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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty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 RB1 screening of retinoblastoma patients in Sri Lanka using targeted next generation sequencing (NGS) and gene ratio analysis copy enumeration PCR (GRACE-PCR)(BioMed Central, 2023) Kugalingam, N.; de Silva, D.; Abeysekera, H.; Nanayakkara, S.; Tirimanne, S.; Ranaweera, D.; Suravajhala, P.; Chandrasekharan, V.BACKGROUND: Retinoblastoma (RB) a tumour affecting those under 5 years, has a prevalence of 1 in 20,000, with around twenty new diagnoses per year in Sri Lanka. Unilateral and bilateral RB presents around 24 and 15 months respectively. Approximately 10% are familial. Systematic genetic testing for germline pathogenic variants of RB1, the only gene associated with an inherited risk of RB, is unavailable in Sri Lanka. Genetic testing optimizes management of affected children and at-risk siblings. This study aimed to develop accessible genetic testing to identify children with a germline pathogenic variant of RB1 in Sri Lanka. METHODS: Targeted next generation sequencing (NGS) for detecting pathogenic sequence variants and Gene Ratio Analysis Copy Enumeration PCR (GRACE-PCR) for detecting RB1 copy number variations (CNVs) were performed for 49 consecutive RB patients treated between 2016 and 2020 at the designated RB care unit, Lady Ridgway hospital, Colombo. Patients (bilateral RB (n = 18; 37%), unilateral n = 31) were recruited following ethical clearance and informed consent. RESULTS: There were 26 (53%) females. Mean age at diagnosis was 18 months. Thirty-five patients (71%) had undergone enucleation. Germline pathogenic variants of RB1 identified in 22/49 (45%) patients including 18 (37%; 12 bilateral and 6 unilateral) detected by targeted NGS (2 missense, 7 stop gained, 1 splice donor, 8 frameshift variants). Six were previously undescribed, likely pathogenic frameshift variants. Four bilateral RB patients had GRACE-PCR detected CNVs including one whole RB1, two intragenic deletions (exon 12/13; exon 11 and 23) and a partial duplication of exon 27. The only familial case (affected mother and child) shared the duplication. Only 2 of 4 CNVs and 10 of 18 pathogenic variants were confirmed by whole exome sequencing and Sanger sequencing respectively, due to funding limitations. CONCLUSIONS: The study identified pathogenic or likely pathogenic germline RB1 sequence variants and copy number variants in 16/18 (89%) bilateral and 6/31(19%) unilateral cases, which is comparable to worldwide data (10-15% unilateral, 80-85% bilateral). Targeted NGS combined with GRACE-PCR significantly reduce the cost of RB1 testing in Sri Lanka, and may widen access for genetic diagnosis of RB patients in other low and middle income countries.Item Thyroid gland and male reproductive anomalies among fuel handlers in Gampaha district, Sri Lanka(Endocrine Society, 2021) Kottahachchi, D.C.; Warnakularuriya, T.; de Silva, D.; Madagoda, K.; Wadasinghe, D.; Dayanath, B.K.T.P.I.; Siyambalapitiya, S.; Devanarayana, N.Introduction:Fuel handlers at petrol stations are continuously exposed to organic solvents from fuel and vehicle emissions. Endocrine disrupting chemicals (EDC) are present in fuel, which are harmful to endocrine organs. Thyroiditis and hypogonadism are reported among fuel handlers. Thyroid gland and male reproductive function anomalies were investigated among fuel handlers in the Gampaha district of Sri Lanka. Method: 43 were recruited from 6 fuel stations in the Gampaha district for the study and 28 age matched male workers who were not exposed to fuel in an occupational setting were recruited as controls. Thyroid gland was examined clinically and TSH, free T4, FSH, LH and Testosterone were done on all the participants. TPO antibody and a thyroid scan was done on the fuel handlers. Results: Median (IQR) age was 38 years (27-46 years). The mean TSH value was 1.62 IU/mL (1.15-2.35) vs 1.33 IU/mL (0.83-1.79) respectively in study and control populations with significantly higher levels in the study population (p=0.023). The median (IQR) TSH value above the reference range was identified in 7% of fuel handlers and all controls were within the normal range, while 16.9% of fuel handlers had a derangement in the TPO levels. On examination, only one control had a small goiter but his T4 and TSH levels were normal. On ultrasound thyroid scans, benign nodules were seen in 2 fuel handlers. TPO levels did not correlate with the TSH levels among the fuel handlers (r=-0.078, p=0.652). Inability to sustain an erection was reported by 35.5% fuel handlers which was significantly higher than controls who reported 5.6% (p=0.019). Premature ejaculation was reported by 27.9% of fuel handlers which was significantly higher than controls (p=0.023). The testosterone levels were significantly higher among fuel handlers compared to controls (p=0.048). The FSH and LH levels positively correlated with each other as expected in each subgroup and the total population (p<0.005). The TSH levels significantly negatively correlated with the testosterone levels among the fuel handlers. (r=- 0.338, p=.0.023). When the fuel handlers with premature ejaculation was considered the FSH, LH, Testosterone levels were not significantly different between the two groups, however the duration of employment was significantly longer among those reporting premature ejaculation. (p=0.024). Conclusion: There are thyroid and reproductive abnormalities among those exposed to fuel in an occupational setting. Disturbances to sexual functions may also be related to alteration of autonomic functions. Limiting exposure to fuel vapor will eliminate these detrimental effects and we propose self-service fuel pumps to be the best alternative to avoid occupational health hazards among fuel handlers.Item Arterial tortuosity syndrome: A rare inherited form of connective tissue disorder with SLR2A10 gene mutation(Sri Lanka College of Paediatricians, 2022) Wijesinghe, S.; de Silva, D.; Samarasinghe, D.; Irugalbandara, S.No abstract availableItem Identification of staphylococci contaminating clinical white coats of 4th year medical students(Faculty of Medicine, University of Kelaniya, Sri Lanka, 2021) Daraniyagala, H.U.; Dahanayake, O.S.; Dasanayake, A.P.; Dayarathna, M.P.; Dayarathna, S.N.; Dayasiri, K.G.; de Silva, D.N.; de Silva, S.A.; de Silva, N.U.; de Silva, D.; de Zoysa, D.S .; Vidanapathirana, G.; Dissanayake, R.U.; Ekanayake, A.; Liyanapathirana, V.Introduction: Infections caused by-resistant bacteria (ARB) have become a major global issue. Medical students’ clinical white coats can harbor these organisms and function as a possible reservoir for ARB transmission during their clinical training. More common species that contaminate clinical white coats include Staphylococcus aureus and its antibiotic-resistant variation, Methicillin-Resistant Staphylococcus aureus (MRSA). Objectives: To determine the prevalence of S. aureus and MRSA contamination of clinical white coats worn by medical students. Methods: A cross-sectional study was done with the participation of 4th-year medical students of the Faculty of Medicine, University of Peradeniya. Swabs were taken from the pockets and sleeves of the clinical white coats, and S. aureus was identified using routine microbiological methods. Disc diffusion-based cefoxitin sensitivity test was used to identify MRSA isolates among the S. aureus. Results: S. aureus has contaminated 53 (35.1%) of the 151 white coats of participants. MRSA was found in 20 (30.30%) of the isolates, accounting for 15 (9.9%) of the total participants. Factors analysed, including sex, type of clinical appointment and frequency of washing white coats were not found to be significantly associated with contamination by either of bacteria. Conclusions: Clinical white coats worn by medical students were found to be heavily contaminated with S. aureus and MRSA. As a result, these coats can be regarded as a potential mode of infection transmission between individuals. Therefore, steps should be taken to rectify the proper use and cleaning of medical students’ white clinical coats.Item Anxiety and Depression among the patients with Dysphagia following Oral Maxillofacial and Neck surgeries in four selected hospitals in Western Province, Sri Lanka.(Faculty of Medicine, University of Kelaniya, Sri Lanka, 2021) Fernando, K.; Fernando, R.; de Silva, D.Introduction: Undiagnosed anxiety and depression are obstacles to effective management of post-operative dysphagia. In Sri Lanka, the prevalence of anxiety and depression among patients with postoperative dysphagia is not known. Objectives: This study aimed at determining the severity and the stage of dysphagia, presence of anxiety and depression, and to identify the association between the severity and the stage of dysphagia with anxiety and depression following Neck, Oral & Maxillo-Facial (OMF) Surgeries. Methods: A cross-sectional study was conducted among 97 participants, with post¬operative dysphagia following OMF and Neck surgeries at four selected hospitals. Oral-motor and cranial nerve examination, the 3 ml water test, Cervical auscultation, Dysphagia Severity Rating Scale and Hospital Anxiety and Depression Scale were used for data collection. Results: Among the participants 51% presented with pharyngeal phase dysphagia and severe dysphagia. Prevalence of depression was 51% and anxiety was 38%, while 35% and 45% were at the borderline range respectively. With the increasement of dysphagia severity, high levels of anxiety and depression were noted. There was a statistically significant association between the severity of anxiety with severity of dysphagia (p< 0.05). Conclusion: Psychological burden is high among the participants with dysphagia following OMF and neck surgeries. Holistic management of dysphagia following OMF and neck surgeries, should include an assessment of the mental state of these patients and the treatment of anxiety and depression if required.Item Nail-patella syndrome: Clinical importance of diagnosis(Sri Lanka College of Paediatricians, 2021) Kaleel, F.; Gunasekera, R.; de Silva, D.No abstract availableItem Lung function of fuel handlers exposed to volatile organic compounds(Journal of the Ceylon College of Physicians, 2020) Wadasinghe, D.; Warnakulasuriya, T.; Medagoda, K.; Kottahachchi, D.; Luke, D.; Ariyawansa, J.; Rathnayake, P.; Dissanayake, T.; de Silva, D.; Amarasiri, L.; Devanarayana, N.M.; Scheepers, P.INTRODUCTION AND OBJECTIVES: The respiratory system is a target for effects from air pollutants, including vehicle emissions composed of volatile organic compounds (VOC), particulate matter and other noxious gasses. Our objective was to study the association between selected VOCs and lung function in a cohort of fuel handlers. METHOD: Forty-four fuel handlers (men) from the Gampaha district of Sri Lanka aged 19-65 years were selected using consecutive sampling with a group of 38 males matched by age, without occupational exposure to fuel recruited as controls. Spirometry was performed using a Vitalograph Alpha Touch spirometer, according to ATS guidelines. Pre and post shift VOC levels were measured in end exhaled air samples. RESULTS: The spirometry parameters were not significantly different between the two groups but obstructive (47.72% vs.34.21%) and restrictive ventilatory patterns (31.81% vs. 21.05%) were higher among the fuel handlers. FVC and FEV1 negatively correlated with age (r=-0.672, p<0.001 and r=-6.888, p<0.001 respectively) and number of days of exposure (r=-0.329, p=0.033 and r=-0.306, p=0.049 respectively). Among the fuel handler's, benzene exposure negatively correlated with FVC (r=-0.552, p=0.012) and FEV1 (r=-0.476, p=0.034) and toluene exposure negatively correlated with PEF (r=-0.488, p=0.034). Although levels of all VOCs measured were significantly low among the controls, toluene exposure levels negatively correlated with all spirometry parameters (p<0.05). CONCLUSIONS: A decline in lung function is seen with more days of exposure as a fuel handler. The different vVOCs· affect the volume parameters and flow parameters uniquely and even non-occupational exposure causes an alteration of spirometry parameters among adult males.Item Autonomic functions among fuel handlers in the Gampaha District(Journal of the Ceylon College of Physicians, 2020) Medagoda, K.; Warnakulasuriya, T.; Kottahachchi, D.; Luke, D.; Wadasinghe, D.; Ariyawansha, J.; Rathnayaka, P.; Dissanayake, T.; de Silva, D.; Devanarayana, N.M.INTRODUCTION AND OBJECTIVES: Economic growth of Sri Lanka has increased the number of motor vehicles. Fuel stations employing more fuel handlers have been established to cope with the demand. The long working hours with exposure to hydrocarbon fuels result in adverse health effects and this study was done to assess the cardiovascular autonomic functions (ANF) including heart rate variations (HRV). METHOD: Fifty fuel handlers from the Gampaha district of Sri Lanka (19-65 years; all were males) from 7 fuel stations were recruited using consecutive sampling and compared with 46 age and gender matched individuals without occupational exposure to fuel (controls). Demographic data were collected after obtaining informed written consent and systematic examination was conducted. ANF assessment and HRV assessment were performed using validated protocols. RESULTS: There were no significant differences in age, weight, height or the BMI among the study and the control populations (p>0.05). Both systolic blood pressure (BP) (Mann Whitney U (MW)= 743.5, p=0.003), diastolic BP (MW= 686.5, p=0.001) and Valsalva ratio (MW= 874.00, p=0.043) were significantly higher among the fuel handlers compared to the controls. Rise in DBP in sustained handgrip, a sympathetic parameter was significantly higher among controls (MW= 863.00, p=0.049). Among HRV parameters, standard deviation of RR intervals was higher among the fuel handlers compared to controls (MW=842.QO, p=0.034). Parasympathetic parameters correlated with exposure hours per week (p<0.05). CONCLUSION: Altered sympathetic: parasympathetic balance was observed among the fuel handlers with a parasympathetic predominance suggesting that autonomic functions are affected on expo sure to air pollution and hydrocarbons.Item Confirmation of mosaic trisomy 22 in an infant with failure to thrive(Sri Lanka College of Paediatricians, 2018) Dayasiri, K.C.; de Silva, D.; Weerasekara, K.No Abstract availableItem Characteristic dental pattern with hypodontia and short roots in Fraser Syndrome(Wiley-Liss, 2020) Kunz, F.; Kayserili, H.; Midro, A.; de Silva, D.; Basnayake, S.; Güven, Y.; Borys, J.; Schanze, D.; Stellzig-Eisenhauer, A.; Bloch-Zupan, A.; Zenker, M.ABSTRACT:Fraser syndrome (FS) is a rare autosomal recessive multiple congenital malformation syndrome characterized by cryptophthalmos, cutaneous syndactyly, renal agenesis, ambiguous genitalia, and laryngotracheal anomalies. It is caused by biallelic mutations of FRAS1, FREM2, and GRIP1 genes, encoding components of a protein complex that mediates embryonic epithelial-mesenchymal interactions. Anecdotal reports have described abnormal orodental findings in FS, but no study has as yet addressed the orodental findings of FS systematically. We reviewed dental radiographs of 10 unrelated patients with FS of different genetic etiologies. Dental anomalies were present in all patients with FS and included hypodontia, dental crowding, medial diastema, and retained teeth. A very consistent pattern of shortened dental roots of most permanent teeth as well as altered length/width ratio with shortened dental crowns of upper incisors was also identified. These findings suggest that the FRAS1-FREM complex mediates critical mesenchymal-epithelial interactions during dental crown and root development. The orodental findings of FS reported herein represent a previously underestimated manifestation of the disorder with significant impact on orodental health for affected individuals. Integration of dentists and orthodontists into the multidisciplinary team for management of FS is therefore recommended. KEYWORDS: Fraser syndrome; dental roots; hypodontia; orodental health; taurodontism.