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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty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 A Diagnostic scoring model for Leptospirosis in resource limited settings(Public Library of Science, 2016) Rajapakse, S.; Weeratunga, P.; Niloofa, R.; Fernando, N.; de Silva, N.L.; Rodrigo, C.; Maduranga, S.; Nandasiri, N.; Premawansa, S.; Karunanayake, L.; de Silva, H.J.; Handunnetti, S.Leptospirosis is a zoonotic infection with significant morbidity and mortality. The clinical presentation of leptospirosis is known to mimic the clinical profile of other prevalent tropical fevers. Laboratory confirmation of leptospirosis is based on the reference standard microscopic agglutination test (MAT), direct demonstration of the organism, and isolation by culture and DNA detection by polymerase chain reaction (PCR) amplification. However these methods of confirmation are not widely available in resource limited settings where the infection is prevalent, and reliance is placed on clinical features for provisional diagnosis. In this prospective study, we attempted to develop a model for diagnosis of leptospirosis, based on clinical features and standard laboratory test results. METHODS: The diagnostic score was developed based on data from a prospective multicentre study in two hospitals in the Western Province of Sri Lanka. All patients presenting to these hospitals with a suspected diagnosis of leptospirosis, based on the WHO surveillance criteria, were recruited. Confirmed disease was defined as positive genus specific MAT (Leptospira biflexa). A derivation cohort and a validation cohort were randomly selected from available data. Clinical and laboratory manifestations associated with confirmed leptospirosis in the derivation cohort were selected for construction of a multivariate regression model with correlation matrices, and adjusted odds ratios were extracted for significant variables. The odds ratios thus derived were subsequently utilized in the criteria model, and sensitivity and specificity examined with ROC curves. RESULTS: A total of 592 patients were included in the final analysis with 450 (180 confirmed leptospirosis) in the derivation cohort and 142 (52 confirmed leptospirosis) in the validation cohort. The variables in the final model were: history of exposure to a possible source of leptospirosis(adjusted OR = 2.827; 95% CI = 1.517-5.435; p = 0.001) serum creatinine > 150 micromol/l (adjusted OR = 2.735; 95% CI = 1.374-4.901; p = 0.001), neutrophil differential percentage > 80.0% of total white blood cell count (adjusted OR 2.163; 95% CI = 1.309-3.847; p = 0.032), serum bilirubin > 30 micromol/l (adjusted OR = 1.717; 95% CI 0.938-3.456; p = 0.049) and platelet count < 85,000/mm3 (adjusted OR = 2.350; 95% CI = 1.481-4.513; p = 0.006). Hosmer-Lemeshow test for goodness of fit was 0.931. The Nagelkerke R2 was 0.622. The area under the curve (AUC) was noted as 0.762. A score value of 14 reflected a sensitivity of 0.803, specificity of 0.602, a PPV of 0.54, NPV of 0.84, a positive LR of 2.01 and a negative LR of 0.32. CONCLUSIONS: The above diagnostic model for diagnosis of leptospirosis is suggested for use in clinical settings. It should be further validated in clinical practice.Item Mechanism-specific injury biomarkers predict nephrotoxicity early following glyphosate surfactant herbicide (GPSH) poisoning(Elsevier, 2016) Mohamed, F.; Endre, Z.H.; Pickering, J.W.; Jayamanne, S.; Palangasinghe, C.; Shahmy, S.; Chathuranga, U.; Wijerathne, T.; Shihana, F.; Gawarammana, I.; Buckley, N.A.Acute kidney injury (AKI) is common following glyphosate surfactant herbicide (GPSH) self-poisoning. Serum creatinine (sCr) is the most widely used renal biomarker for diagnosis of AKI although a recent study in rats suggested that urinary kidney injury molecule-1 predicted AKI earlier and better after GPSH-induced nephrotoxicity. We explored the utility of a panel of biomarkers to diagnose GPSH-induced nephrotoxicity in humans. In a prospective multi-centre observational study, serial urine and blood samples were collected until discharge and at follow-up. The diagnostic performance of each biomarker at various time points was assessed. AKI was diagnosed using the Acute Kidney Injury Network (AKIN) definitions. The added value of each biomarker to sCr to diagnose AKI was assessed by the integrated discrimination improvement (IDI) metric. Of 90 symptomatic patients, 51% developed AKI and 5 patients who developed AKIN ≥ 2 died. Increased sCr at 8 and 16 hours predicted moderate to severe AKI and death. None of the 10 urinary biomarkers tested increased above normal range in patients who did not develop AKI or had mild AKI (AKIN1); most of these patients also had only minor clinical toxicity. Absolute concentrations of serum and urinary cystatin C, urinary interleukin-18 (IL-18), Cytochrome C (CytoC) and NGAL increased many fold within 8 hours in patients who developed AKIN ≥ 2. Maximum 8 and 16 hour concentrations of these biomarkers showed an excellent diagnostic performance (AUC-ROC ≥0.8) to diagnose AKIN ≥ 2. However, of these biomarkers only uCytoC added value to sCr to diagnose AKI when assessed by IDI metrics. GPSH-induced nephrotoxicity can be diagnosed within 24 hours by sCr. Increases in uCytoC and uIL-18 confirm GPSH-induces apoptosis and causes mitochondrial toxicity. Use of these biomarkers may help to identify mechanism specific targeted therapies for GPSH nephrotoxicity in clinical trials.Item Low prevalence of Hepatitis B and C molecular markers in a cohort of Sri Lankan patients with hepatocellular carcinoma(Sri Lanka Medical Association, 2007) Dassanayake, A.S.; Manamperi, A.; Gunawardena, N.K.; Abeyewickreme, W.; de Silva, A.P.; de Silva, H.J.INTRODUCTION: Hepatitis B (HBV) and C (HCV) infections are leading causes of hepatocellular carcinoma (HCC). Although HCV is the predominant aetiological factor in many parts of the world, HBV remains more important in South Asia. Detection of molecular markers is the most reliable means of diagnosing infection. Molecular studies on HBV and HCV infection in HCC have not been performed in Sri Lanka. OBJECTIVES: To investigate the prevalence of HBV and HCV using molecular markers of infection in a cohort of Sri Lankan patients with HCC. DESIGN, SETTING AND METHODS: 34 consecutive patients with HCC were investigated for evidence of HBV and HCV infection. In addition to serology, serum was tested for HBV DNA and HCV RNA by PCR (sensitivity 500 copies/ml serum) and RT-PCR (sensitivity 200 copies/ml serum ) respectively. A detailed clinical work-up, screening for diabetes mellitus and iron studies were also performed. RESULTS: Of the 34 patients, 32 (94%) -were males; median age was 68 years. All had evidence of background cirrhosis. Five had evidence of past or present HBV infection, four were HBV DNA positive, one was anti-HBc positive but HBV DNA negative, and one was HCV RNA positive. In addition, 23 (67%) had a history of alcohol abuse and 18 (52%) had long standing diabetes. None had evidence of haemochromatosis. CONCLUSIONS: Prevalence of HBV and HCV infection was low in this cohort of Sri Lankan patients with HCC. This is in keeping with the low prevalence of these infections in the community.