Tunku Sara Ahmad

Hand grip strength in the adult Malaysian population.

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.

Effect of Growth Differentiation Factor 5 on the Proliferation and Tenogenic Differentiation Potential of Human Mesenchymal Stem Cells in vitro

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.

Isolation, characterization and the multi‐lineage differentiation potential of rabbit bone marrow‐derived mesenchymal stem cells

Mesenchymal stem cells (MSCs) are recognized by their plastic adherent ability, fibroblastic‐like appearance, expression of specific surface protein markers, and are defined by their ability to undergo multi‐lineage differentiation. Although rabbit bone marrow‐derived MSCs (rbMSCs) have been used extensively in previous studies especially in translational research, these cells have neither been defined morphologically and ultrastructurally, nor been compared with their counterparts in humans in their multi‐lineage differentiation ability. A study was therefore conducted to define the morphology, surface marker proteins, ultrastructure and multi‐lineage differentiation ability of rbMSCs. Herein, the primary rbMSC cultures of three adult New Zealand white rabbits (at least 4 months old) were used for three independent experiments. rbMSCs were isolated using the gradient‐centrifugation method, an established technique for human MSCs (hMSCs) isolation. Cells were characterized by phase contrast microscopy observation, transmission electron microscopy analysis, reverse transcriptase‐polymerase chain reaction (PCR) analysis, immunocytochemistry staining, flow cytometry, alamarBlue® assay, histological staining and quantitative (q)PCR analysis. The isolated plastic adherent cells were in fibroblastic spindle‐shape and possessed eccentric, irregular‐shaped nuclei as well as rich inner cytoplasmic zones similar to that of hMSCs. The rbMSCs expressed CD29, CD44, CD73, CD81, CD90 and CD166, but were negative (or dim positive) for CD34, CD45, CD117 and HLD‐DR. Despite having similar morphology and phenotypic expression, rbMSCs possessed significantly larger cell size but had a lower proliferation rate as compared with hMSCs. Using established protocols to differentiate hMSCs, rbMSCs underwent osteogenic, adipogenic and chondrogenic differentiation. Interestingly, differentiated rbMSCs demonstrated higher levels of osteogenic (Runx2) and chondrogenic (Sox9) gene expressions than that of hMSCs (P < 0.05). There was, however, no difference in the adipogenic (Pparγ) expressions between these cell types (P > 0.05). rbMSCs possess similar morphological characteristics to hMSCs, but have a higher potential for osteogenic and chondrogenic differentiation, despite having a lower cell proliferation rate than hMSCs. The characteristics reported here may be used as a comprehensive set of criteria to define or characterize rbMSCs.

Autologous chondrocyte transplantation in the repair of full-thickness focal cartilage damage in rabbits

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 μg 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.

Identification of Pathways Mediating Growth Differentiation Factor5-Induced Tenogenic Differentiation in Human Bone Marrow Stromal Cells

To date, the molecular signalling mechanisms which regulate growth factors-induced MSCs tenogenic differentiation remain largely unknown. Therefore, a study to determine the global gene expression profile of tenogenic differentiation in human bone marrow stromal cells (hMSCs) using growth differentiation factor 5 (GDF5) was conducted. Microarray analyses were conducted on hMSCs cultures supplemented with 100 ng/ml of GDF5 and compared to undifferentiated hMSCs and adult tenocytes. Results of QuantiGene® Plex assay support the use and interpretation of the inferred gene expression profiles and pathways information. From the 27,216 genes assessed, 873 genes (3.21% of the overall human transcriptome) were significantly altered during the tenogenic differentiation process (corrected p<0.05). The genes identified as potentially associated with tenogenic differentiation were ARHGAP29, CCL2, integrin alpha 8 and neurofilament medium polypeptides. These genes, were mainly associated with cytoskeleton reorganization (stress fibers formation) signaling. Pathway analysis demonstrated the potential molecular pathways involved in tenogenic differentiation were: cytoskeleton reorganization related i.e. keratin filament signaling and activin A signaling; cell adhesion related i.e. chemokine and adhesion signaling; and extracellular matrix related i.e. arachidonic acid production signaling. Further investigation using atomic force microscopy and confocal laser scanning microscopy demonstrated apparent cytoskeleton reorganization in GDF5-induced hMSCs suggesting that cytoskeleton reorganization signaling is an important event involved in tenogenic differentiation. Besides, a reduced nucleostemin expression observed suggested a lower cell proliferation rate in hMSCs undergoing tenogenic differentiation. Understanding and elucidating the tenogenic differentiation signalling pathways are important for future optimization of tenogenic hMSCs for functional tendon cell-based therapy and tissue engineering.

The Linburg-Comstock Anomaly: Incidence in Malaysians and Effect on Pinch Strength

PURPOSE To obtain epidemiologic data on the Linburg-Comstock anomaly in Malaysia and to study the effect of the anomaly on key pinch strength. METHODS We examined 292 healthy subjects (162 female and 130 male) bilaterally for the presence of the Linburg-Comstock anomaly. Each subjects key pinch strength was measured bilaterally using a pinch meter. RESULTS The Linburg-Comstock anomaly was present in 101 of the 292 subjects (35%). Sixty-five subjects (22%) had it unilaterally, and 36 subjects (6%) had it bilaterally. The anomaly was associated with superior key pinch strength. CONCLUSIONS The study provides epidemiologic data of this anomaly in Malaysia and considers its anatomical influence on key pinch strength. TYPE OF STUDY/LEVEL OF EVIDENCE Prognostic IV.

Simplifying four-strand flexor tendon repair using double-stranded suture: a comparative ex vivo study on tensile strength and bulking

We have compared a simple four-strand flexor tendon repair, the single cross-stitch locked repair using a double-stranded suture (dsSCL) against two other four-strand repairs: the Pennington modified Kessler with double-stranded suture (dsPMK); and the cruciate cross-stitch locked repair with single-stranded suture (Modified Sandow). Thirty fresh frozen cadaveric flexor digitorum profundus tendons were transected and repaired with one of the core repair techniques using identical suture material and reinforced with identical peripheral sutures. Bulking at the repair site and tendon–suture junctions was measured. The tendons were subjected to linear load-to-failure testing. Results showed no significant difference in ultimate tensile strength between the Modified Sandow (36.8 N) and dsSCL (32.6 N) whereas the dsPMK was significantly weaker (26.8 N). There were no significant differences in 2 mm gap force, stiffness or bulk between the three repairs. We concluded that the simpler dsSCL repair is comparable to the modified Sandow repair in tensile strength, stiffness and bulking.

The reconstruction of a dorsal digital defect using a reverse homodigital island flap incorporating vascularized tendon.

We describe a modification of the reverse homodigital island flap, in which a segment of lateral band of the extensor apparatus is harvested with the flap and used to reconstruct the extensor insertion to the distal phalanx.

Glomus Tumour: a retrospective review of 15 years. experience in a single institution

ABSTRACT Glomus tumours (GT), neoplasms of the glomus body comprise 4.5% of upper limb tumours. Seventy-five per cent of these occur in the hand, and most are subungual (50%). We performed a literature review and retrospective search of histopathologically confirmed GT seen from 1995 to 2009. Fifteen patients were identified, with an average age of 49.6 years. Eight were in the hand, 2 in the upper limb, 2 lower limb and 3 in the ear. Eighty-six per cent presented with pain and 50% underwent radiological investigation. Most diagnoses followed biopsy findings. Surgical excision resulted in a recurrence rate of 13%. The average time to diagnosis was 3.3 years. The average duration of symptoms was 7 to 11 years with an average of 2 to 3 consultations prediagnosis. MRI remains the most useful imaging modality (82 to 90% sensitivity). Excision biopsy is the most common treatment. Greater awareness is needed for quicker diagnosis. KEY WORDS Glomus Tumour, Presentation, Imaging, Recurrence.

Ultra-structural changes and expression of chondrogenic and hypertrophic genes during chondrogenic differentiation of mesenchymal stromal cells in alginate beads

Chondrogenic differentiation of mesenchymal stromal cells (MSCs) in the form of pellet culture and encapsulation in alginate beads has been widely used as conventional model for in vitro chondrogenesis. However, comparative characterization between differentiation, hypertrophic markers, cell adhesion molecule and ultrastructural changes during alginate and pellet culture has not been described. Hence, the present study was conducted comparing MSCs cultured in pellet and alginate beads with monolayer culture. qPCR was performed to assess the expression of chondrogenic, hypertrophic, and cell adhesion molecule genes, whereas transmission electron microscopy (TEM) was used to assess the ultrastructural changes. In addition, immunocytochemistry for Collagen type II and aggrecan and glycosaminoglycan (GAG) analysis were performed. Our results indicate that pellet and alginate bead cultures were necessary for chondrogenic differentiation of MSC. It also indicates that cultures using alginate bead demonstrated significantly higher (p < 0.05) chondrogenic but lower hypertrophic (p < 0.05) gene expressions as compared with pellet cultures. N-cadherin and N-CAM1 expression were up-regulated in second and third weeks of culture and were comparable between the alginate bead and pellet culture groups, respectively. TEM images demonstrated ultrastructural changes resembling cell death in pellet cultures. Our results indicate that using alginate beads, MSCs express higher chondrogenic but lower hypertrophic gene expression. Enhanced production of extracellular matrix and cell adhesion molecules was also observed in this group. These findings suggest that alginate bead culture may serve as a superior chondrogenic model, whereas pellet culture is more appropriate as a hypertrophic model of chondrogenesis.