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  1. Fulltext Morphological study of the newly designed cementless femoral stem
    Baharuddin MY, Salleh ShH, Zulkifly AH, Lee MH, Mohd Noor A
    Biomed Res Int, 2014;2014:692328.
    PMID: 25025068 DOI: 10.1155/2014/692328
    A morphology study was essential to the development of the cementless femoral stem because accurate dimensions for both the periosteal and endosteal canal ensure primary fixation stability for the stem, bone interface, and prevent stress shielding at the calcar region. This paper focused on a three-dimensional femoral model for Asian patients that applied preoperative planning and femoral stem design. We measured various femoral parameters such as the femoral head offset, collodiaphyseal angle, bowing angle, anteversion, and medullary canal diameters from the osteotomy level to 150 mm below the osteotomy level to determine the position of the isthmus. Other indices and ratios for the endosteal canal, metaphyseal, and flares were computed and examined. The results showed that Asian femurs are smaller than Western femurs, except in the metaphyseal region. The canal flare index (CFI) was poorly correlated (r < 0.50) to the metaphyseal canal flare index (MCFI), but correlated well (r = 0.66) with the corticomedullary index (CMI). The diversity of the femoral size, particularly in the metaphyseal region, allows for proper femoral stem design for Asian patients, improves osseointegration, and prolongs the life of the implant.
    Matched MeSH terms: Femur/pathology; Femur Head/pathology
  2. Fulltext Molecular mechanisms of diabetic retinopathy, general preventive strategies, and novel therapeutic targets
    Safi SZ, Qvist R, Kumar S, Batumalaie K, Ismail IS
    Biomed Res Int, 2014;2014:801269.
    PMID: 25105142 DOI: 10.1155/2014/801269
    The growing number of people with diabetes worldwide suggests that diabetic retinopathy (DR) and diabetic macular edema (DME) will continue to be sight threatening factors. The pathogenesis of diabetic retinopathy is a widespread cause of visual impairment in the world and a range of hyperglycemia-linked pathways have been implicated in the initiation and progression of this condition. Despite understanding the polyol pathway flux, activation of protein kinase C (KPC) isoforms, increased hexosamine pathway flux, and increased advanced glycation end-product (AGE) formation, pathogenic mechanisms underlying diabetes induced vision loss are not fully understood. The purpose of this paper is to review molecular mechanisms that regulate cell survival and apoptosis of retinal cells and discuss new and exciting therapeutic targets with comparison to the old and inefficient preventive strategies. This review highlights the recent advancements in understanding hyperglycemia-induced biochemical and molecular alterations, systemic metabolic factors, and aberrant activation of signaling cascades that ultimately lead to activation of a number of transcription factors causing functional and structural damage to retinal cells. It also reviews the established interventions and emerging molecular targets to avert diabetic retinopathy and its associated risk factors.
    Matched MeSH terms: Blindness/pathology; Hyperglycemia/pathology
  3. Interactive knee cartilage extraction using efficient segmentation software: data from the osteoarthritis initiative
    Gan HS, Tan TS, Wong LX, Tham WK, Sayuti KA, Abdul Karim AH, et al.
    Biomed Mater Eng, 2014;24(6):3145-57.
    PMID: 25227024 DOI: 10.3233/BME-141137
    In medical image segmentation, manual segmentation is considered both labor- and time-intensive while automated segmentation often fails to segment anatomically intricate structure accordingly. Interactive segmentation can tackle shortcomings reported by previous segmentation approaches through user intervention. To better reflect user intention, development of suitable editing functions is critical. In this paper, we propose an interactive knee cartilage extraction software that covers three important features: intuitiveness, speed, and convenience. The segmentation is performed using multi-label random walks algorithm. Our segmentation software is simple to use, intuitive to normal and osteoarthritic image segmentation and efficient using only two third of manual segmentation's time. Future works will extend this software to three dimensional segmentation and quantitative analysis.
    Matched MeSH terms: Cartilage, Articular/pathology*; Osteoarthritis, Knee/pathology*
  4. Rituximab for refractory digital infarcts and ulcers in systemic sclerosis
    Khor CG, Chen XL, Lin TS, Lu CH, Hsieh SC
    Clin Rheumatol, 2014 Jul;33(7):1019-20.
    PMID: 24722688 DOI: 10.1007/s10067-014-2579-1
    Systemic sclerosis is an uncommon connective tissue disease characterised by excessive deposition of collagen and vasculopathy which affects the skin and multiple internal organs. It is associated with autoimmunity, inflammation, vasculopathy and fibrosis. Managing Raynaud's phenonemon, digital infarcts and ulcers in systemic sclerosis patients is often a challenge particularly among rheumatologists. We report a case of systemic sclerosis patient with refractory digital infarcts and ulcers responded successfully with rituximab.
    Matched MeSH terms: Fingers/pathology; Skin/pathology
  5. Fulltext CNS neurotoxicity of bacterial cellulose-poly(acrylamide-sodium acrylate) hydrogel: a future therapeutic carrier
    Pandey M, Mohd Amin MC
    CNS Neurosci Ther, 2014 Apr;20(4):377-8.
    PMID: 24588895 DOI: 10.1111/cns.12237
    Matched MeSH terms: Brain/pathology; Fibroblasts/pathology
  6. Methylation of the filaggrin gene promoter does not affect gene expression and allergy
    Tan HT, Ellis JA, Koplin JJ, Martino D, Dang TD, Suaini N, et al.
    Pediatr Allergy Immunol, 2014 Oct;25(6):608-10.
    PMID: 24912553 DOI: 10.1111/pai.12245
    Matched MeSH terms: Cheek/pathology; Skin/pathology
  7. Fulltext Estrogen receptor-negative breast ductal carcinoma: clinicopathological features and MIB-1 (Ki-67) proliferative index association
    Mdpaiman N, Md Ali SA, Mdzin R, Meor Kamal MZ, Md Amin WA, Nallusamy M, et al.
    PLoS One, 2014;9(2):e89172.
    PMID: 24586570 DOI: 10.1371/journal.pone.0089172
    Breast cancer estrogen receptor (ER) status is one of the strong additional factors in predicting response of patients towards hormonal treatment. The main aim of this study was to assess the morphological characteristics and proliferative activity using MIB-1(Ki-67) of estrogen receptor negative invasive breast ductal carcinoma (NOS type) as well as to correlate these features with clinicopathological data. We also aim to study the expression of c-erbB2 in ER negative breast tumors. High proliferative rate (MIB-1 above 20%) was observed in 63 (63.6%) of 99 ER negative tumors and that these tumors were associated with high expression of c-erbB2 (57.6%). We observed that MIB-1 is a reliable independent prognostic indicator for ER negative infiltrating ductal carcinoma in this study.
    Matched MeSH terms: Breast Neoplasms/pathology*; Carcinoma, Ductal, Breast/pathology*
  8. The influence of foot orthoses on foot mobility magnitude and arch height index in adults with flexible flat feet
    Sheykhi-Dolagh R, Saeedi H, Farahmand B, Kamyab M, Kamali M, Gholizadeh H, et al.
    Prosthet Orthot Int, 2015 Jun;39(3):190-6.
    PMID: 24604086 DOI: 10.1177/0309364614521652
    BACKGROUND: Flexible flat foot is described as a reduction in the height of the medial longitudinal arch and may occur from abnormal foot pronation. A foot orthosis is thought to modify and control excessive pronation and improve arch height.
    OBJECTIVE: To compare the immediate effect of three types of orthoses on foot mobility and the arch height index in subjects with flexible flat feet.
    STUDY DESIGN: A quasi-experimental study.
    METHOD: The dorsal arch height, midfoot width, foot mobility and arch height index were assessed in 20 participants with flexible flat feet (mean age = 23.2 ± 3 years) for three different foot orthosis conditions: soft, semi-rigid and rigid University of California Biomechanics Laboratory (UCBL).
    RESULTS: Maximum midfoot width at 90% with arch mobility in the coronal plane was shown in the semi-rigid orthosis condition. The semi-rigid orthosis resulted in the highest mean foot mobility in 90% of weight bearing, and the rigid orthosis (UCBL) had the lowest mean foot mobility. The soft orthosis resulted in foot mobility between that of the rigid and the semi-rigid orthosis. UCBL orthosis showed the highest arch height index, and the semi-rigid orthosis showed the lowest mean arch height index.
    CONCLUSION: Due to its rigid structure and long medial-lateral walls, the UCBL orthosis appears to limit foot mobility. Therefore, it is necessary to make an orthosis that facilitates foot mobility in the normal range of the foot arch. Future studies should address the dynamic mobility of the foot with using various types of foot orthoses.
    CLINICAL RELEVANCE: Although there are many studies focussed on flat foot and the use of foot orthoses, the mechanism of action is still unclear. This study explored foot mobility and the influence of foot orthoses and showed that a more rigid foot orthosis should be selected based on foot mobility.
    KEYWORDS: Foot orthosis; arch height index; foot mobility magnitude
    Matched MeSH terms: Flatfoot/pathology; Foot Joints/pathology
  9. Novel lung adenocarcinoma and nuclear factor-kappa B (NF-κB) inhibitors: synthesis and evaluation of lantadene congeners
    Suthar SK, Boon HL, Sharma M
    Eur J Med Chem, 2014 Mar 3;74:135-44.
    PMID: 24457265 DOI: 10.1016/j.ejmech.2013.12.052
    The C-3, C-17 and C-22 congeners of pentacyclic triterpenoids reduced lantadene A (3), B (4) and 22β-hydroxyoleanolic acid (5) were synthesized and were tested in vitro for their NF-κB and IKKβ inhibitory potencies and cytotoxicity against A549 lung cancer cells. The lead congeners 12 and 13 showed IC50 of 0.56 and 0.42 μmol, respectively against TNF-α induced activation of NF-κB. The congeners 12 and 13 exhibited inhibition of IKKβ in a single-digit micromolar dose and at the same time, 12 and 13 showed marked cytotoxicity against A549 lung cancer cells with IC50 of 0.12 and 0.08 μmol, respectively. The lead ester congeners were stable in the acidic pH, while hydrolyzed readily in the human blood plasma to release the active parent moieties.
    Matched MeSH terms: Adenocarcinoma/pathology*; Lung Neoplasms/pathology*
  10. Treatment outcome with brachytherapy for recurrent nasopharyngeal carcinoma
    Cheah SK, Lau FN, Yusof MM, Phua VC
    Asian Pac J Cancer Prev, 2014 Jan;14(11):6513-8.
    PMID: 24377559
    BACKGROUND: To evaluate the treatment outcome and major late complications of all patients with recurrent nasopharyngeal carcinoma (NPC) treated with intracavitary brachytherapy (ICBT) in Hospital Kuala Lumpur.

    MATERIALS AND METHODS: This retrospective study was conducted at the Department of Radiotherapy and Oncology, Hospital Kuala Lumpur, Malaysia. All patients with histologically confirmed recurrent NPC in the absence of distant metastasis treated in the period 1997-2010 were included in this study. These patients were treated with ICBT alone or in combination with external beam radiotherapy (EBRT). Treatment outcomes measured were local recurrence free survival (LRFS), disease free survival (DFS) and overall survival (OS).

    RESULTS: Thirty three patients were eligible for this study. The median age at recurrence was 56 years with a median time to initial local recurrence of 27 months. Majority of patients were staged as rT1-2 (94%) or rN0 (82%). The proportion of patients categorised as stage III-IV at first local recurrence was only 9%. Twenty one patients received a combination of ICBT and external beam radiotherapy while 12 patients were treated with ICBT alone. Median interval of recurrence post re-irradiation was 32 months (range: 4-110 months). The median LRFS, DFS and OS were 30 months, 29 months and 36 months respectively. The 5 year LRFS, DFS and OS were 44.7%, 38.8% and 28.1% respectively. The N stage at recurrence was found to be a significant prognostic factor for LRFS and DFS after multivariate analysis. Major late complications occurred in 34.9% of our patients.

    CONCLUSIONS: Our study shows ICBT was associated with a reasonable long term outcome in salvaging recurrent NPC although major complications remained a significant problem. The N stage at recurrence was a significant prognostic factor for both LRFS and DFS.

    Matched MeSH terms: Nasopharyngeal Neoplasms/pathology; Neoplasm Recurrence, Local/pathology
  11. Fulltext Serum osteocalcin is significantly related to indices of obesity and lipid profile in Malaysian men
    Chin KY, Ima-Nirwana S, Mohamed IN, Ahmad F, Ramli ES, Aminuddin A, et al.
    Int J Med Sci, 2014;11(2):151-7.
    PMID: 24465160 DOI: 10.7150/ijms.7152
    Recent studies revealed a possible reciprocal relationship between the skeletal system and obesity and lipid metabolism, mediated by osteocalcin, an osteoblast-specific protein. This study aimed to validate the relationship between serum osteocalcin and indices of obesity and lipid parameters in a group of Malaysian men.
    Matched MeSH terms: Adipose Tissue/pathology; Obesity/pathology
  12. Cytokeratin immunoreactivity in Ewing sarcoma/ primitive neuroectodermal tumour
    Elbashier SH, Nazarina AR, Looi LM
    Malays J Pathol, 2013 Dec;35(2):139-45.
    PMID: 24362477
    Ewing sarcoma (ES)/ primitive neuroectodermal tumour (PNET) is an aggressive malignant neoplasm affecting mainly children and young adults. The tumour is included with other primitive neoplasms under the category of small round cell tumour. Cytokeratin expression in ES/PNET has been described in sporadic case reports as well as a few systemic series. We studied this feature in Malaysian patients diagnosed in University Malaya Medical Centre on the basis of typical morphology and immunohistochemical assays. Immunohistochemical staining for AE1/AE3 and MNF116 were performed in 43 cases. Cytokeratin was expressed in 17 cases (39.5%) in focal, intermediate or diffuse patterns. There was no significant association between cytokeratin immunoreactivity and the following parameters: patient age, sex, skeletal and extraskeletal primary location as well as primary, metastastic or recurrent tumours or chemotherapy treatment. A significant association between cytokeratin and neuron specific enolase (NSE) expression was demonstrated. Our study supports evidence of epithelial differentiation in ES/PNET and emphasizes that the expression of cytokeratin does not exclude ES/PNET in the differential diagnosis of small round cell tumours.
    Matched MeSH terms: Sarcoma, Ewing/pathology; Neuroectodermal Tumors, Primitive/pathology
  13. BDNF rs6265 polymorphism and drug addiction: a systematic review and meta-analysis
    Haerian BS
    Pharmacogenomics, 2013 Dec;14(16):2055-65.
    PMID: 24279859 DOI: 10.2217/pgs.13.217
    A majority of studies have shown a link between the common functional rs6265 polymorphism of the BDNF gene and susceptibility to drug dependence. However, the pattern of results is inconsistent. To precisely evaluate this association, a systematic review and meta-analysis of previous case-control reports was conducted. Data from 20 studies containing 9419 participants (4665 cases and 4754 controls) conducted between 2004 and 2013 restricted to alcohol, nicotine, heroin, substance and methamphetamine dependency were meta-analyzed. Following quality control of the results, a significant association between C allele and methamphetamine dependence remained in south Asian subjects (p = 0.004). Similar results were detected in south Asian subjects for methamphetamine dependence and in Chinese subjects for heroin dependence under an autosomal codominant genotype model (TT vs CC, p = 0.005 and p = 0.0004, respectively). In conclusion, the rs6265 polymorphism may be a risk factor for methamphetamine dependence in south Asian subjects or for heroin dependence in Chinese subjects.
    Matched MeSH terms: Heroin Dependence/pathology; Substance-Related Disorders/pathology
  14. Strangulated small bowel 14 years after abdominal sacrocolpopexy
    Pue LB, Lo TS, Wu PY, Tan YL
    J Obstet Gynaecol Res, 2014 Feb;40(2):611-3.
    PMID: 24245849 DOI: 10.1111/jog.12174
    Abdominal sacrocolpopexy is a well-established procedure for the reconstruction of apical support in pelvic organ prolapse. Its long-term efficacy is well known; however, it is also associated with higher perioperative morbidity when compared with the less invasive transvaginal approach. Long-term risk of bowel-related complication from abdominal sacrocolpopexy is rare, but can be significant as it is often serious and requires major surgical intervention. Here we highlight an unusual case of strangulated small bowel (in this instance complicated with sepsis secondary to peritonitis), 14 years after an abdominal sacrocolpopexy procedure. This example amplifies the need for proper preoperative counseling; also, life-long follow-up is necessary for patients undergoing this procedure.
    Matched MeSH terms: Cecum/pathology; Ileum/pathology
  15. Retinal nerve fiber layer structure abnormalities in schizophrenia and its relationship to disease state: evidence from optical coherence tomography
    Lee WW, Tajunisah I, Sharmilla K, Peyman M, Subrayan V
    Invest Ophthalmol Vis Sci, 2013 Nov;54(12):7785-92.
    PMID: 24135757 DOI: 10.1167/iovs.13-12534
    We determined structural retinal nerve fiber layer (RNFL) changes in schizophrenia patients and established if the structural changes were related to the duration of the illness using spectral-domain optical coherence tomography (SD-OCT).
    Matched MeSH terms: Nerve Fibers/pathology*; Retinal Diseases/physiopathology; Retinal Ganglion Cells/pathology*
  16. Functional thoracic hyperkyphosis model for chronic subacromial impingement syndrome: an insight on evidence based "treat the cause" concept--a case study and literature review
    Nagarajan M, Vijayakumar P
    J Back Musculoskelet Rehabil, 2013;26(3):227-42.
    PMID: 23893137 DOI: 10.3233/BMR-130373
    Recent evidences suggest functional thoracic hyperkyphosis (FTH) could be a different approach in the management of subacromial impingement syndrome (SIS). This case study aims firstly with the development of evidence informed FTH model for SIS. Secondly this study aimed to develop well defined multimodal physical therapy intervention for FTH and its related mechanical consequences in elderly patient with chronic SIS. As a result, Level IV positive evidence was found in both the short and long-term pain and disability of chronic SIS, using FTH model with 26 months of follow-up.
    Matched MeSH terms: Shoulder Joint/pathology; Shoulder Impingement Syndrome/pathology
  17. Neurosyphilis and psychosis
    Wahab S, Md Rani SA, Sharis Othman S
    Asia Pac Psychiatry, 2013 Apr;5 Suppl 1:90-4.
    PMID: 23857843 DOI: 10.1111/appy.12050
    Neurosyphilis may presents with a range of psychiatric symptoms. This report illustrates a case of neurosyphilis in a man who presented with psychosis and cognitive dysfunction. Clinical findings and investigations done in the present case showed positive results for syphilis. Reduction of symptoms was noted after treatment with antibiotic. This case further highlights the importance of having high index of suspicion for neurosyphilis in patients presenting with psychiatric symptoms.
    Matched MeSH terms: Brain/pathology; Neurosyphilis/pathology
  18. Global search for right cell type as a treatment modality for cardiovascular disease
    Musa S, Xin LZ, Govindasamy V, Fuen FW, Kasim NH
    Expert Opin Biol Ther, 2014 Jan;14(1):63-73.
    PMID: 24191782 DOI: 10.1517/14712598.2014.858694
    Acute myocardial infarction is the primary cause of heart disease-related death in the world. Reperfusion therapy is currently the backbone of treatment for acute myocardial infarction albeit with many limitations. With the emergence of stem cells as potential therapeutic agents, attempts in using them to enhance cardiac function have increased exponentially. However, it has its own disadvantages, and we postulate that the primary drawback is choosing the right cell type and solving this may significantly contribute to ambitious goal of using stem cells in the regeneration medicine.
    Matched MeSH terms: Myocardial Infarction/pathology; Myocardial Infarction/physiopathology; Myocytes, Cardiac/pathology
  19. The influence of fenofibrate on lipid profile, endothelial dysfunction, and inflammatory markers in type 2 diabetes mellitus patients with typical and mixed dyslipidemia
    Ghani RA, Bin Yaakob I, Wahab NA, Zainudin S, Mustafa N, Sukor N, et al.
    J Clin Lipidol, 2013 Sep-Oct;7(5):446-53.
    PMID: 24079286 DOI: 10.1016/j.jacl.2013.04.004
    BACKGROUND: Type 2 diabetes is associated with early development of endothelial dysfunction. Patients present with typical dyslipidemia (predominantly high levels of triglycerides [TG] and low levels of high-density lipoprotein cholesterol [HDL-C]) or mixed hypercholesterolemia (high levels of low-density lipoprotein cholesterol [LDL-C] and TG with low HDL-C). Normal levels include LDL-C < 100 mg/dL, TG < 135 mg/dL, and HDL-C > 40 mg/dL for men and >50 mg/dL for women.
    OBJECTIVE: To determine the effects of 8 weeks' administration of fenofibrate on inflammatory markers, metabolic parameters, and endothelial dysfunction.
    METHODS: We administered micronized fenofibrate (Laboratories Fourneir S.A Dijon, France) daily for 8 weeks to 40 dyslipidemic, type 2 diabetes patients with equal numbers in each arm of the typical or mixed dyslipidemia groups. Noninvasive endothelial function assessments were performed and serum inflammatory markers obtained before and after treatment.
    RESULTS: The typical group demonstrated significantly greater TG reduction and HDL-C increment, ie, 56% vs, 21.3% (P < .005) and 21% vs. 7.6% (P = .001), respectively, compared with the mixed group. There was greater LDL-C reduction within the mixed group compared with the typical group 21.0% vs. 2.2% (P < .05). Endothelial dysfunction was present in both groups at baseline. After treatment, the typical group demonstrated significant improvement in resting brachial diameter (3.9 mm [interquartile range {IQR} 3.3-4.7] to 4.2 mm [IQR 3.4-4.8], P = .001) compared with no change within the mixed group (3.6 mm [IQR 3.1-5.4] to 3.7 mm [IQR 3.1-5.3], P = .26). Flow-mediated diameter improved significantly in both groups. The mixed group had significantly greater levels of hs-CRP at baseline but no changes throughout the study. The mixed group demonstrated an increase in vascular adhesion molecule-1 from 706 ng/mL (IQR 566-1195) to 845 ng/mL (637-1653; P = .01), a reduction of tumor necrosis factor-α from 7.0 pg/mL (IQR 1.0-43.5) to 2.5 pg/mL (IQR 1.5-13.5; P = .04) throughout the study.
    CONCLUSIONS: We effectively compared 8 weeks of fenofibrate therapy in type 2 diabetics with contrasting lipid abnormalities. The typical dyslipidemia group showed significantly greater lipid improvements compared with the mixed dyslipidemia group. Both groups had improvements in endothelial functions that were independent of the lipid levels. We concluded that fibrate therapy in type 2 diabetics is beneficial, especially those with typical dyslipidemia and extends beyond its lipid lowering properties.
    KEYWORDS: Endothelial dysfunction; Fenofibrate; High-density lipoprotein cholesterol; Low density lipoprotein; Noninvasive endothelial function assessments; Triglyceride; Vascular cell adhesion molecule-1; hsCRP
    Matched MeSH terms: Endothelium/pathology; Dyslipidemias/pathology*
  20. Effect of intra-cisternal application of kainic acid on the spinal cord and locomotor activity in rats
    Mitra NK, Goh TE, Bala Krishnan T, Nadarajah VD, Vasavaraj AK, Soga T
    Int J Clin Exp Pathol, 2013;6(8):1505-15.
    PMID: 23923068
    Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease of idiopathic etiology. Glutamate excitotoxicity is one of the proposed hypotheses causing progressive death of motor neurons. We aimed to develop an experimental animal model of this disease to enhance the knowledge of pathophysiological mechanism of ALS. Male Wistar rats were infused with Kainic acid (KA) intra-cisternally for 5 days at the dosage of 50 fmol/day and 150 fmol/day. Locomotor activity, sensory function and histological changes in cervical and lumbar sections of spinal cord were evaluated. Glial Fibrillary Acidic Protein (GFAP) and Neurofilament Protein (NFP) were used as immunohistochemical marker for reactive astrogliosis and neuronal damage respectively. Specific Superoxide Dismutase (SOD) activity of spinal cord was estimated. The locomotor activity in the parameter of observed mean action time remained reduced on 14(th) day after administration of KA. Spinal motor neurons under Nissl stain showed pyknosis of nucleus and vacuolation of neuropil. GFAP expression increased significantly in the lumbar section of the spinal cord with high dose of KA treatment (p<0.05). NFP was expressed in axonal fibres around the neurons in KA-treated rats. A significant increase in specific SOD activity in both cervical and lumbar sections of the spinal cord was found with low dose of KA treatment (p<0.05). This study concludes that spinal cord damage with some features similar to ALS can be produced by low dose intra-cisternal administration of KA.
    Matched MeSH terms: Neurons/pathology; Spinal Cord/pathology
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