MyMedR

Fulltext Safety and immunogenicity of a tetravalent dengue vaccine in healthy children aged 2-11 years in Malaysia: a randomized, placebo-controlled, Phase III study

Hss AS, Koh MT, Tan KK, Chan LG, Zhou L, Bouckenooghe A, et al.

Vaccine, 2013 Dec 2;31(49):5814-21.

PMID: 24135573 DOI: 10.1016/j.vaccine.2013.10.013

Dengue disease is a major public health problem across the Asia-Pacific region for which there is no licensed vaccine or treatment. We evaluated the safety and immunogenicity of Phase III lots of a candidate vaccine (CYD-TDV) in children in Malaysia.

Fulltext Outcomes Following Surgery for Distal Rectal Cancers: A Comparison between Laparoscopic and Open Abdomino-Perineal Resection

Tan KK, Chong CS, Tsang CB, Koh DC

Med J Malaysia, 2013 Aug;68(4):348-52.

PMID: 24145265

Oncologic outcomes following laparoscopic abdomino-perineal resection (APR) for distal rectal cancer are infrequently reported. This study aims to compare the long term outcomes between laparoscopic and open APR in distal rectal cancers.

Fulltext Extract of Scutellaria baicalensis inhibits dengue virus replication

Zandi K, Lim TH, Rahim NA, Shu MH, Teoh BT, Sam SS, et al.

BMC Complement Altern Med, 2013 Apr 29;13:91.

PMID: 23627436 DOI: 10.1186/1472-6882-13-91

BACKGROUND: Scutellaria baicalensis (S. baicalensis) is one of the traditional Chinese medicinal herbs that have been shown to possess many health benefits. In the present study, we evaluated the in vitro antiviral activity of aqueous extract of the roots of S. baicalensis against all the four dengue virus (DENV) serotypes.

METHODS: Aqueous extract of S. baicalensis was prepared by microwave energy steam evaporation method (MEGHE™), and the anti-dengue virus replication activity was evaluated using the foci forming unit reduction assay (FFURA) in Vero cells. Quantitative real-time polymerase chain reaction (qRT-PCR) assay was used to determine the actual dengue virus RNA copy number. The presence of baicalein, a flavonoid known to inhibit dengue virus replication was determined by mass spectrometry.

RESULTS: The IC(50) values for the S. baicalensis extract on Vero cells following DENV adsorption ranged from 86.59 to 95.19 μg/mL for the different DENV serotypes. The IC(50) values decreased to 56.02 to 77.41 μg/mL when cells were treated with the extract at the time of virus adsorption for the different DENV serotypes. The extract showed potent direct virucidal activity against extracellular infectious virus particles with IC(50) that ranged from 74.33 to 95.83 μg/mL for all DENV serotypes. Weak prophylactic effects with IC(50) values that ranged from 269.9 to 369.8 μg/mL were noticed when the cells were pre-treated 2 hours prior to virus inoculation. The concentration of baicalein in the S. baicalensis extract was ~1% (1.03 μg/gm dried extract).

CONCLUSIONS: Our study demonstrates the in vitro anti-dengue virus replication property of S. baicalensis against all the four DENV serotypes investigated. The extract reduced DENV infectivity and replication in Vero cells. The extract was rich in baicalein, and could be considered for potential development of anti-DENV therapeutics.

Fulltext Dengue virus type 1 clade replacement in recurring homotypic outbreaks

Teoh BT, Sam SS, Tan KK, Johari J, Shu MH, Danlami MB, et al.

BMC Evol. Biol., 2013;13:213.

PMID: 24073945 DOI: 10.1186/1471-2148-13-213

Recurring dengue outbreaks occur in cyclical pattern in most endemic countries. The recurrences of dengue virus (DENV) infection predispose the population to increased risk of contracting the severe forms of dengue. Understanding the DENV evolutionary mechanism underlying the recurring dengue outbreaks has important implications for epidemic prediction and disease control.

Fulltext Detection of dengue viruses using reverse transcription-loop-mediated isothermal amplification

Teoh BT, Sam SS, Tan KK, Johari J, Danlami MB, Hooi PS, et al.

BMC Infect Dis, 2013;13:387.

PMID: 23964963 DOI: 10.1186/1471-2334-13-387

BACKGROUND: Early and rapid detection of dengue virus (DENV) infection during the febrile period is crucial for proper patient management and prevention of disease spread. An easy to perform and highly sensitive method is needed for routine implementation especially in the resource-limited rural healthcare settings where dengue is endemic.
METHODS: A single-tube reverse transcription-loop-mediated isothermal amplification (RT-LAMP) assay with a set of nine primers was developed for the detection of all four DENV serotypes and their different genotypes. The sensitivity and specificity of the RT-LAMP were evaluated. The clinical applicability of RT-LAMP assay for detection of DENV RNA was assessed in a total of 305 sera of clinically-suspected dengue patients. The test results of RT-LAMP were statistically compared to those of quantitative reverse transcription-polymerase chain reaction (qRT-PCR), IgM- and IgG-capture enzyme-linked immunosorbent assays (ELISA).
RESULTS: Acute DENV infection was confirmed in 171 samples (n = 305); 43.3% (74/171) and 46.8% (80/171) of the samples were positive for DENV using RT-LAMP and qRT-PCR, respectively. The combination of RT-LAMP with the dengue IgM and IgG ELISA increased detection of acute DENV infection to 97.7% (167/171), in comparison to only 70.8% (121/171) when dengue IgM and IgG ELISA alone were used. The RT-LAMP assays showed high concordance (κ = 0.939) with the qRT-PCR. The RT-LAMP assay detected up to 10 copies of virus RNA within an hour but 100% reproducibility (12/12) was achieved with 100 copies. There was no cross reactivity of RT-LAMP with other closely related arboviruses.
CONCLUSION: The RT-LAMP assay developed in this study is sensitive, specific and simple to perform. The assay improved the detection of dengue when used in combination with serological methods.

Fulltext Alternanthera sessilis Red Ethyl Acetate Fraction Exhibits Antidiabetic Potential on Obese Type 2 Diabetic Rats

Tan KK, Kim KH

Evid Based Complement Alternat Med, 2013;2013:845172.

PMID: 23606892 DOI: 10.1155/2013/845172

The antidiabetic potential of Alternanthera sessilis Red was investigated using the obese type 2 diabetic rats induced by high fat diet and streptozotocin. Three fractions (hexane, ethyl acetate, and water) were obtained from the crude ethanol extract of Alternanthera sessilis Red. Alternanthera sessilis Red ethyl acetate fraction (ASEAF) was found to possess the most potent antihyperglycemic effect through oral glucose tolerance test. The ASEAF was subsequently given to the diabetic rats for two weeks. It was found that two-week administration of ASEAF reduces the fasting blood glucose level, triglyceride level, and free fatty acid level of the rats. ASEAF-treated diabetic rats showed higher pancreatic insulin content and pancreatic total superoxide dismutase activity compared to the untreated diabetic rats. Also, the insulin sensitivity indexes suggested that ASEAF ameliorates the insulin resistant state of the diabetic rats. In conclusion, ASEAF could be developed into a potential antidiabetic agent for the management of type 2 diabetes.

Fulltext Neonatal rash - a case study

Kwa SK, Sinniah D, Tan KK

Aust Fam Physician, 2012 Sep;41(9):707-9.

PMID: 22962649

An infant, aged 48 days, is brought in by her mother to her doctor because of a rash that started during the neonatal period.

Fulltext Characteristics of children hospitalized for pandemic (H1N1) 2009, Malaysia

Muhammad Ismail HI, Tan KK, Lee YL, Pau WS, Razali KA, Mohamed T, et al.

Emerg Infect Dis, 2011 Apr;17(4):708-10.

PMID: 21470467 DOI: 10.3201/eid1704.101212

To determine effects of pandemic (H1N1) 2009 on children in the tropics, we examined characteristics of children hospitalized for this disease in Malaysia. Of 1,362 children, 51 (3.7%) died, 46 of whom were in an intensive care unit. Although disease was usually mild, ≥ 1 concurrent conditions were associated with higher death rates.

Fulltext Management of isolated splenic injuries after blunt trauma: an institution's experience over 6 years

Tan KK, Chiu MT, Vijayan A

Med J Malaysia, 2010 Dec;65(4):304-6.

PMID: 21901951

Forty-two patients with traumatic blunt splenic injuries were admitted over a six year period. Vehicular-related collisions and fall from height accounted for the injuries in 38 (90.5%) of them. Eleven (26.2%) underwent immediate surgery (7 splenectomy and 4 splenorrhaphy), while the remaining 31 patients were treated nonoperatively of which 3 underwent angio-embolisation. Twenty seven patients had either grade III or IV splenic injuries. Operative management was more likely in patients with lower haemoglobin or with more severe splenic injury. Nonoperative management can be adopted in patients with blunt isolated splenic injuries but operative management is still indispensable in certain instances.

Influenza vaccine concurrently administered with a combination measles, mumps, and rubella vaccine to young children

Lum LC, Borja-Tabora CF, Breiman RF, Vesikari T, Sablan BP, Chay OM, et al.

Vaccine, 2010 Feb 10;28(6):1566-74.

PMID: 20003918 DOI: 10.1016/j.vaccine.2009.11.054

Children aged 11 to <24 months received 2 intranasal doses of live attenuated influenza vaccine (LAIV) or placebo, 35+/-7 days apart. Dose 1 was administered concomitantly with a combined measles, mumps, and rubella vaccine (Priorix). Seroresponses to measles and mumps were similar between groups. Compared with placebo, response rates to rubella in LAIV+Priorix recipients were statistically lower at a 15 IU/mL threshold (83.9% vs 78.0%) and the prespecified noninferiority criteria were not met. In a post hoc analysis using an alternate widely accepted threshold of 10 IU/mL, the noninferiority criteria were met (93.4% vs 89.8%). Concomitant administration with Priorix did not affect the overall influenza protection rate of LAIV (78.4% and 63.8% against antigenically similar influenza strains and any strain, respectively).

Importance of a thorough examination

Pau WS, Tan KK

Pediatr Infect Dis J, 2008 Jun;27(6):569-70.

PMID: 18449061 DOI: 10.1097/INF.0b013e318168db08

Scrub typhus is a common cause of febrile illness among children from rural regions in tropical countries. We described 2 cases of scrub typhus with an eschar localized in the genitalia that was missed during the routine medical examination of a febrile child.

Differential osteogenic activity of osteoprogenitor cells on HA and TCP/HA scaffold of tissue engineered bone

Ng AM, Tan KK, Phang MY, Aziyati O, Tan GH, Isa MR, et al.

J Biomed Mater Res A, 2008 May;85(2):301-12.

PMID: 17688285

Biomaterial, an essential component of tissue engineering, serves as a scaffold for cell attachment, proliferation, and differentiation; provides the three dimensional (3D) structure and, in some applications, the mechanical strength required for the engineered tissue. Both synthetic and naturally occurring calcium phosphate based biomaterial have been used as bone fillers or bone extenders in orthopedic and reconstructive surgeries. This study aims to evaluate two popular calcium phosphate based biomaterial i.e., hydroxyapatite (HA) and tricalcium phosphate/hydroxyapatite (TCP/HA) granules as scaffold materials in bone tissue engineering. In our strategy for constructing tissue engineered bone, human osteoprogenitor cells derived from periosteum were incorporated with human plasma-derived fibrin and seeded onto HA or TCP/HA forming 3D tissue constructs and further maintained in osteogenic medium for 4 weeks to induce osteogenic differentiation. Constructs were subsequently implanted intramuscularly in nude mice for 8 weeks after which mice were euthanized and constructs harvested for evaluation. The differential cell response to the biomaterial (HA or TCP/HA) adopted as scaffold was illustrated by the histology of undecalcified constructs and evaluation using SEM and TEM. Both HA and TCP/HA constructs showed evidence of cell proliferation, calcium deposition, and collagen bundle formation albeit lesser in the former. Our findings demonstrated that TCP/HA is superior between the two in early bone formation and hence is the scaffold material of choice in bone tissue engineering.

Fulltext Bone graft substitute using hydroxyapatite scaffold seeded with tissue engineered autologous osteoprogenitor cells in spinal fusion: early result in a sheep model

Tan KK, Tan GH, Shamsul BS, Chua KH, Ng MHA, Ruszymah BHI, et al.

Med J Malaysia, 2005 Jul;60 Suppl C:53-8.

PMID: 16381285

Spinal fusion using autologous bone graft is performed in an increasing rate for many spinal disorders. However, graft harvesting procedure is associated with prolonged operation time and potential donor site morbidity. We produced an engineered 'bone graft' substitute by using porous hydroxyapatite (HA) scaffold seeded with autologous bone marrow osteoprogenitor cells (OPCs) and fibrin. This obviates bone graft harvesting, thus eliminates donor site morbidity and shortens the operation time. The aim of this study is to evaluate Hydroxyapatite (HA) ceramics as scaffold for autologous tissue engineered bone construct for spinal fusion in a sheep model. The sheep's marrow was aspirated from iliac crest. The bone marrow mesenchymal stem cells (BMMSCs) were cultured for several passages in the presence of growth and differentiation factors to increase the number of OPCs. After the cultures reached confluence, they were trypsinized and seeded on Hydroxyapatite scaffold (HA). Approximately 5 million cells were generated after 3 weeks of culture. Microscopically, very tight Colony Forming Units (CFU-Fs) were seen on monolayer culture. The Von Kossa and Alizarin Red staining of monolayer culture showed positive mineralization areas; indicating the presence of OPCs. Sheep underwent a posterolateral spinal fusion in which scaffolds with or without OPCs seeded were implanted on both sides of the lumbar spine (L1-L2). Intended fusion segments were immobilized using wires. At the end of third month, the fusion constructs were harvested for histological examination. Fibrous tissue infiltration found in the inter-connecting pores of plain HA ceramics indicates inefficient new bone regeneration. New bone was found surrounding the HA ceramics seeded with autologous cells. The new bone is probably formed by the sheep BMMSCs that were initially encapsulating HA while it remained intact. The new bone is naturally fused with the vertebrae. In conclusion, the incorporation of autologous bone marrow cells improved the effectiveness of HA ceramics as 'bone graft' substitute for spinal fusion.

Fulltext Progressive supra-axial cervical instability in Down syndrome: a case report emphasising the role of extended short-segment fusion

Tan GH, Tan KK, Afian MS, Liew WF, Mohamad AR

Med J Malaysia, 2005 Jul;60 Suppl C:111-3.

PMID: 16381295

We report a case of upper cervical instability associated with Down syndrome to highlight its potential progression to inflict cord compression and the rationale for surgical decompression and extended short segment occipito-axial fusion.

Comparison of bioengineered human bone construct from four sources of osteogenic cells

Ng AM, Saim AB, Tan KK, Tan GH, Mokhtar SA, Rose IM, et al.

J Orthop Sci, 2005;10(2):192-9.

PMID: 15815868

Osteoprogenitor cells have been reported to be present in periosteum, cancellous and cortical bone, and bone marrow; but no attempt to identify the best cell source for bone tissue engineering has yet been reported. In this study, we aimed to investigate the growth and differentiation pattern of cells derived from these four sources in terms of cell doubling time and expression of osteoblast-specific markers in both monolayer cells and three-dimensional cell constructs in vitro. In parallel, human plasma derived-fibrin was evaluated for use as biomaterial when forming three-dimensional bone constructs. Our findings showed osteoprogenitor cells derived from periosteum to be most proliferative followed by cortical bone, cancellous bone, and then bone marrow aspirate. Bone-forming activity was observed in constructs formed with cells derived from periosteum, whereas calcium deposition was seen throughout the constructs formed with cells derived from cancellous and cortical bones. Although no mineralization activity was seen in constructs formed with osteoprogenitor cells derived from bone marrow, well-organized lacunae as would appear in the early phase of bone reconstruction were noted. Scanning electron microscopy evaluation showed cell proliferation throughout the fibrin matrix, suggesting the possible application of human fibrin as the bioengineered tissue scaffold at non-load-bearing sites.

Fulltext The rusty knee--pigmented villonodular synovitis

Samsudin O, Leong KK, Shukur MH, Tan KK, Ismail S

Med J Malaysia, 2004 Dec;59 Suppl F:54-6.

PMID: 15941164

Pigmented villonodular synovitis (PVNS) is a distinct but rare clinical entity often presents late with a diagnostic difficulty. Its non-specific manifestations require exclusion of several chronic inflammatory disorders and other humorous lesions but all investigations including highly predictive magnetic resonance imaging (MRI) and arthroscopic examination are non-diagnostic demanding confirmatory tissue biopsy. A typical case of such lesion is presented to highlight some potential difficulties.

Evaluation of suitable biodegradable scaffolds for engineered bone tissue

Phang MY, Ng MH, Tan KK, Aminuddin BS, Ruszymah BH, Fauziah O

Med J Malaysia, 2004 May;59 Suppl B:198-9.

PMID: 15468886

Tricalcium phosphate/hydroxyapatite (TCP/HA), hydroxyapatite (HA), chitosan and calcium sulphate (CaSO4) were studied and evaluated for possible bone tissue engineered construct acting as good support for osteogenic cells to proliferate, differentiate, and eventually spread and integrate into the scaffold. Surface morphology visualized by SEM showed that scaffold materials with additional fibrin had more cell densities attached than those without, depicting that the presence of fibrin and collagen fibers were truly a favourite choice of cells to attach. In comparison of various biomaterials used incorporated with fibrin, TCP/HA had the most cluster of cells attached.

Strategy for generating tissue-engineered human bone construct

Tan KK, Aminuddin BS, Tan GH, Sabarul Afian M, Ng MH, Fauziah O, et al.

Med J Malaysia, 2004 May;59 Suppl B:43-4.

PMID: 15468810

The strategy used to generate tissue-engineered bone construct, in view of future clinical application is presented here. Osteoprogenitor cells from periosteum of consenting scoliosis patients were isolated. Growth factors viz TGF-B2, bFGF and IGF-1 were used in concert to increase cell proliferation during in vitro cell expansion. Porous tricalcium phosphate (TCP)-hydroxyapatite (HA) scaffold was used as the scaffold to form 3D bone construct. We found that the addition of growth factors, greatly increased cell growth by 2 to 7 fold. TCP/HA proved to be the ideal scaffold for cell attachment and proliferation. Hence, this model will be further carried out on animal trial.

The use of bone marrow stem cells for bone tissue engineering

Ng MH, Aminuddin BS, Tan KK, Tan GH, Sabarul Afian M, Ruszymah BH

Med J Malaysia, 2004 May;59 Suppl B:41-2.

PMID: 15468809

Bone marrow stem cells (BMSC), known for its multipotency to differentiate into various mesenchymal cells such as chodrocyte, osteoblasts, adipocytes, etc, have been actively applied in tissue engineering. BMSC have been successfully isolated from bone marrow aspirate and bone marrow scraping from patients of various ages (13-56 years) with as little as 2ml to 5ml aspirate. BMSC isolated from our laboratory showed the presence of a heterogenous population that showed varying prevalence of surface antigens and the presence of telomerase activity albeit weak. Upon osteogenic induction, alkaline phosphatase activity and mineralization activity were observed.

Fulltext Pneumonia presenting as acute abdomen in children: a report of three cases

Vendargon S, Wong PS, Tan KK

Med J Malaysia, 2000 Dec;55(4):520-3.

PMID: 11221169

From 10th September 1998 till 5th June 1999, the Paediatric and Cardiothoracic Surgery Units of Sultanah Aminah Hospital Johor Bahru managed three children with lung collapse secondary to pneumonia. The dominant initial clinical presentation in all three cases was acute abdominal pain. Basal pneumonia was diagnosed in two cases post-operatively after surgical contributory causes were excluded intra-operatively. Thoracotomy, evacuation of infected debris and decortication of the collapsed lung was done in all three cases. In children presenting with acute abdominal pain, basal pneumonia should be considered as a possible contributory cause.

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