Medicine
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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty
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Item Variants of acan gene associate with severity of lumbar disc degeneration(Sri Lanka Medical Association, 2016) Perera, G.L.R.S.; Wijayaratne, L.S.; Senarath, U.; Dissanayake, P.H.; Karunanayake, A.L.; Dissanayake, V.H.W.INTRODUCTION AND OBJECTIVES: Structural integrity of aggrecan (coded by ACAN gene) plays a major role in lumbar disc degeneration (LDD). Single nucleotide polymorphisms (SNPs) of ACAN gene have been implicated in LDD. The study aimed to determine the associations between SNPs of ACAN gene and the severity of disc space narrowing (DSN) and osteophytes (OS) of lumbar spine in patients with chronic mechanical low back pain (CMLBP). METHOD: A descriptive cross-sectional study was carried out on 120 patients with CMLBP. Lateral lumbar X-rays were assessed for severity of DSN and OS using a semiquantitative scores (grade 0-3). Twenty-seven exonic SNPs of the ACAN gene were genotyped on a Sequenom mass array iPLEX platform. Multiple linear regression analysis was carried out adjusting for age and body mass index. RESULTS: Mean age was 51.46 ± 10.43 years. 82 (68.3%) were females. 30 (25%) were obese. 31 (25.8%) and 47 (39.2%) had grade 1 DSN and AOS respectively, while 42 (35%) and 13 (10.8%) had grade ≥ 2 DSN and AOS, respectively. “A” allele of rs2882676 (regression coefficient (β) = -0.25, p<0.03), “A” allele of rs1042630 (β = -0.28, p<0.01) and “T” allele of rs1042631 (β = -0.28, p<0.02) were negatively associated with the severity of DSN. “T” allele of rs16942341 (β = 0.4, p<0.02) and “G” allele of rs28407189 (β = 0.4, p<0.02) were positively associated with the severity of AOS. CONCLUSION: SNPs of ACAN gene are associated with severity of degenerative changes of the lumbar spine.Item Variants of ACAN are associated with severity of lumbar disc herniation in patients with chronic low back pain(Public Library of Science, 2017) Perera, R.S.; Dissanayake, P.H.; Senarath, U.; Wijayaratne, L.S.; Karunanayake, A.L.; Dissanayake, V.H.W.INTRODUCTION: Disc herniation is a complex spinal disorder associated with disability and high healthcare cost. Lumbar disc herniation is strongly associated with disc degeneration. Candidate genes of the aggrecan metabolic pathway may associate with the severity of lumbar disc herniation. OBJECTIVES: This study evaluated the association of single nucleotide variants (SNVs) of the candidate genes of the aggrecan metabolic pathway with the severity of lumbar disc herniation in patients with chronic mechanical low back pain. In addition, we assessed the in-silico functional analysis of the significant SNVs and association of their haplotypes with the severity of lumbar disc herniation. METHODS: A descriptive cross sectional study was carried out on 106 patients. Severity of disc herniation and disc degeneration were assessed on T2-weighted mid sagittal lumbar MRI scan. Sixty two exonic SNVs of ten candidate genes of aggrecan metabolic pathway (ACAN, IL1A, IL1B, IL6, MMP3, ADAMTS4, ADAMTS5, TIMP1, TIMP2 and TIMP3) were genotyped on a Sequenom MassARRAY iPLEX platform. Multivariable linear regression analysis was carried out using PLINK 1.9 software adjusting for age, gender, body mass index and severity of disc degeneration. Four online bioinformatics tools (Provean, SIFT, PolyPhen and Mutation Taster) were used for in-silico functional analysis. RESULTS: Mean age was 52.42 ± 9.42 years and 69.8% were females. The mean severity of disc herniation was 2.81 ± 1.98. The rs2272023, rs35430524, rs2882676, rs2351491, rs938609, rs3825994, rs1042630, rs698621 and rs3817428 variants and their haplotypes of ACAN were associated with the severity of lumbar disc herniation. However, only the rs35430524, rs938609 and rs3817428 variants of ACAN were detected as pathogenic by in-silico functional analysis. CONCLUSIONS: SNVs of ACAN and their haplotypes are associated with the severity of lumbar disc herniation. Functional genetic studies are necessary to identify the role of these significant SNVs in the pathogenesis of disc herniation.Item Associations between disc space narrowing, anterior osteophytes and disability in chronic mechanical low back pain: a cross sectional study(BioMed Central, 2017) Perera, R.S.; Dissanayake, P.H.; Senarath, U.; Wijayaratne, L.S.; Karunanayake, A.L.; Dissanayake, V.H.W.BACKGROUND: Radiographic features of lumbar disc degeneration (LDD) are common findings in patients with chronic mechanical low back pain; however, its role in disability and intensity of pain is debatable. This study aims to investigate the associations of the x-ray features of LDD and lumbar spondylolisthesis with severity of disability and intensity of pain. METHODS: A cross-sectional study was conducted on 439 patients with chronic mechanical low back pain who attended the rheumatology clinic, National Hospital of Sri Lanka, Colombo, from May 2012 to May 2014. Severity of disability was measured using Modified Oswestry Disability Index and intensity of pain was assessed using numeric rating scale (0-100). X-ray features of LDD (disc space narrowing, anterior osteophytes and overall LDD) and spondylolisthesis were assessed in lateral recumbent lumbar x-rays (L1/L2 to L5/S1) and graded by a consultant radiologist blinded to clinical data. Generalised linear model with linear response was used to assess the associations of x-ray features of LDD with severity of disability and intensity of pain adjusting for age, gender, body mass index and pain radiating into legs. RESULTS: Mean age was 48.99 ± 11.21 and 323 (73.58%) were females. 87 (19.82%) were obese. Mean severity of disability was 30.95 ± 13.67 and mean intensity of pain was 45.50 ± 20.37. 69 (15.72%), 26 (5.92%) and 85 (19.36%) patients had grade 2 disc space narrowing, anterior osteophytes and overall LDD, respectively. 51 (11.62%) patients had lumbar spondylolisthesis. Grade of disc space narrowing and overall LDD were not associated with severity of disability or intensity of pain. The presence of lumbar spondylolisthesis was associated with severity of disability. Female gender and pain radiating into legs were associated with severity of disability and intensity of pain. Advancing age was associated with x-ray features of LDD and lumbar spondylolisthesis. CONCLUSIONS: Lumbar spondylolisthesis is associated with severity of disability in patients with chronic mechanical low back pain. Associations of x-ray features of LDD with severity of disability and intensity of pain are inconclusive. Female gender and pain radiating into legs are significant confounders.Item Chronic low back pain and its association with lumbar vertebrae and intervertebral disc changes in adults. A case control study(Wiley, 2018) Karunanayake, A.L.; Pathmeswaran, A.; Wijayaratne, L.S.AIM: This study was done to determine the association between chronic low back pain and vertebral fractures, intervertebral disc space (IDS) narrowing, vertebral osteophytes and spondylolisthesis among adults. METHOD: This case control study was done in Sri Lanka. Cases were patients with low back pain and controls were without low back pain. Postero-anterior and lateral radiographs of lumbar sacral spine of both groups were studied. To detect vertebral fractures in fourth and fifth lumbar vertebrae, anterior and posterior heights of vertebrae were measured using a Vernier caliper and antero-posterior ratio (A/P) was calculated. Having an A/P ratio value of < 0.89 was considered as a vertebral fracture. Presence of disc space narrowing, vertebral osteophytes and spondylolisthesis was assessed by two radiologists working independently. Bivariate and logistic regression analysis was done to find associations. RESULTS: There were 140 cases and 140 controls. Mean (SD) age for cases was 51.6 (17) years. Mean (SD) age for controls was 50 (15) years. Females made up 62% of cases and controls. Fifth lumbar vertebral fracture (odds ratio [OR] = 10.2; P = 0.001), fourth lumbar vertebral fracture (OR = 2.5; P = 0.017) and IDS narrowing (OR = 4.15, P = 0.009) had a significant association with low back pain and vertebral osteophytes and spondylolisthesis did not have a significant association with low back pain. CONCLUSION: Only vertebral fractures and IDS narrowing had a significant association with chronic low back pain.Item Single nucleotide variants of candidate genes in aggrecan metabolic pathway are associated with lumbar disc degeneration and modic changes(Public Library of Science, 2017) Perera, R.S.; Dissanayake, P.H.; Senarath, U.; Wijayaratne, L.S.; Karunanayake, A.L.; Dissanayake, V.H.W.INTRODUCTION: Lumbar disc degeneration (LDD) is genetically determined and severity of LDD is associated with Modic changes. Aggrecan is a major proteoglycan in the intervertebral disc and end plate. Progressive reduction of aggrecan is a main feature of LDD and Modic changes. OBJECTIVES: The study investigated the associations of single nucleotide variants (SNVs) of candidate genes in the aggrecan metabolic pathway with the severity of LDD and Modic changes. In-silico functional analysis of significant SNVs was also assessed. METHODS: A descriptive cross sectional study was carried out on 106 patients with chronic mechanical low back pain. T1, T2 sagittal lumbar MRI scans were used to assess the severity of LDD and Modic changes. 62 SNVs in ten candidate genes (ACAN, IL1A, IL1B, IL6, MMP3, ADAMTS4, ADAMTS5, TIMP1, TIMP2 and TIMP3) were genotyped on Sequenom MassARRAY iPLEX platform. Multiple linear regression analysis was carried out using PLINK 1.9 in accordance with additive genetic model. In-silico functional analysis was carried out using Provean, SIFT, PolyPhen and Mutation Taster. RESULTS: Mean age was 52.42±9.42 years. 74 (69.8%) were females. The rs2856836, rs1304037, rs17561 and rs1800587 variants of the IL1A gene were associated with the severity of LDD and Modic changes. The rs41270041 variant of the ADAMTS4 gene and the rs226794 variant of the ADAMTS5 gene were associated with severity of LDD while the rs34884997 variant of the ADAMTS4 gene, the rs55933916 variant of the ADAMTS5 gene and the rs9862 variant of the TIMP3 gene were associated with severity of Modic changes. The rs17561 variant of the IL1A gene was predicted as pathogenic by the PolyPhen prediction tool. CONCLUSIONS: SNVs of candidate genes in ACAN metabolic pathway are associated with severity of LDD and Modic changes in patients with chronic mechanical low back pain. Predictions of in-silico functional analysis of significant SNVs are inconsistent.Item Gross anatomical variations of lumbar vasculature among Sri Lankan adults: a cadaveric study(Sri Lanka Medical Association, 2003) Karunanayake, A.L.; Jayasinghe, J.A.P.; Wijayaratne, L.S.; Pathmeswaran, A.BACKGROUND: Lumbar arteries supply intervertebral discs, vertebrae, muscles and ligaments in the lumbar region. Lumbar arteries can get damaged during urological and vascular surgery. According to textbooks of anatomy there are four pairs of lumbar arteries arising as individual stems from abdominal aorta and they travel posterior to crura of the diaphragm. There are no published studies in Sri Lanka either confirming this or describing the variations of lumbar arteries. OBJECTIVE: To describe the anatomy of lumbar arteries with regard to their numbers, origin and pathway. MATERIALS AND METHODS: This descriptive study was done on cadavers in anatomy departments of Kelaniya, Colombo and Sri Jayawardenepura Universities. Lumbar arteries were cleared from the origin of the abdominal aorta up to the point of passing deep to the Psoas major muscle. Their origin, number and pathway were noted. RESULTS: Dissected 109 cadavers. Ages ranged 43 -90 years. Mean age 70 years (SD 13.6). Males constituted 57% of the sample. The number of lumbar arteries varied from 3-5 pairs. In 12% of cadavers lumbar arteries originated as a common stem from the aorta and divided into two. These arteries traveled anterior to crura of the diaphragm in 17% of cadavers. CONCLUSIONS: There were variations with regard to the number, origin from abdominal aorta and pathway of lumbar arteries from what is described in textbooks. These findings will be useful for surgeons performing retroperitoneal surgery.Item Radiological features of chronic low back pain (LBP) in adult Sri Lankans; A case control study(Sri Lanka Medical Association, 2003) Karunanayake, A.L.; Fonseka, M.M.D.; Pathmeswaran, A.; Wijayaratne, L.S.BACKGROUND: Chronic LBP affects 30% of adult Sri Lankans. The presence of vertebral osteophytes, spondylolisthesis and disc space narrowing are thought to be important contributing factors of LBP. No studies have been done in Sri Lanka, investigating the importance of these in LBP. Objective: To determine the association between chronic LBP and vertebral osteophytes, spondylolisthesis and disc space narrowing. MATERIALS AND METHODS: A case control study was done in two hospitals in Ragama. Cases and controls were selected from medical, surgical and orthopaedic wards and clinics. They were matched for age and sex. Subjects who were 18 years and above with chronic LBP (more than three months) were selected as cases. Patients who were 18 years and above without LBP were selected as controls. They had symptoms such as abdominal pain and dysuria requiring radiography. In both groups postero-anterior and lateral radiographic appearances of the lumbar spine were studied. RESULTS: There were 130 cases and 130 controls. Age range was 18 -82 years. Mean age of patients was 49.3 years (SD 15). Mean age of controls was 51.4 years (SD 17). Females constituted 62% of cases and controls. Vertebral osteophytes were present in 72% of cases and 64% of controls (P = 0.184). Spondylolisthesis was present in 8% of cases and 7% of controls (P = 0.959). Disc space narrowing was present in 15% of cases and 2% of controls (OR = 7.8, P =0.0004). CONCLUSIONS: Disc space narrowing was significantly higher in patients with LBP.Item Effect of atherosclerosis on lumbar intervertebral disc cells in a sample of Sri Lankan population: a postmortem study(Sri Lanka Medical Association, 2004) Karunanayake, A.L.; Pathmeswaran, A.; Wijayaratne, L.S.; Fonseka, M.M.D.BACKGROUND: Disc degeneration is an important cause of low backache. The cartilage cells of the disc are important to maintain the structure and function of intervertebral discs. Lumbar arteries provide blood supply to lumbar discs. OBJECTIVE: To describe the association between cell density of fourth lumbar intervertebral disc and atherosclerotic changes of fourth lumbar artery openings. METHODS: Descriptive study was done on 4th lumbar intervertebral disc and 4lh lumbar arteries of postmortem specimens. H&E sections were prepared on the annulus fibrosus of lumbar discs. Atherosclerotic changes of lumbar artery openings were studied. By using a graticule number of cells per 4mm" were counted in each disc specimen in ten low power fields and mean cell density was calculated. Cell density of less than three was categorized as low cell density. Atherosclerotic changes of lumbar arteries were graded into three groups according to severity. Grade 1 was the least severe and grade 3 was the most severe. The chi-square for trend was used to find the association between the atherosclerotic changes of lumbar arteries and the cell density. RESULTS: 31 postmortem specimens. Age range 21 - 96 years. Median age 43 years. There was a significant association (P = 0.005) between atherosclerotic changes of lumbar arteries and low cell density. OR for gradcl, grade 2 and grade 3 was I, 4.5 and 18 respectively. CONCLUSIONS: Atherosclerotic changes of lumbar arteries had a significant negative association with the cell density.Item Association between pain and disability in patients with chronic mechanical low back pain(Sri Lanka Medical Association, 2015) Perera, G.L.R.S.; Wijayaratne, L.S.; Senarath, U.; Dissanayake, P.H.; Karunanayake, A.L.; Dissanayake, V.H.W.INTRODUCTION AND OBJECTIVES: Low back pain is the leading cause of years lived with disability in developed countries as well as in South Asian countries. The aim of this study is to evaluate the association between the intensity of pain and disability in patients with chronic mechanical low back pain (CMLBP) who attended the rheumatology clinic, National Hospital of Sri Lanka (NHSL). METHOD: This is a descriptive study on 675 patients with CMLBP who attended the rheumatology clinic, NHSL, from May 2012 to May 2014, recruited according to inclusion and exclusion criteria. Intensity of pain was measured using the 101-point numerical pain rating scale (NRS) and the disability was measured using the modified Oswestry Disability Index (MODI). A multiple linear regression model adjusted for age, gender, level of education, duration and frequency of pain and duration of treatment was used to assess the association between the intensity of pain and disability. RESULTS: Majority (482, 71.4%) were females. Mean age was 49.19 ± 11.75 years. Mean score for NRS was 46.79 ± 20.38 and for MODI was 31.77 ± 14.16, while 84.3% had daily pain. Intensity of pain was positively associated with the disability (p<0.01) and the standardized regression coefficient was +0.627 after adjusting for confounders. Frequency of pain, female gender and aging were positively associated with disability (p<0.05) while level of education, and durations of pain and treatment did not reach significant level. Conclusion: Intensity of pain explains 63% of the disability associated with CMLBP. Frequency of pain, female gender and age were also associated with disability.Item Association between the intima media thickness of lumbar arteries and the cell density of lumbar intervertebral discs: a postmortem study among Sri Lankan adults(Sri Lanka Medical Association, 2005) Karunanayake, A.L.; Pathmeswaran, A.; Fonseka, M.M.D.; Wijayaratne, L.S.BACKGROUND: Disc degeneration is an important cause of low backache. Cartilage cells help to maintain the structure of the disc. The lumbar arteries provide blood supply to the lumbar discs. The tunica media affects the mechanical properties of the vessel wall and thereby control the blood supply to the tissues. OBJECTIVES: To describe the association between the intima media thickness (expressed as a percentage of total thickness) of 4th lumbar artery and the mean cell density of the 4th lumbar disc. METHODS: Descriptive cross sectional study was done on 4th lumbar discs and 4th lumbar arteries of postmortem specimens. H&E sections were prepared on the annulus fibrosus of lumbar discs and lumbar arteries. By using a graticule number of cells per 4mm2 were counted in each disc specimen in ten low power fields and the mean cell density was calculated. With a graticule measurement of intima media thickness (IMT) and total thickness of lumbar arteries were taken on each artery specimen in ten low power fields. Mean of IMT expressed as a percentage of TT was calculated. Correlation coefficient was calculated to find out the association between the IMT and the mean cell density. RESULTS: Postmortem specimens of 31 subjects aged between 21-96 years (mean age 46 years. SD 19 years) were examined. 24 were males. There was a significant association between the IMT and the cell density (r = 0-37, P< 0.05). CONCLUSIONS: IMT of lumbar arteries had a significant positive association with the cell density.