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Tunku Kamarul Zaman

Department of Orthopaedic Surgery, Faculty of Medicine Building, University of Malaya, 50603 Kuala Lumpur, MALAYSIA
tkzrea@um.edu.my
He is by profession an orthopaedic surgeon with special interest in upper limb and
microsurgey and his research interest ranges from biomechanics to cell biology, and
fundamental research involving cartilage biology and stem cell applications

Journal articles

2012
Pan-Pan Chong, Lakshmi Selvaratnam, Azlina A Abbas, Tunku Kamarul (2012)  Human peripheral blood derived mesenchymal stem cells demonstrate similar characteristics and chondrogenic differentiation potential to bone marrow derived mesenchymal stem cells.   J Orthop Res 30: 4. 634-642 Apr  
Abstract: The use of mesenchymal stem cells (MSCs) for cartilage repair has generated much interest owing to their multipotentiality. However, their significant presence in peripheral blood (PB) has been a matter of much debate. The objectives of this study are to isolate and characterize MSCs derived from PB and, compare their chondrogenic potential to MSC derived from bone marrow (BM). PB and BM derived MSCs from 20 patients were isolated and characterized. From 2 ml of PB and BM, 5.4 ± 0.6 million and 10.5 ± 0.8 million adherent cells, respectively, were obtained by cell cultures at passage 2. Both PB and BM derived MSCs were able to undergo tri-lineage differentiation and showed negative expression of CD34 and CD45, but positively expressed CD105, CD166, and CD29. Qualitative and quantitative examinations on the chondrogenic potential of PB and BM derived MSCs expressed similar cartilage specific gene (COMP) and proteoglycan levels, respectively. Furthermore, the s-GAG levels expressed by chondrogenic MSCs in cultures were similar to that of native chondrocytes. In conclusion, this study demonstrates that MSCs from PB maintain similar characteristics and have similar chondrogenic differentiation potential to those derived from BM, while producing comparable s-GAG expressions to chondrocytes.
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Liang Xin Tay, Raja Elina Ahmad, Havva Dashtdar, K W Tay, T Masjuddin, S Ab-Rahim, Pan Pan Chong, L Selvaratnam, T Kamarul (2012)  Treatment outcomes of alginate-embedded allogenic mesenchymal stem cells versus autologous chondrocytes for the repair of focal articular cartilage defects in a rabbit model.   Am J Sports Med 40: 1. 83-90 Jan  
Abstract: Mesenchymal stem cells (MSCs) represent a promising alternative form of cell-based therapy for cartilage injury. However, the capacity of MSCs for chondrogenesis has not been fully explored. In particular, there is presently a lack of studies comparing the effectiveness of MSCs to conventional autologous chondrocyte (autoC) treatment for regeneration of full-thickness cartilage defects in vivo.
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Sik-Loo Tan, Raja Elina Ahmad, Tunku Sara Ahmad, Azhar M Merican, Azlina A Abbas, Wuey Min Ng, Tunku Kamarul (2012)  Effect of Growth Differentiation Factor 5 on the Proliferation and Tenogenic Differentiation Potential of Human Mesenchymal Stem Cells in vitro.   Cells Tissues Organs May  
Abstract: The use of growth differentiation factor 5 (GDF-5) in damaged tendons has been shown to improve tendon repair. It has been hypothesized that further improvements may be achieved when GDF-5 is used to promote cell proliferation and induce tenogenic differentiation in human bone marrow-derived mesenchymal stem cells (hMSCs). However, the optimal conditions required to produce these effects on hMSCs have not been demonstrated in previous studies. A study to determine cell proliferation and tenogenic differentiation in hMSCs exposed to different concentrations of GDF-5 (0, 5, 25, 50, 100 and 500 ng/ml) was thus conducted. No significant changes were observed in the cell proliferation rate in hMSCs treated at different concentrations of GDF-5. GDF-5 appeared to induce tenogenic differentiation at 100 ng/ml, as reflected by (1) a significant increase in total collagen expression, similar to that of the primary native human tenocyte culture; (2) a significant upregulation in candidate tenogenic marker gene expression, i.e. scleraxis, tenascin-C and type-I collagen; (3) the ratio of type-I collagen to type-III collagen expression was elevated to levels similar to that of human tenocyte cultures, and (4) a significant downregulation of the non-tenogenic marker genes runt-related transcription factor 2 and sex determining region Y (SRY)-box 9 at day 7 of GDF-5 induction, further excluding hMSC differentiation into other lineages. In conclusion, GDF-5 does not alter the proliferation rates of hMSCs, but, instead, induces an optimal tenogenic differentiation response at 100 ng/ml.
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R Afshar, T S Fong, M Hadi Latifi, S R Kanthan, T Kamarul (2012)  A biomechanical study comparing plate fixation using unicortical and bicortical screws in transverse metacarpal fracture models subjected to cyclic loading.   J Hand Surg Eur Vol 37: 5. 396-401 Jun  
Abstract: The use of bicortical screws to fix metacarpal fractures has been suggested to provide no added biomechanical advantage over unicortical screw fixation. However, this was only demonstrated in static loading regimes, which may not be representative of biological conditions. The present study was done to determine whether similar outcomes are obtained when cyclic loading is applied. Transverse midshaft osteotomies were created in 20 metacarpals harvested from three cadavers. Fractures were stabilised using 2.0 mm mini fragment plates fixed with either bicortical or unicortical screw fixation. These fixations were tested to failure with a three-point bending cyclic loading protocol using an electromechanical microtester and a 1 kN load cell. The mean load to failure was 370 N (SD 116) for unicortical fixation and 450 N (SD 135) for bicortical fixation. Significant differences between these two constructs were observed. A biomechanical advantage was found when using bicortical screws in metacarpal fracture plating.
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M G Hossain, R Zyroul, B P Pereira, T Kamarul (2012)  Multiple regression analysis of factors influencing dominant hand grip strength in an adult Malaysian population.   J Hand Surg Eur Vol 37: 1. 65-70 Jan  
Abstract: Grip strength is an important measure used to monitor the progression of a condition, and to evaluate outcomes of treatment. We assessed how various physical and social factors predict normal grip strength in an adult Malaysian population of mixed Asian ethnicity (254 men, 246 women). Grip strength was recorded using the Jamar dynamometer. The mean grip strength for the dominant hand was 29.8 kg for men and 17.6 kg for women. Multiple regression analysis demonstrated that the dominant hand grip strength was positively associated with height and body mass index, and negatively associated with age for both sexes. Dominant hand grip strength was related to work status for men (p < 0.05) but not for women. However, there was no difference in grip strength among ethnic groups.
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Hadi Latifi, Shanmugam Rukmanikanthan, Azura Mansor, Tunku Kamarul, Mehmet Bilgen (2012)  Prospects of implant with locking plate in fixation of subtrochanteric fracture: experimental demonstration of its potential benefits on synthetic femur model with supportive hierarchical nonlinear hyperelastic finite element analysis.   Biomed Eng Online 11: 1. Apr  
Abstract: ABSTRACT: BACKGROUND: Effective fixation of fracture requires careful selection of a suitable implant to provide stability and durability. Implant with a feature of locking plate (LP) has been used widely for treating distal fractures in femur because of its favourable clinical outcome, but its potential in fixing proximal fractures in the subtrochancteric region has yet to be explored. Therefore, this comparative study was undertaken to demonstrate the merits of the LP implant in treating the subtrochancteric fractures by comparing its performance limits against those obtained with the more traditional implants; angle blade plate (ABP) and dynamic condylar screw plate (DCSP). Materials and Methods: Nine standard composite femurs were acquired, divided into three groups and fixed with LP (n=3), ABP (n=3)and DCSP (n=3). The fracture was modeled by a 20 mm gap created at the subtrochanteric region to experimentally study the biomechanical response of each implant under axial static and dynamic loading paradigms. To confirm the experimental findings and to understand the critical interactions at the boundaries, the synthetic femur/implant systems were numerically analyzed by constructing hierarchical finite element models with nonlinear hyperelastic properties. The predictions from the analyses were then compared against the experimental measurements to demonstrate the validity of the numeric model, and to characterize the internal load distribution in the femur and load bearing properties of each implant. RESULTS: The average measurements indicated that the constructs with ABP, DCPS and LP respectively had overall stiffness values of 70.9, 110.2 and 131.4 N/mm, and exhibited reversible deformations of 12.4, 4.9 and 4.1 mm when the applied dynamic load was 400 N and plastic deformations of 11.3, 2.4 and 1.4 mm when the load was 1000 N. The corresponding peak cyclic loads to failure were 1100, 1167 and 1600 N. The errors between the displacements measured experimentally or predicted by the nonlinear hierarchical hyperelastic model were less than 18 %. In the implanted femur heads, the principal stresses were spatially heterogeneous for ABP and DCSP but more homogenous for LP, meaning LP had lower stress concentration. CONCLUSION: When fixed with the LP implant, the synthetic femur model of the subtrochancteric fracture consistently exceeds in the key biomechanical measures of stability and durability. These capabilities suggest increased resistance to fatigue and failure, which are highly desirable features expected of implants make the LP implant potentially a viable alternative to the conventional ABP or DCSP in the treatment of the subtrochancteric femur fractures for the betterment of the clinical outcome.
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M N Bajuri, Mohammed Rafiq Abdul Kadir, Murali Malliga Raman, T Kamarul (2012)  Mechanical and functional assessment of the wrist affected by rheumatoid arthritis: A finite element analysis.   Med Eng Phys Jan  
Abstract: Understanding the pathomechanics involved in rheumatoid arthritis (RA) of the wrist provides valuable information, which will invariably allow various therapeutic possibilities to be explored. The computational modelling of this disease permits the appropriate simulation to be conducted seamlessly. A study that underpins the fundamental concept that produces the biomechanical changes in a rheumatoid wrist was thus conducted through the use of finite element method. The RA model was constructed from computed tomography datasets, taking into account three major characteristics: synovial proliferation, cartilage destruction and ligamentous laxity. As control, a healthy wrist joint model was developed in parallel and compared. Cartilage was modelled based on the shape of the articulation while the ligaments were modelled with linear spring elements. A load-controlled analysis was performed simulating physiological hand grip loading conditions. The results demonstrated that the diseased model produced abnormal wrist extension and stress distribution as compared to the healthy wrist model. Due to the weakening of the ligaments, destruction of the cartilage and lower bone density, the altered biomechanical stresses were particularly evident at the radioscaphoid and capitolunate articulations which correlate to clinical findings. These results demonstrate the robust finding of the developed RA wrist model, which accurately predicted the pathological process.
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M G Hossain, P Bharati, Saw Aik, Pete E Lestrel, Almasri Abeer, T Kamarul (2012)  Body mass index of married bangladeshi women: trends and association with socio-demographic factors.   J Biosoc Sci 44: 4. 385-399 Jul  
Abstract: SummaryBody mass index (BMI) is a good indicator of nutritional status in a population. In underdeveloped countries like Bangladesh, this indicator provides a method that can assist intervention to help eradicate many preventable diseases. This study aimed to report on changes in the BMI of married Bangladeshi women who were born in the past three decades and its association with socio-demographic factors. Data for 10,115 married and currently non-pregnant Bangladeshi women were extracted from the 2007 Bangladesh Demographic and Health Survey (BDHS). The age range of the sample was 15-49 years. The mean BMI was 20.85±3.66 kg/m2, and a decreasing tendency in BMI was found among birth year cohorts from 1972 to 1992. It was found that the proportion of underweight females has been increasing in those born during the last 20 years of the study period (1972 to 1992). Body mass index increased with increasing age, education level of the woman and her husband, wealth index, age at first marriage and age at first delivery, and decreased with increasing number of ever-born children. Lower BMI was especially pronounced among women who were living in rural areas, non-Muslims, employed women, women not living with their husbands (separated) or those who had delivered at home or non-Caesarean delivery.
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Raja Mohd Aizat Raja Izaham, Mohammed Rafiq Abdul Kadir, Abdul Halim Abdul Rashid, Md Golam Hossain, T Kamarul (2012)  Finite element analysis of Puddu and Tomofix plate fixation for open wedge high tibial osteotomy.   Injury 43: 6. 898-902 Jun  
Abstract: The use of open wedge high tibial osteotomy (HTO) to correct varus deformity of the knee is well established. However, the stability of the various implants used in this procedure has not been previously demonstrated. In this study, the two most common types of plates were analysed (1) the Puddu plates that use the dynamic compression plate (DCP) concept, and (2) the Tomofix plate that uses the locking compression plate (LCP) concept. Three dimensional model of the tibia was reconstructed from computed tomography images obtained from the Medical Implant Technology Group datasets. Osteotomy and fixation models were simulated through computational processing. Simulated loading was applied at 60:40 ratios on the medial:lateral aspect during single limb stance. The model was fixed distally in all degrees of freedom. Simulated data generated from the micromotions, displacement and, implant stress were captured. At the prescribed loads, a higher displacement of 3.25mm was observed for the Puddu plate model (p<0.001). Coincidentally the amount of stresses subjected to this plate, 24.7MPa, was also significantly lower (p<0.001). There was significant negative correlation (p<0.001) between implant stresses to that of the amount of fracture displacement which signifies a less stable fixation using Puddu plates. In conclusion, this study demonstrates that the Tomofix plate produces superior stability for bony fixation in HTO procedures.
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2011
M G Hossain, A Saw, F Ohtsuki, P E Lestrel, T Kamarul (2011)  Change in facial shape in two cohorts of Japanese adult female students twenty years apart.   Singapore Med J 52: 11. 818-823 Nov  
Abstract: Introduction: Secular changes in the head and body dimensions of the Japanese population were recorded during the last century, but studies on Japanese adult facial shape were poorly documented. This study aimed to document the secular changes in facial shape and their association with craniofacial measures of Japanese adult female students. Methods: Data were collected from 1998-2001 and 1975-1979 from institutions in Tokyo and Kyoto. The prosopic index (PI) was derived from morphological facial height (n-gn) and bizygomatic breadth (zy-zy). Multiple regression analysis was used to determine the association between PI (facial form) and craniofacial measures. Results: Larger mean values for morphological facial height (n-gn) and for PI, but smaller values for bizygomatic breadth (zy-zy) and bigonial breadth (go-go) were observed in the current sample compared to their predecessors 21 years ago. The most prevalent facial shapes were mesoprosopic (30.53 percent) and euryprosopic (45.14 percent) for the current and previous series, respectively. There was a significant positive relationship between the PI and head length (g-op) (p less than 0.01), head breadth (eu-eu) (p less than 0.01) and head height (v-po) (p less than 0.05), and a negative relationship between the PI and head circumference (g-g) (p less than 0.01) and minimum frontal breadth (ft-ft) (p less than 0.01). Conclusion: Our results suggest that a narrowing of facial shape has been occurring for approximately 21 years in adult Japanese females. The best predictor variables for PI were head length, head circumference, head breadth, minimum frontal breadth and head height.
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Havva Dashtdar, Hussin A Rothan, Terence Tay, Raja Elina Ahmad, Razif Ali, Liang Xin Tay, Pan Pan Chong, Tunku Kamarul (2011)  A preliminary study comparing the use of allogenic chondrogenic pre-differentiated and undifferentiated mesenchymal stem cells for the repair of full thickness articular cartilage defects in rabbits.   J Orthop Res 29: 9. 1336-1342 Sep  
Abstract: Chondrogenic differentiated mesenchymal stem cells (CMSCs) have been shown to produce superior chondrogenic expression markers in vitro. However, the use of these cells in vivo has not been fully explored. In this study, in vivo assessment of cartilage repair potential between allogenic-derived chondrogenic pre-differentiated mesenchymal stem cells and undifferentiated MSCs (MSCs) were compared. Bilateral full thickness cartilage defects were created on the medial femoral condyles of 12 rabbits (n = 12). Rabbits were divided into two groups. In one group, the defects in the right knees were repaired using alginate encapsulated MSCs while in the second group, CMSCs were used. The animals were sacrificed and the repaired and control knees were assessed at 3 and 6 months after implantation. Quantitative analysis was performed by measuring the Glycosaminoglycans (GAGs)/total protein content. The mean Brittberg score was higher in the transplanted knees as compared to the untreated knee at 6 months (p < 0.05). Quantitative analysis of GAGs was consistent with these results. Histological and immunohistochemical analysis demonstrated hyaline-like cartilage regeneration in the transplanted sites. Significant differences between the histological scores based on O'Driscoll histological grading were observed between contralateral knees at both 3 and 6 months (p < 0.05). No significant differences were observed between the Britberg, O'Driscoll scores, and GAGs/total protein content when comparing defect sites treated with MSC and CMSC (p > 0.05). This study demonstrates that the use of either MSC or CMSC produced superior healing when compared to cartilage defects that were untreated. However, both cells produced comparable treatment outcomes.
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S R Kanthan, G Kavitha, S Addi, D S K Choon, T Kamarul (2011)  Platelet-rich plasma (PRP) enhances bone healing in non-united critical-sized defects: a preliminary study involving rabbit models.   Injury 42: 8. 782-789 Aug  
Abstract: Introduction: The use of bone grafts in treating non- or delayed unions as the result of large bone loss is well established. However, despite good outcomes, the time to achieve complete union is still considerably long. To overcome this problem, the use of platelet-rich plasma (PRP) has been advocated albeit with varying success. To determine the true effectiveness of PRP in treating non-/delayed unions, a study was conducted using (n = 12) rabbit models. Methods and materials: Critical-sized defects measuring 2 cm created in the midshaft of the right rabbit tibias were stabilised using 2.7-mm small fragment plates. A spacer placed in the defects to create a delay in bone union was replaced at 3 weeks with artificial bone grafts (Coragraft (R)), with or without PRP. The operated limbs were radiographed following the defect creation and at 3, 7 and 11 weeks (at sacrifice). Bone healing and histological changes were later assessed and scored using the appropriate grading systems. Four groups were compared for quality of healing: (group-A) control group, that is, no PRP or Coragraft; (group-B) PRP; (group-C) Coragraft; and (group-D) PRP and Coragraft. Results: Group-D demonstrated the best bone healing based on radiological, histological and gross findings (Kruskall-Wallis: p < 0.05). Group-C had significantly higher scores than group-B, whilst group-A had significantly lower scores than all other groups (Mann-Whitney U: p < 0.05). Conclusion: The use of PRP with bone graft significantly improves the quality of bone healing. However, the use of PRP without bone substitute does not provide adequate repair tissue and, therefore, provides little benefit when used independently. (C) 2011 Elsevier Ltd. All rights reserved.
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N Sangeetha, R Noorzurani, T Kamarul (2011)  Comparative analysis of autologous chondrocyte implantation and other treatment modalities : a systematic review   European Journal of Orthopaedic Surgery & Traumatology 22: 2. 89-96  
Abstract: Purpose The purpose of this systematic review was to analyze and determine the effectiveness of autologous chondrocyte implantation (ACI) when compared with other treatment modalities, which includes microfracture, mosaicplasty, abrasionplasty, bone marrow–derived mesenchymal stem cell (BMSC), and matrix-assisted autologous chondrocyte implantation (MACI). Methods Literature search using online databases PubMed, Scopus, National Institute for Clinical Excellence and Cochrane controlled trial register regarding all cell-based therapies and other interventions for chondral lesions was explored. Data on clinical outcome and repair quality were analyzed. Duplicates and irrelevant articles were omitted. Result Seventeen ( n = 17) studies were included in this review. Among the four trials on ACI versus mosaicplasty, two studies showed no differences in clinical scores, one suggested similar performance while the other suggested better results in tissue quality for ACI. A systematically performed assessment comparing ACI with microfracture shows better clinical outcomes and higher tissue quality after ACI. Studies comparing ACI with MACI or BMSC demonstrated similar results. Although many of these studies had substantial flaws, on the overall, the evidence comparing ACI with other treatment modalities shows better clinical outcomes and higher tissue quality. Conclusion Despite significant differences between the methodologies employed by different researchers, we can conclude that all except two studies demonstrated ACI being the better treatment for cartilage defects. However, final conclusions regarding long-term effects are still difficult, and therefore, future studies are needed to answer the long-term effects of ACI.
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Hossain, M G Sabiruzzaman, M Islam, S Hisyam, R Z Lestrel, T P E Kamarul (2011)  Influence of anthropometric measures and socio-demographic factors on menstrual pain and irregular menstrual cycles among university students in Bangladesh   Anthropological Science 119: 3. 239-246  
Abstract: Menstrual disturbances generally affect the daily activities of young females. The aim of this study was to determine the effects of anthropometric measures and sociodemographic factors on menstrual disturbances among university students in Bangladesh. Data were collected from 995 students from Rajshahi University using a stratified sampling technique between July 2004 and May 2005. Factors influencing menstrual pain and irregular menstrual cycles were examined with multiple logistic regression analysis. Stepwise logistic regression analysis was also used to determine the most influential factors affecting menstrual disturbances. The prevalence of menstrual pain among the university students studied was very high (72.3%), while the experience of irregular menstrual cycles was very low (12.9%). Multiple logistic regressions demonstrated that menstrual pain was affected by early age at menarche, early birth order, longer length of menstrual flow and high family income. Students suffering from irregular menstrual cycles displayed a delay in menarche, longer duration of menstrual flow and larger body mass index (BMI) values. Moreover, stepwise logistic regression showed that age at menarche, birth order, duration of menstrual flow and family income were the most important factors influencing menstrual pain. Age at menarche, duration of menstrual flow and BM I were found to be the most important factors affecting irregular menstrual cycles. These results suggest that age at menarche and duration of menstrual flow are significant common factors which affect menstrual pain and irregular menstrual cycles. Consequently, menstrual disturbance can be considered as one of the major health problems of Bangladeshi university female students and requires attention.
Notes: Hossain, Md. Golam Sabiruzzaman, Md. Islam, Saima Hisyam, Raja Zyroul Lestrel, Pete E. Kamarul, Tunku
Lily Boo, Lakshmi Selvaratnam, Cheh Chin Tai, Tunku Sara Ahmad, Tunku Kamarul (2011)  Expansion and preservation of multipotentiality of rabbit bone-marrow derived mesenchymal stem cells in dextran-based microcarrier spin culture.   J Mater Sci Mater Med 22: 5. 1343-1356 May  
Abstract: The use of mesenchymal stem cells (MSCs) in tissue repair and regeneration despite their multipotentiality has been limited by their cell source quantity and decelerating proliferative yield efficiency. A study was thus undertaken to determine the feasibility of using microcarrier beads in spinner flask cultures for MSCs expansion and compared to that of conventional monolayer cultures and static microcarrier cultures. Isolation and characterization of bone marrow derived MSCs were conducted from six adult New Zealand white rabbits. Analysis of cell morphology on microcarriers and culture plates at different time points (D0, D3, D10, D14) during cell culture were performed using scanning electron microscopy and bright field microscopy. Cell proliferation rates and cell number were measured over a period of 14 days, respectively followed by post-expansion characterization. MTT proliferation assay demonstrated a 3.20 fold increase in cell proliferation rates in MSCs cultured on microcarriers in spinner flask as compared to monolayer cultures (p < 0.05). Cell counts at day 14 were higher in those seeded on stirred microcarrier cultures (6.24 ± 0.0420 cells/ml) × 10(5) as compared to monolayer cultures (0.22 ± 0.004 cells/ml) × 10(5) and static microcarrier cultures (0.20 ± 0.002 cells/ml) × 10(5). Scanning electron microscopy demonstrated an increase in cell colonization of the cells on the microcarriers in stirred cultures. Bead-expanded MSCs were successfully differentiated into osteogenic and chondrogenic lineages. This system offers an improved and efficient alternative for culturing MSCs with preservation to their phenotype and multipotentiality.
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Sik-Loo Tan, Sofiah Sulaiman, Belinda Pingguan-Murphy, L Selvaratnam, Cheh-Chin Tai, T Kamarul (2011)  Human amnion as a novel cell delivery vehicle for chondrogenic mesenchymal stem cells.   Cell Tissue Bank 12: 1. 59-70 Feb  
Abstract: This study investigates the feasibility of processed human amnion (HAM) as a substrate for chondrogenic differentiation of mesenchymal stem cells (MSCs). HAM preparations processed by air drying (AD) and freeze drying (FD) underwent histological examination and MSC seeding in chondrogenic medium for 15 days. Monolayer cultures were used as control for chondrogenic differentiation and HAMs without cell seeding were used as negative control. Qualitative observations were made using scanning electron microscopy analysis and quantitative analyses were based on the sulfated glycosaminoglycans (GAG) assays performed on day 1 and day 15. Histological examination of HAM substrates before seeding revealed a smooth surface in AD substrates, while the FD substrates exhibited a porous surface. Cell attachment to AD and FD substrates on day 15 was qualitatively comparable. GAG were significantly highly expressed in cells seeded on FD HAM substrates. This study indicates that processed HAM is a potentially valuable material as a cell-carrier for MSC differentiation.
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T Kamarul, S Ab-Rahim, M Tumin, L Selvaratnam, T S Ahmad (2011)  A preliminary study of the effects of glucosamine sulphate and chondroitin sulphate on surgically treated and untreated focal cartilage damage.   Eur Cell Mater 21: 259-71 03  
Abstract: The effects of Glucosamine Sulphate (GS) and Chondroitin Sulphate (CS) on the healing of damaged and repaired articular cartilage were investigated. This study was conducted using 18 New Zealand white rabbits as experimental models. Focal cartilage defects, surgically created in the medial femoral condyle, were either treated by means of autologous chondrocyte implantation (ACI) or left untreated as controls. Rabbits were then divided into groups which received either GS+/-CS or no pharmacotherapy. Three rabbits from each group were sacrificed at 12 and 24 weeks post-surgery. Knees dissected from rabbits were then evaluated using gross quantification of repair tissue, glycosaminoglycan (GAG) assays, immunoassays and histological assessments. It was observed that, in contrast to untreated sites, surfaces of the ACI-repaired sites appeared smooth and continuous with the surrounding native cartilage. Histological examination demonstrated a typical hyaline cartilage structure; with proteoglycans, type II collagen and GAGs being highly expressed in repair areas. The improved regeneration of these repair sites was also noted to be significant over time (6 months vs. 3 months) and in GS and GS+CS groups compared to the untreated (without pharmacotherapy) group. Combination of ACI and pharmacotherapy (with glucosamine sulphate alone/ or with chondroitin sulphate) may prove beneficial for healing of damaged cartilage, particularly in relation to focal cartilage defects.
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G Krishnamurithy, P N Shilpa, R E Ahmad, Sofiah Sulaiman, C L L Ng, T Kamarul (2011)  Human amniotic membrane as a chondrocyte carrier vehicle/substrate: in vitro study.   J Biomed Mater Res A 99: 3. 500-506 Dec  
Abstract: Human amniotic membrane (HAM) is an established biomaterial used in many clinical applications. However, its use for tissue engineering purposes has not been fully realized. A study was therefore conducted to evaluate the feasibility of using HAM as a chondrocyte substrate/carrier. HAMs were obtained from fresh human placenta and were process to produced air dried HAM (AdHAM) and freeze dried HAM (FdHAM). Rabbit chondrocytes were isolated and expanded in vitro and seeded onto these preparations. Cell proliferation, GAG expression and GAG/cell expression were measured at days 3, 6, 9, 12, 15, 21, and 28. These were compared to chondrocytes seeded onto plastic surfaces. Histological analysis and scanning electron microscopy was performed to observe cell attachment. There was significantly higher cell proliferation rates observed between AdHAM (13-51%, P=0.001) or FdHAM (18-48%, p = 0.001) to chondrocytes in monolayer. Similarly, GAG and GAG/cell expressed in AdHAM (33-82%, p = 0.001; 22-60%, p = 0.001) or FdHAM (41-81%, p = 0.001: 28-60%, p = 0.001) were significantly higher than monolayer cultures. However, no significant differences were observed in the proliferation rates (p = 0.576), GAG expression (p = 0.476) and GAG/cell expression (p = 0.135) between AdHAM and FdHAM. The histology and scanning electron microscopy assessments demonstrates good chondrocyte attachments on both HAMs. In conclusion, both AdHAM and FdHAM provide superior chondrocyte proliferation, GAG expression, and attachment than monolayer cultures making it a potential substrate/carrier for cell based cartilage therapy and transplantation.
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2010
Hossain, M D G Islam, S Aik, S A W Zaman, P E T K Lestrel (2010)  AGE AT MENARCHE OF UNIVERSITY STUDENTS IN BANGLADESH : SECULAR TRENDS AND ASSOCIATION WITH ADULT ANTHROPOMETRIC MEASURES AND SOCIO-DEMOGRAPHIC FACTORS   Journal of biosocial science 42: 5. 677-687  
Abstract: Age at menarche has been shown to be an important indicator for diseases such as breast cancer and ischaemic heart disease. The aim of the present study was to document secular trends in age at menarche and their association with anthropometric measures and socio-demographic factors in university students in Bangladesh. Data were collected from 995 students from Rajshahi University using a stratified sampling technique between July 2004 and May 2005. Trends in age at menarche were examined by linear regression analysis. Multiple regression analysis was used to assess the association of age at menarche with adult anthropometric measures and various socio-demographic factors. The mean and median age of menarche were 13.12+/-1.16 and 13.17 years, respectively, with an increasing tendency among birth-year cohorts from 1979 to 1986. Menarcheal age was negatively associated with BMI (p<0.01), but positively associated with height (p<0.05). Early menarche was especially pronounced among students from urban environments, Muslims and those with better educated mothers. Increasing age at menarche may be explained by improved nutritional status among Bangladeshi populations. Early menarche was associated with residence location at adolescence, religion and mother’s education.
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2009
Si-Yuen Lee, Barry P Pereira, N Yusof, L Selvaratnam, Zou Yu, A A Abbas, T Kamarul (2009)  Unconfined compression properties of a porous poly(vinyl alcohol)-chitosan-based hydrogel after hydration.   Acta Biomater 5: 6. 1919-1925 Jul  
Abstract: A poly(vinyl alcohol) (PVA) hydrogel composite scaffold containing N,O-carboxymethylated chitosan (NOCC) was tested to assess its potential as a scaffold for cartilage tissue engineering in a weight-bearing environment. The mechanical properties under unconfined compression for different hydration periods were investigated. The effect of supplementing PVA with NOCC (20wt.% PVA:5vol.% NOCC) produced a porosity of 43.3% and this was compared against a non-porous PVA hydrogel (20g PVA: 100ml of water, control). Under non-hydrated conditions, the porous PVA-NOCC hydrogel behaved in a similar way to the control non-porous PVA hydrogel, with similar non-linear stress-strain response under unconfined compression (0-30% strain). After 7days' hydration, the porous hydrogel demonstrated a reduced stiffness (0.002kPa, at 25% strain), resulting in a more linear stiffness relationship over a range of 0-30% strain. Poisson's ratio for the hydrated non-porous and porous hydrogels ranged between 0.73 and 1.18, and 0.76 and 1.33, respectively, suggesting a greater fluid flow when loaded. The stress relaxation function for the porous hydrogel was affected by the hydration period (from 0 to 600s); however the percentage stress relaxation regained by about 95%, after 1200s for all hydration periods assessed. No significant differences were found between the different hydration periods between the porous hydrogels and control. The calculated aggregate modulus, H(A), for the porous hydrogel reduced drastically from 10.99kPa in its non-hydrated state to about 0.001kPa after 7days' hydration, with the calculated shear modulus reducing from 30.92 to 0.14kPa, respectively. The porous PVA-NOCC hydrogel conformed to a biphasic, viscoelastic model, which has the desired properties required for any scaffold in cartilage tissue engineering.
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L Boo, S Sofiah, L Selvaratnam, CC Tai, PM Belinda, T Kamarul (2009)  A Preliminary Study of Human Amniotic Membrane as a Potential Chondrocyte Carrier   Malaysian Orthopaedic Journal 3: 2. 16-23  
Abstract: Purpose: To investigate the feasibility of using processed human amniotic membrane (HAM) to support the attachment and proliferation of chondrocytes in vitro which in turn can be utilised as a cell delivery vehicle in tissue engineering applications. Methods: Fresh HAM obtained from patients undergoing routine elective caesarean sections was harvested, processed and dried using either freeze drying (FD) or air drying (AD) methods prior to sterilisation by gamma irradiation. Isolated, processed and characterised rabbit autologous chondrocytes were seeded on processed HAM and cultured for up to three weeks. Cell attachment and proliferation were examined qualitatively using inverted brightfield microscopy. Results: Processed HAM appeared to allow cell attachment when implanted with chondrocytes. Although cells seeded on AD and FD HAM did not appear to attach as strongly as those seeded on glycerol preserved intact human amniotic membrane, these cells to be proliferated in cell culture conditions. Conclusion: Preliminary results show that processed HAM promotes chondrocyte attachment and proliferation.
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2008
T Kamarul, L Selvaratnam, T Masjuddin, S Ab-Rahim, C Ng, K Y Chan, T S Ahmad (2008)  Autologous chondrocyte transplantation in the repair of full-thickness focal cartilage damage in rabbits.   J Orthop Surg (Hong Kong) 16: 2. 230-236 Aug  
Abstract: PURPOSE:To compare the efficacy of autologous chondrocyte transplantation (ACT) versus non-operative measures for cartilage repair in rabbits. METHODS:Nine New Zealand white rabbits were used. Identical focal defects were created in the articular cartilage of both knees. One month later, the right knee was repaired via ACT, while the left knee was left untreated (control group). The quality of cartilage tissues in both knees was compared 3 months later, according to the quantitative analysis of glycosaminoglycan (GAG) in the cartilage and macroscopic examination of histology using the Brittberg/International Cartilage Research Society (ICRS) score. RESULTS:Microscopic examination showed enhanced regeneration following ACT repair. Quantification analysis revealed significantly higher cellular expression of GAG in the ACT-treated knees (1.12 vs 0.81 microgram GAGs/mg protein, p=0.008). The mean Brittberg/ICRS score was significantly higher in the treated knees (6.00 vs 1.89, p=0.007). CONCLUSION: ACT is superior to non-operative measures for repairing focal cartilage defects, as determined by favourable histological and immunohistological outcomes at the cellular level.
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S Ab-Rahim, L Selvaratnam, T Kamarul (2008)  The effect of TGF-beta1 and beta-estradiol on glycosaminoglycan and type II collagen distribution in articular chondrocyte cultures.   Cell Biol Int 32: 7. 841-847 Jul  
Abstract: Articular cartilage extracellular matrix (ECM) plays a crucial role in regulating chondrocyte functions via cell-matrix interaction, cytoskeletal organization and integrin-mediated signaling. Factors such as interleukins, basic fibroblast growth factor (bFGF), bone morphogenic proteins (BMPs) and insulin-like growth factor (IGF) have been shown to modulate the synthesis of extracellular matrix in vitro. However, the effects of TGF-beta1 and beta-estradiol in ECM regulation require further investigation, although there have been suggestions that these factors do play a positive role. To establish the role of these factors on chondrocytes derived from articular joints, a study was conducted to investigate the effects of TGF-beta1 and beta-estradiol on glycosaminoglycan secretion and type II collagen distribution (two major component of cartilage ECM in vivo). Thus, chondrocyte cultures initiated from rabbit articular cartilage were treated with 10ng/ml of TGF-beta1, 10nM of beta-estradiol or with a combination of both factors. Sulphated glycosaminoglycan (GAG) and type II collagen levels were then measured in both these culture systems. The results revealed that the synthesis of GAG and type II collagen was shown to be enhanced in the TGF-beta1 treated cultures. This increase was also noted when TGF-beta1 and beta-estradiol were both used as culture supplements. However, beta-estradiol alone did not appear to affect GAG or type II collagen deposition. There was also no difference between the amount of collagen type II and GAG being expressed when chondrocyte cultures were treated with TGF-beta1 when compared with cultures treated with combined factors. From this, we conclude that although TGF-beta1 appears to stimulate chondrocyte ECM synthesis, beta-estradiol fails to produce similar effects. The findings of this study confirm that contrary to previous claims, beta-estradiol has little or no effect on chondrocyte ECM synthesis. Furthermore, the use of TGF-beta1 may be useful in future studies looking into biological mechanisms by which ECM synthesis in chondrocyte cultures can be augmented, particularly for clinical application.
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S C Teo, J George, T Kamarul (2008)  Tubercular synovitis mimicking rheumatoid nodules.   Med J Malaysia 63: 2. 159-161 Jun  
Abstract: Tubercular tenosynovitis is an uncommon condition and usually affects the upper limb. We report a case of a patient with Systemic Lupus Erythematosus who presented with wrist swelling. The clinical findings were suggestive of rheumatoid nodules, but the radiographic finding of calcification associated with the nodules and marked erosive changes primarily of the radio-carpal joint with sparing of the metacarpal joints led the radiologist to believe that the nodules may not be rheumatoid nodules. The presence of solid and fluid nature of the nodule and hyperechoic small echogenic foci (matted rice bodies within thickened synovium) on ultrasound suggested the presence of chronic synovitis of tuberculous infection rather than rheumatoid nodule as in our case. We recommend the use of ultrasound to determine the nature of nodular swellings seen clinically in patients with arthropathy.
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2007
Kamarul, T Razif, A Elina, R Azura, C M Ky (2007)  Normal Anterior Cruciate Ligament Laxity in the Malaysian Population   Malaysian Orthopaedic Journal 1: 2. 11-16  
Abstract: A study to determine average knee laxity in the Malaysian population and how it affects daily living was conducted at the University Malaya Medical Centre between January and April 2004. Fifty two male and 76 female subjects were recruited for this study, all of whom were healthy volunteers with no ambulatory problems. Side to side knee laxity testing was performed using a KT-1000 arthrometer. Significant differences in knee laxity were noted among different races and between sexes. For instance, overall, Chinese and female study participants had higher knee laxity: (left knee, 2.17 mm (SD=1.30) and right knee was 2.88 mm (SD= 1.51)). On average, the difference between knees was 0.70 ± 1.26 mm (less than 1 mm) which is a smaller variation than reported in previous studies which suggested 3 mm. Despite finding knee laxity ranging from 0 to 8mm, no correlations were found between Lysholm, IKDC and Tegner knee outcome scores and the degree of knee laxity. No other predictors such as height, weight and age correlated with levels of knee laxity. We therefore conclude that knee laxity is a common occurrence in the normal population and is therefore not suitable as a sole predictor of knee function and should not be used as the only criteria for surgical intervention.
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2006
Chuah, U C Kamarul, T S T Ahmad (2006)  Free radial forearm flap after partial glossectomy for squamous cell carcinoma of the tongue   Journal of the Universiti Malaya Medical Centre (JUMMEC) 9: 2. 28-31  
Abstract: Squamous cell carcinoma of the tongue is a highly malignant condition and results in high mortality and morbidity in patients despite its early detection (1). Early surgical interventions have been found to reduce mortality but in many reports, tongue reconstructions using live grafts have been found to reduce normal tongue function of speech, swallow and taste. In contrast, our report using free radial forearm flap (FRFF) to reconstruct the defect left over after a radical tongue resection in a 38-year-old gentleman with oral cancer has shown promising results. This type of reconstruction has left the patient with a functional and cosmetically acceptable tongue with minimal alteration in recognizable speech.
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T Kamarul, T S Ahmad, W Y C Loh (2006)  Hand grip strength in the adult Malaysian population.   J Orthop Surg (Hong Kong) 14: 2. 172-177 Aug  
Abstract: PURPOSE: To measure the hand grip strength of Malaysians aged 18 to 65 years. METHODS: Between January and April 2003, 412 subjects (200 women and 212 men) were recruited from staff, students, and visitors of the University of Malaya Medical Centre. Socioeconomic, general health, and lifestyle data were collected from each subject using a standard questionnaire. Weight and height were measured prior to testing. Standardised positioning and instructions based on several hand grip protocols were used. Data were collected using the LIDO kinetic work set. RESULTS: 93% of the subjects were right-hand dominant and 7% were left-hand dominant. Hand grip strength was significantly correlated with hand dominance, gender, occupation, height, and weight, but not body mass index. No significant differences in grip strength were noted with regard to race or level of income. Men were stronger than women in all age-groups, with a ratio of 1.75:1. In both right- and left-hand dominant groups, the dominant hand was consistently stronger than the non-dominant side, with a ratio of 1.12:1 in the right-hand dominant group and 1.05:1 in the left-hand dominant group. The strongest hand grip strength in the right-hand dominant group occurred in the age-group of 25 to 34 years; in the left-hand dominant group it was in the age-group of 18 to 24 years. In western populations, the mean grip strength can be as much as 1.5 times greater than in the Malaysian population. CONCLUSION: Data derived from western populations cannot be applied to a comparable Malaysian population. Gender, hand dominance, age, occupation, weight, and height must be considered when establishing normal values for grip strength.
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T Kamarul, T Sara Ahmad, William Y C Loh (2006)  A novel and improved method of predicting hand grip strength in the adult Malaysian population.   Med J Malaysia 61 Suppl B: 37-44 Dec  
Abstract: Hand grip strength measurement is a recognized part of hand function assessment. The standard measurement using the Jamar dynamometer and comparing these results to the recommended normal values suggested by the manufacturers of the Jamar was questioned as these values were based on Western population. A study comparing a novel method of predicting grip strength using our software was conducted on 25 normal subjects using the LIDO kinetic workset (Group A and B ). These results were then compared against our predictive software (Group A) and the expected values supplied together with the Jamar Dynamometer (Group B). In another group, 22 normal subjects were tested using the Jamar (Group C and D) and then matched against the predicted values using their recommended chart (Group C). The last group (Group D) was tested using the Jamar but the values attained were compared to the results from our software. In group A, the predictability of our predictive method was 100% (both R & L) as compared to (R = 64%, L = 68%) in group B, (R = 27.3%, L = 59.1%) in group C and (R = 81.8%, L = 86.4%) in group D. The differences between the predictability of both methods were statistically significant. The data collected using both the Jamar and the LIDO kinetic workset correlated well to the data from our software but not to the values suggested by the manufacturers of Jamar. We conclude that our method of predicting hand grip values are superior to that suggested by the manufacturers of dynamometers. The standard reference for hand grip strength provided by the manufacturers is less accurate in predicting the grip strength of our local population.
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Lynn Azura, T Sara Ahmad, T Kamarul (2006)  A modified Blatt dorsal capsulodesis in the treatment of dynamic scapholunate instability.   Med J Malaysia 61 Suppl B: 51-54 Dec  
Abstract: We report a case of scapholunate dissociation which was initially missed and presented late. A modification of Blatt dorsal capsulodesis performed using dorsal intercarpal ligament (DICL) and extra tunnel appears not only to add to dorsal stability but also address the volar problem as well. This modification may be a better alternative to the current technique of using a single flap.
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2005
L Selvaratnam, S Abd Rahim, T Kamarul, K Y Chan, S Sureshan, R Penafort, C L L Ng (2005)  Colonies in engineered articular cartilage express superior differentiation.   Med J Malaysia 60 Suppl C: 49-52 Jul  
Abstract: In view of poor regeneration potential of the articular cartilage, in-vitro engineering of cartilage tissue offers a promising option for progressive joint disease. This study aims to develop a biologically engineered articular cartilage for autologous transplantation. The initial work involved determination of chondrocyte yield and viability, and morphological analysis. Cartilage was harvested from the knee, hip and shoulder joints of adult New Zealand white rabbits and chondrocytes were isolated by enzymatic digestion of the extra-cellular matrix before serial cultivation in DMEM/Ham's F12 media as monolayer cultures. No differences were noted in cell yield. Although chondrocytes viability was optimal (>93%) following harvest from native cartilage, their viability tended to be lowered on passaging. Chondrocytes aggregated in isogenous colonies comprising ovoid cells with intimate intracellular contacts and readily exhibited Safranin-O positive matrix; features typically associated with articular cartilage in-vivo. However, chondrocytes also existed concurrently in scattered bipolar/multipolar forms lacking Safranin-O expression. Therefore, early data demonstrated successful serial culture of adult chondrocytes with differentiated morphology seen in established chondrocyte colonies synthesizing matrix proteoglycans.
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T Kamarul, William Y C Loh (2005)  Traumatic hip dislocation in late pregnancy: a case report.   Med J Malaysia 60 Suppl C: 114-116 Jul  
Abstract: Hip dislocation in pregnancy is an uncommon injury. We report a case of traumatic hip dislocation in the third trimester of pregnancy to highlight potential problems associated with its treatment. The rationale for choosing the preferred treatment options is discussed.
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