Janaka de Silva

Liquid chromatography-tandem mass spectrometry method for the simultaneous quantitative determination of the organophosphorus pesticides dimethoate, fenthion, diazinon and chlorpyrifos in human blood.

Simultaneous determination of the organophosphorus pesticides dimethoate, fenthion, diazinon and chlorpyrifos in human blood by HPLC-tandem mass spectrometry was developed and validated. The pesticides were extracted by a simple one-step protein precipitation procedure. Chromatography was performed on a Luna C(18) (30mmx2.0mm, 3microm) column, using a step-gradient at a flow rate of 0.4ml/min. The assay was linear from 0.5 to 100ng/ml (r(2)>0.992, n=24) for all pesticides. The inter- and intra-day accuracy and precision for the method was 96.6-106.1% and <10%, respectively. The lower limit of quantification was 0.5ng/ml. In conclusion, the method described displays analytical performance characteristics that are suitable for the quantification of these pesticides in cases of acute poisoning.

Fetal effects of environmental exposure of pregnant women to organophosphorus compounds in a rural farming community in Sri Lanka

Background. The possible deleterious effects of low-grade, chronic environmental and occupational exposure to organophosphorus compounds (OPCs) are not well documented. Objective. To investigate the possible effects of low-level, chronic exposure of pregnant mothers to OPCs on the fetus by measuring OPC levels, and using markers of OPC exposure, oxidative stress and oxidative tissue damage. Methods. Toxicity was assessed by measuring (i) OPC levels in breast milk and plasma from maternal and cord blood using gas chromatography, (ii) maternal and fetal butyrylcholinesterase (BChE) activity using inhibition assays, (iii) antioxidant status of the fetus using superoxide dismutase activity assays, (iv) oxidative stress in the fetus by determining malondialdehyde (MDA) concentrations, and (v) examining for fetal DNA fragmentation using electrophoresis. Samples were obtained from consenting mothers living in a farming community in southern Sri Lanka at the end of the pesticide spray season (study group) and just before the commencement of the spray season (in-between spray season; control group). Results. Organophosphate residues were detected in only two subjects (chlorpyrifos in maternal and cord blood of one during the spray season and dimethoate in breast milk of another during the in between spray season), but the test employed was capable of only detecting concentrations above 0.05mg/l. However, cord blood obtained during the spray season showed significant inhibition of BChE activity, increased oxidative stress and more DNA fragmentation when compared with cord blood obtained during the in-between spray season. Conclusions. Inhibition of cord blood BChE activity indicates fetal exposure to organophosphorus compounds during times when there is a high probability of environmental drift. This provides a plausible explanation for the increased oxidative stress and high DNA fragmentation in the fetus. Long-term outcomes of such exposures are unknown.

Comparison of a composite symptom score assessing both symptom frequency and severity with a score that assesses frequency alone: a preliminary study to develop a practical symptom score to detect gastro-oesophageal reflux disease in a resource-poor setting

Background There is a need for a practical instrument to screen for gastro-oesophageal reflux disease (GORD) in epidemiological studies. Objectives To develop a practical score to detect GORD and compare assessment of both symptom frequency and severity with frequency alone. Methods One hundred patients with upper gastrointestinal symptoms and 150 volunteers with no such past history faced an interviewer-administered questionnaire assessing seven symptoms, graded for frequency and severity. Two scores were generated. Score 1, the sum of frequency of symptoms and score 2, the sum of products of frequency and severity of each. Internal consistency, test–retest reliability and criterion validity against 24-h pH monitoring were assessed. Cut-off scores were generated by receiver operating characteristic curves using scores of half the volunteers and patients selected randomly and validated on the other half. Results Cut-off scores and area under the curve for score 1 were ≥10.5 and 0.93, and score 2 were ≥12.5 and 0.93, respectively. The sensitivity and specificity of diagnosing the disease in the remaining participants using score 1 was 89.7 and 92.4% and score 2 was 93.8 and 94.0%, respectively. The instrument had good internal consistency (Cronbach &agr; = 0.73) and reliability (intraclass correlation coefficient of scores 1 and 2 were 0.94 and 0.95, respectively). Score 2 showed better correlation with 24-h pH monitoring parameters (Spearmans rank correlation, P = 0.01). Conclusion Our score is valid, reliable and can detect GORD with high sensitivity and specificity. A score assessing both frequency and severity of symptoms correlates better to an objective measure of GORD.

Diffuse-Type Hepatoma: A grave prognostic marker

Background: Data on diffuse-type hepatocellular carcinoma (HCC) are rare. HCC in Sri Lanka is rising, and the majority is related to nonalcoholic fatty liver disease. This study was planned to compare nodular- and diffuse-type HCC in this cohort. Methods: CT scans of 227 patients with HCC negative for infective hepatitis were analyzed and grouped as nodular and diffuse from July 2011 to July 2014. Diffuse-type cancer was defined as a tumor without convex/distinct margin, diffusely infiltrating the hepatic parenchyma. There were 45 (20%) cases. The baseline liver functions, etiology, treatment, and the outcome were compared with nodular-type cancers. Stage III diffuse cancers were matched with 2 stage III nodular cancers looking at the T stage and background liver. Results: There was no difference in the age (63 vs. 62 years, p = 0.937) and gender. Diffuse cancers had a low BMI (24 vs. 22, p = 0.009), a higher alpha fetoprotein (AFP) level (p < 0.001), a higher incidence of major vascular invasion (14 vs. 80%, p < 0.001), and a history of significant alcohol consumption (39 vs. 67%, p = 0.001). The baseline liver functions were similar in diffuse and nodular cancers. A large proportion (27 vs.77%, p < 0.001) of diffuse cancers were not candidates for active treatment. Overall survival was poor in the diffuse type (4.7 vs. 25 months, p < 0.001). Diffuse-type stage III cancers had a poor survival compared to matched nodular cancers (2.5 vs. 15.8 months, p = 0.001). Conclusion: HCC without a background of infective hepatitis were common in our cohort. These tumors are associated with high AFP levels, major vascular invasion, and a poor prognosis.

W1071 Peristaltic Dysfunction in Asthma is Secondary to Increased Gastro-Oesophageal Reflux

AGA Poster Session Abstract (W1071) Digestive Disease Week (DDW), May 1- 5, 2010, New Orleans, LA

T2018 A Composite Symptom Score Using Frequency and Severity Correlates Better to An Objective Measure of Gastro-Oesophageal Reflux Disease (GERD) Than One Scoring Frequency of Symptoms Alone

AGA Poster Session Abstract (T2018) Digestive Disease Week (DDW), May 17 – 22, 2008. San Diego, California