Ong KT, Sim PH

Med J Malaysia, 1998 Dec;53(4):428-31.
PMID: 10971989

An open comparative randomised study comparing the performance of hydrocolloid dressings (DuoDERM CGF) to saline gauze dressings in the treatment of pressure ulcers was done to evaluate the overall dressing performance, wound healing and cost effectiveness. Thirty-four subjects were enrolled at the University Hospital, Kuala Lumpur over a 643 days period. Inclusion criteria were Stage II or III pressure ulcers, at least 18 years of age and written informed consent. Only one pressure ulcer per subject was enrolled in the study. Patients with infected pressure ulcers, diabetes mellitus, an immuno-compromised status and known sensitivity to the study dressings were excluded. Subjects who met the enrollment criteria were randomised to one of the two dressing regimes. They were expected to participate in the study for a maximum of eight weeks or until the pressure ulcer healed, which ever occurred first. Overall subject age averaged 58 years and the mean duration of pressure ulcer existence was about 1 month. Twenty-one of the thirty-four ulcers enrolled were stage II and thirteen were stage III. The majority of the ulcers (88%) were located in the sacral area and seventeen subjects (50%) were incontinent. In the evaluation of dressing performance in terms of adherence to wound bed, exudate handling ability, overall comfort and pain during dressing removal; all favoured the hydrocolloid dressing by a statistically significant margin (p < 0.001). Subjects assigned the hydrocolloid dressing experienced a mean 34% reduction from their baseline surface area measurement compared to a mean 9% increase by subjects assigned gauze dressings. This was not statistically significant (p = 0.2318). In cost evaluation of the study products, there was no statistical significance in the total cost of wound management per subject. When only labour time and cost was evaluated, there was a statistically significant advantage towards hydrocolloid dressings.
Fulltext Sex differences in patients undergoing transcatheter aortic valve replacement in Asia

Chiam PTL, Hayashida K, Watanabe Y, Yin WH, Kao HL, Lee MKY, et al.

Open Heart, 2021 01;8(1).
PMID: 33419935 DOI: 10.1136/openhrt-2020-001541

OBJECTIVES: Transcatheter aortic valve replacement (TAVR) is increasingly performed. Physically small Asians have smaller aortic root and peripheral vessel anatomy. The influence of gender of Asian patients undergoing TAVR is unknown and may affect outcomes. The aim of this study was to assess sex differences in Asian patients undergoing TAVR.
METHODS: Patients undergoing TAVR from eight countries were enrolled. In this retrospective analysis, we examined differences in characteristics, 30-day clinical outcomes and 1-year survival between female and male Asian patients.
RESULTS: Eight hundred and seventy-three patients (54.4% women) were included. Women were older, smaller and had less coronary artery and lung disease but tended to have higher logistic EuroSCOREs. Smaller prostheses were used more often in women. Major vascular complications occurred more frequently in women (5.5% vs 1.8%, p<0.01); however, 30-day stroke and mortality (women vs men: 1.5% vs 1.6%, p=0.95% and 4.3% vs 3.4%, p=0.48) were similar. Functional status improvement was significant and comparable between the sexes. Conduction disturbance and permanent pacemaker requirements (11.2% vs 9.0%, p=0.52) were also similar as was 1-year survival (women vs men: 85.6% vs 88.2%, p=0.25). The only predictors of 30-day mortality were major vascular injury in women and age in men.
CONCLUSIONS: Asian women had significantly smaller stature and anatomy with some differences in clinical profiles. Despite more frequent major vascular complications, women had similar 30-day stroke or mortality rates. Functional status improvement was significant and comparable between the sexes. Conduction disturbance and permanent pacemaker requirements were similar as was 1-year survival.
Bone marrow and stem cell transplantation: Malaysian experience

Gan G, Teh A, Chan L, Cheong S, Chang K, Ibrahim H

Bone Marrow Transplant, 2008 Aug;42 Suppl 1:S103-S105.
PMID: 18724278 DOI: 10.1038/bmt.2008.129

Malaysia conducted the first BMT in the country in 1987. Since then, there have been 1155 transplantations performed in a total of eight transplant centres. A majority of the transplantations were allogeneic, including myeloablative and nonmyeloablative. A vast majority of donors are HLA identical siblings. The mean age of transplanted patients was 26 years. The major reason for transplantation was hematological malignancies. The overall survival was 60% for allogeneic transplantation and 52% for autologous transplantation. The most common cause of death in transplanted patients was the underlying disease followed by infection-related complications. Currently, the government is expanding the existing public cord blood bank as well as the local donor registry.
Tuberculous liver abscess

Goh KL, Pathmanathan R, Chang KW, Wong NW

J Trop Med Hyg, 1987 Oct;90(5):255-7.
PMID: 3669128

Tuberculous liver abscess is uncommonly seen in our experience. We report a case of a 17-year-old boy who presented with typical clinical features of liver abscess, where a diagnosis of tuberculous liver abscess was made on laparotomy and biopsy of the abscess wall.
Development of animal disease data bank in Malaysia

Jamaluddin AA, Chang KW, Johar MS, Yaacob H

Acta Vet Scand Suppl, 1988;84:194-6.
PMID: 3232606
Fulltext Thalassaemia screening among students in a secondary school in Ampang, Malaysia

Jameela S, Sabirah SO, Babam J, Phan CL, Visalachy P, Chang KM, et al.

Med J Malaysia, 2011 Dec;66(5):522-4.
PMID: 22390120 MyJurnal

Thalassaemia is a common disorder in Malaysia. It is estimated that 4.5% of the population are carriers for beta- or alpha- thalassaemias. We set out to screen Form 4 students aged between 15 and 16 years old in a national school, for thalassaemia in March 2008. Written consent was obtained from 310 students. The carrier rate for the common thalassaemia syndromes was 6.8% (2.9% for beta-thalassaemia, 2.6% for HbE and 1.3% for two-gene deletion for alpha-thalassaemia). Carriers for beta-thalassaemia and two-gene deletion for alpha-thalassaemia were more common in the Chinese (4.3% and 1.4% respectively) while heterozygous HbE was more common in the Malays (3.8%). The laboratory cost of screening one student was RM 45 and the total number of man-hours spent in this screening activity was 600. This screening exercise showed that thalassaemia carriers are common among the Chinese and Malays and it is feasible to carry out a screening programme for secondary school students.
Fulltext Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1

Klionsky DJ, Abdel-Aziz AK, Abdelfatah S, Abdellatif M, Abdoli A, Abel S, et al.

Autophagy, 2021 Jan;17(1):1-382.
PMID: 33634751 DOI: 10.1080/15548627.2020.1797280

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
Carcinoma in multinodular goitre

Koh KB, Chang KW

Br J Surg, 1992 Mar;79(3):266-7.
PMID: 1555099

A retrospective review of 107 patients operated on for multinodular goitre was carried out to determine the incidence of carcinoma. Of the group 7.5 per cent harboured incidental carcinomas with papillary carcinoma being the most common variety. The indications for removal of multinodular goitre should be compressive symptoms, suspicion of malignancy and cosmesis.
Fulltext Effect of H2 antagonists on outcome of simple closure for perforated duodenal ulcer

Koh KB, Chang KW

Singapore Med J, 1992 Oct;33(5):472-3.
PMID: 1360708

The treatment of perforated duodenal ulcer is controversial. Since the advent of H2 antagonists, the number of ulcer operations has declined tremendously. We wanted to find out if the addition of a H2 antagonist after simple closure of a perforated duodenal ulcer would change the outcome and therefore reviewed 46 patients treated in this fashion. Our results show that this is a safe and effective way of treating patients with perforated duodenal ulcer.
Fluctuation of BCR-ABL1 qPCRIS level beyond 0.1%IS after stopping tyrosine kinase inhibitor in chronic myeloid leukaemia patients with deep molecular response for at least two years

Kuan JW, Chang KM, Phan CL, Wong SP, Lim SM, Toh SG, et al.

Med J Malaysia, 2021 May;76(3):414-416.
PMID: 34031342

Fluctuation of BCR-ABL1 real-time quantitative polymerase chain reaction in International Scale (qPCRIS) level below major molecular response (MMR) (0.1%IS) is a known phenomenon after stopping tyrosine kinase inhibitor (TKI) in chronic myeloid leukaemia (CML) patients who are attempting treatment free remission (TFR). We report here four cases of fluctuation beyond MMR during conduct of a Malaysia Stop TKI Trial (MSIT) to examine the validity of the commonly used relapse criterion - loss of MMR for one reading - aiming to provide evidence in setting relapse criteria for future CML patients who want to attempt TFR.
Selection of reference genes for quantitative studies in acute myeloid leukaemia

Lee C, Yiau KXS, Lee LJ, Chong PP, Chang KM, Abdullah M

Malays J Pathol, 2019 Dec;41(3):313-326.
PMID: 31901916

INTRODUCTION: Quantitative polymerase chain reaction (qPCR) is commonly used in the investigation of acute myeloid leukaemias (AML). Stable reference genes (RG) are essential for accurate and reliable reporting but no standard method for selection has been endorsed.
MATERIALS AND METHODS: We evaluated simple statistics and published model-based approaches. Multiplex-qPCR was conducted to determine the expression of 24 candidate RG in AMLs (N=9). Singleplex-qPCR was carried out on selected RG (SRP14, B2M and ATP5B) and genes of interest in AML (N=15) and healthy controls, HC (N=12).
RESULTS: RG expression levels in AML samples were highly variable and coefficient of variance (CV) ranged from 0.37% to 10.17%. Analysis using GeNorm and Normfinder listed different orders of most stable genes but the top seven (ACTB, UBE2D2, B2M, NF45, RPL37A, GK, QARS) were the same. In singleplex-qPCR, SRP14 maintained the lowest CV in AML samples. B2M, one of most stable reference genes in AML, was expressed near significantly different in AML and HC. GeNorm selected ATP5B+SRP14 while Normfinder chose SRP14+B2M as the best two RG in combination. The median expressions of combined RG genes in AML compared to HC were less significantly different than individually implying smaller expression variation after combination. Genes of interest normalised with RG in combination or individually, displayed significantly different expression patterns.
CONCLUSIONS: The selection of best reference gene in qPCR must consider all sample sets. Model-based approaches are important in large candidate gene analysis. This study showed combination of RG SRP14+B2M was the most suitable normalisation factor for qPCR analysis of AML and healthy individuals.
Fulltext Intestinal lymphangiectasia--a report of three Chinese children in Malaysia

Lee WS, Boey CC, Goh AY, Chang KW, Iyngkaran N

Singapore Med J, 1998 Sep;39(9):418-21.
PMID: 9885723

This is a report of 3 Chinese children with intestinal lymphangiectasia in Malaysia. Two children responded to a low fat diet and medium-chain triglyceride supplement. The third child has recurrent chylous ascites. None of the children has recurrent infections despite low CD4+ cells and low levels of IgG and IgA. Intestinal lymphangiectasia is a rare congenital disorder of the mesenteric lymphatic that leads to the obstruction of the lymphatics of the intestine and protein losing enteropathy. Restriction of dietary fat intake will usually result in remission. Recurrent chylous ascites is a problem and management can be difficult.
Fulltext Meconium ileus--a rare cause of neonatal intestinal obstruction in Malaysia

Lim CT, Yip CH, Chang KW

Singapore Med J, 1994 Feb;35(1):74-6.
PMID: 8009287

Meconium ileus, rare in Malaysia, accounts for 3.7% of all neonatal intestinal obstructions (excluding imperforate anus) seen in the University Hospital, Kuala Lumpur, from 1980-1990. This paper retrospectively reviews our clinical experience with 5 cases of meconium ileus seen over a 12-year period from 1980-1991 in the University Hospital, Kuala Lumpur. Three of the neonates were Malays, and two were Punjabis. Four of them were full-term and one preterm. The birth weights ranged from 1900 to 3700 g, with a mean of 2670 g. One of them also had a sibling with meconium ileus. Two of them were found to have foetal ascites and one had intestinal obstruction, antenatally by ultrasonography. The remaining two were symptomatic soon after birth. Extensive calcification was observed on plain abdominal radiographs in three babies and dilated bowels in the other two. All of them underwent laparotomy and uncomplicated meconium ileus was confirmed in two cases, meconium peritonitis in two and one meconium pseudocyst in addition to meconium peritonitis. There was one intraoperative death, and one long-term survivor who did not have cystic fibrosis. The remaining three did not have additional features suggestive of cystic fibrosis, and finally succumbed to respiratory infection. Sweat test was not done to confirm the diagnosis for logistic reasons. The management of such patients proved to be a challenge to clinicians because of the rarity of this condition.
Fulltext Modulating multidrug resistance gene in leukaemia cells by short interfering RNA

Lim MN, Lau NS, Chang KM, Leong CF, Zakaria Z

Singapore Med J, 2007 Oct;48(10):932-8.
PMID: 17909680

The multidrug resistance gene, MDR1, is one of the genes responsible for resistance to chemotherapy in the treatment of leukaemia and other cancers. The discovery of RNA interference in mammalian cells has provided a powerful tool to inhibit the expression of this gene. However, very little is known about the transfection of leukaemia cells with short interfering RNA (siRNA) targeted at MDR1. This study aims to evaluate the effectiveness of two chemically-synthesised siRNA in modulating MDR1 gene and inhibiting P-glycoprotein expression in leukaemic cells. We also evaluated two siRNA delivery methods in this study.

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