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FAO specifications for liquid paraquat dichloride SL formulations require the use of an emetic agent to stimulate vomiting within 30 min of ingestion. To date, there is no high-quality evidence of efficacy, despite use of the PP796 emetic since 1979. We first examined the validity of patients' self-reported dose of paraquat ingested by examining the relationship with blood paraquat concentration and time to death for patients ingesting the standard paraquat SL formulation in a Sri Lankan cohort. As a secondary outcome, we assessed whether ingestion resulted in vomiting within 30 min and whether vomiting was associated with good outcome.Patients presenting with paraquat SL self-poisoning were prospectively studied in ten Sri Lankan hospitals in 2003-08. Data on reported dose ingested, incidence and timing of vomiting after ingestion, treatment received, plasma paraquat concentration, and outcome were collected prospectively on presentation to hospital. Time between ingestion and blood sampling was incorporated by covariate adjustment.441 patients were recruited to the case series, presenting a median (IQR) of 3.0 (1.5-8.1] h post ingestion. Outcome was known for 435 patients of whom 322 (74.0%) died within 42 days, a median of 1.3 (0.6-4.4) days post ingestion. Median reported dose ingested was 15 to30 mL. There was a highly significant linear trend between log plasma paraquat and reported dose ingested (Importantly, we found good agreement between reported dose ingested and plasma paraquat concentration, case fatality, and time to death, suggesting that the reported dose is a valid marker for the dose ingested. Vomiting occurred within 30 min for 68.5% of patients, exceeding the characteristics for a purported effective emetic in the FAO specifications. However, vomiting within 30 min was associated with approximately double the risk of death compared to those who did not vomit, larger paraquat ingestions, and higher blood paraquat concentrations. In addition, death occurred in many patients who did not vomit, and the proportion vomiting within 30 min only reached 82.1% for the highest ingested dose group. Overall, we found no evidence of benefit resulting from incorporation of the emetic, suggesting that the current FAO specification is not effective at preventing deaths after ingestion of the paraquat SL formulation.

Ingestion of organophosphate (OP) pesticides is a common method of self-harm in developing countries. Apart from acute cholinergic effects, limited evidence implicates OP poisoning in long-term neurocognitive deficits. However, prospective neurophysiological evidence of long-term deficits is scarce in humans. We aimed to determine long-term cognitive changes of acute OP pesticide self-poisoning in a prospective follow-up study, using event-related potentials (ERPs), an electroencephalographic index of cognitive functioning.We recruited 203 patients (147 men) hospitalised with OP pesticide ingestion (OP group had significantly slower reaction times than the control group on discharge and at 6 weeks, but not at 6 months. On discharge, the OP group also showed significantly prolonged latency of the parietal P3b component, signifying delayed attentional processing. P3b amplitudes were also significantly smaller in the OP group on discharge and at 6 months. Within the OP group, greater clinical severity of poisoning was associated with smaller P3b amplitudes. Early pre-attentive cortical processing (as indexed by N1 ERP component) showed no significant intergroup differences.Acute OP pesticide poisoning was associated with impaired behavioural and neurophysiological indices of selective attention. These deficits outlast the cholinergic phase of intoxication. The neurobehavioral impairment disappears over months, but neurophysiological deficits seem to last even after 6 months. This impairment could potentially compromise the performance and safety of patients for months following clinical recovery.

Abdominal pain is known to be an early clinical predictor of severe systemic Russell's viper (RV) envenomation and is often associated with the later development of coagulopathy and neurotoxicity. The mechanism of abdominal pain is unknown, but we postulated it might be due to intestinal microvascular endothelial gut damage. Gut-toxicity can be detected using the novel biomarker Intestinal Fatty Acid Binding Protein (IFABP). We also wanted to explore the mechanisms and consequences of this toxicity by measuring procalcitonin as a specific marker of sepsis triggered by bacterial endotoxin, and serum cystatin-C (CysC) as a measure of acute kidney injury. We hypothesised that severe gut-injury might lead to gut-barrier failure, translocation of gastrointestinal microorganisms, associated sepsis and systemic inflammatory response syndrome (SIRS), with a possible exacerbation of snake-bite severity, including acute kidney injury that was previously attributed to direct venom effects.Serial plasma samples previously collected from 16 RV envenomations with abdominal pain, 15 RV envenomations without abdominal pain and 25 healthy controls were assayed for IFABP. A subgroup of these RV envenomations were assayed for procalcitonin (The median peak IFABP for RV envenomations was much higher than healthy controls [3703.0 pg/mL (IQR 2250.1-13702.0 pg/mL) vs. 270.1 pg/mL (IQR 153.5-558.0 pg/mL) (IFABP is significantly elevated indicating enterocyte damage occurs in RV envenomation. IFABP correlated with markers of sepsis (procalcitonin) and acute kidney injury (serum CysC) suggesting that enterocyte damage resulting in translocation of microbial associated molecular patterns (MAMPs) contributes to RV envenomation associated SIRS and sepsis.

MicroRNAs in biofluids are potential biomarkers for detecting kidney and other organ injuries. We profiled microRNAs in urine samples from patients with Russell’s viper envenoming or acute self-poisoning following paraquat, glyphosate, or oxalic acid [with and without acute kidney injury (AKI)] and on healthy controls. Discovery analysis profiled for 754 microRNAs using TaqMan OpenArray qPCR with three patients per group (12 samples in each toxic agent). From these, 53 microRNAs were selected and validated in a larger cohort of patients (Russell’s viper envenoming = 53, paraquat = 51, glyphosate = 51, oxalic acid = 40) and 27 healthy controls. Urinary microRNAs had significantly higher expression in patients poisoned/envenomed by different nephrotoxic agents in both discovery and validation cohorts. Seven microRNAs discriminated severe AKI patients from no AKI for all four nephrotoxic agents. Four microRNAs (miR-30a-3p, miR-30a-5p, miR-92a, and miR-204) had > 17 fold change (p 0.72. Pathway analysis of target mRNAs of these differentially expressed microRNAs showed association with the regulation of different nephrotoxic signaling pathways. In conclusion, human urinary microRNAs could identify toxic AKI early after acute injury. These urinary microRNAs have potential clinical application as early non-invasive diagnostic AKI biomarkers.

Pesticide self-poisoning is a global clinical and public health problem. While self-poisoning with insecticides and herbicides has been extensively studied, there is minimal literature on acute fungicide self-poisoning. We aimed to study the clinical course and outcome of fungicide self-poisoned patients recruited to a prospective cohort in Sri Lanka. We conducted a prospective study of patients presenting with fungicide self-poisoning to nine hospitals in Sri Lanka between 2002 and 2020. Patients were enrolled by clinical research assistants, with clinical outcomes being recorded at regular review for each patient. We identified 337 cases of self-poisoning with fungicides (alcohol as only co-ingestant), including 28 different fungicides across 5 different fungicide classes. Median time from ingestion to examination was 3.1 (1.8–5.7) h. Nearly all presented to hospital fully conscious (GCS 15, 15–15)— only 27 patients (8.0%) presented with reduced GCS (n = 2), propamocarb and pyraclostrobin. Fungicide self-poisoning appears to be less hazardous than insecticide or herbicide self-poisoning, with a substantially lower case fatality in the same cohort. Edifenphos is an exception to this ‘less toxic’ rule; as a WHO Class Ib highly hazardous pesticide, we recommend its withdrawal from, and replacement in, global agricultural practice. Propamocarb should be listed in the WHO hazard classification as propamocarb hydrochloride to reflect the higher toxicity of the common agricultural formulation. Pyraclostrobin currently has no WHO classification; one is urgently required now that its ingestion has now been linked the death of a patient. Additional prospective clinical data on fungicide self-poisoning is required to expand knowledge on the effects of these diverse compounds.

Self-poisoning with imidacloprid has been previously shown to have low toxicity in humans. Since 2007 newer formulations of Imidacloprid with unknown solvents have been introduced and the potential clinical consequences of these products have not been described.Clinical and demographic data were prospectively collected from admissions following oral ingestion of imidacloprid from seven hospitals in Sri Lanka. Data was collected from 2002 to 2007 in an already published study. We compared this data on poisonings collected from 2010 to 2016 following the introduction of new formulations of imidacloprid.From 2002-2007, there were 56 patients with ingestion to imidacloprid compared to 67 patients post 2010 The median time to presentation prior to 2007 was 4 h (IQR 2.3-6.0 hrs) and post 2010 was only 2.0 hr (IQR 1.5 to 3.1 hrs). The median amount ingested was 15 ml (IQR 10.0-50.0mls) prior to 2007 and 27.5mls (IQR 5.0-71.8mls) post 2010. In both studies most patients developed non-specific symptoms including nausea, vomiting, epigastric pain and headache. However, prior to 2007 only 1.9% of the cohort required mechanical ventilation due to respiratory failure and there were no reported deaths. In contrast, post 2010; deaths occurred in 3.0% of the cohort and 6.0% required mechanical ventilation for respiratory failure. The cause of mortality was due to one case of cardiorespiratory failure and the other due to a prolonged admission complicated with lobar pneumonia leading to decompensated liver failure on the background of undiagnosed liver cirrhosis.Although acute exposure to imidacloprid is usually associated with mild non-specific symptoms, since the introduction of new formulations of imidacloprid, the toxic profile has changed with reported cases of death as well as an increase in cases requiring mechanical ventilation. The change in toxicity could be due to the solvents used in the newer formulations but also due to higher dose of imidacloprid described in our latter cohort. Further research into these solvents needs to be done and continued toxicovigilance is required.

Acute kidney injury (AKI) is the most serious clinical manifestation of the Sri Lankan hump-nosed pit viper (Hypnale spp.) bites. Thrombotic microangiopathy (TMA) is increasingly recognized in asso...

Some epidemiological evidence implicates acute organophosphate (OP) pesticide poisoning in long-term neurocognitive deficits. However, no study has prospectively followed up poisoned patients long-term from the time of intoxication. We aimed to determine whether clinically significant acute OP self-poisoning leads to subacute and chronic neurocognitive deficits, in a prospective follow up study.Employing Mini Mental State Examination, Digit Span and Cambridge Neuropsychological Test Automated Battery (CANTAB), we compared multiple cognitive functions in 222 patients hospitalized with acute OP pesticide self-poisoning with a control group of 52 patients hospitalized with paracetamol overdose, at three time points: on discharge following clinical recovery, 6 weeks and 6 months post-ingestion. Intergroup comparisons at each time point were done in multiple regression models, adjusting for sex, age, education and psychiatric comorbidities. OP within-group analysis was done to determine a dose-response relationship.After adjusting for covariates, the OP poisoned group had significantly poorer working memory (Digit Span) and episodic memory (CANTAB Paired Associates Learning); impaired spatial planning (CANTAB Stocking of Cambridge); and slower response speed in the sustained attention task (CANTAB Rapid Visual Information Processing), in the post-discharge assessment. Only working memory and episodic memory measures were impaired in the OP group at 6 weeks, whereas no significant intergroup differences were observed at 6 months. The OP subgroup who had complete red cell acetylcholinesterase inhibition on admission had poorer episodic memory when tested post-discharge than those who had partial inhibition, but no significant subgroup differences were observed at 6 weeks or 6 months.Acute OP pesticide poisoning may cause neuropsychological impairment that outlasts the cholinergic phase on a subacute time scale; but does not cause measurable chronic neuropsychological deficits.

Organophosphorus (OP) insecticide poisoning is a significant health problem in South Asian countries. Although cholinergic receptors are present at the junction between photoreceptors and the retinal pigment epithelium (RPE), human studies of the effects of OP poisoning on the visual pathways are very few. This study aims to demonstrate the pattern of changes in retina and post retinal pathways in patients with acute OP poisoning using visual electrophysiological tests.This is an observational, cross-sectional study conducted at the Neurophysiology Unit, Teaching Hospital, Peradeniya, Sri Lanka. We tested 16 patients recovered from cholinergic phase, at least 24 h after deatropinization and within 8 weeks of OP ingestion. We assessed the functional integrity of the photoreceptors and ganglion cells of the macula by pattern electroretinography (PERG); RPE by electro-oculography (EOG); and post retinal pathways by pattern reversal visual evoked potentials (PR-VEP). Latencies and amplitudes of PR-VEP and PERG, light peak (LP), dark trough (DT) and Arden ratio of EOG were determined in patients and compared with 16 controls using the Mann-Whitney U test.Of the 16 OP-poisoned patients (median age of 37 ± IQR 20 years), six (37.5%) had reduced Arden ratio with reference to the International Society of Clinical Electrophysiology of Vision cut-off value of 1.7. The median Arden ratio in patients (1.69 ± IQR 0.36) was significantly lower compared to controls (1.90 ± IQR 0.4). The median latencies and amplitudes of PR-VEP or PERG were not significantly different between patients and controls. However, three patients had prolonged P100 latencies in PR-VEP and one had prolonged P50 latency in PERG.Acute OP poisoning seems to affect the functions of the RPE and the visual electrophysiological changes outlast the cholinergic phase. Limited evidence suggests that photoreceptors of the macula region and post retinal pathway might be affected in some patients.

Aim Alcohol is a commonly co-ingested compound during self-poisoning with pesticides. Clinical experiences suggest alcohol co-ingestion (or withdrawal) makes patient management more difficult after self-poisoning and may contribute to poor clinical outcomes. We aimed to systematically review the world literature to explore the relationship between alcohol co-ingestion and outcome in pesticide self-poisoning. Methods We searched 13 electronic databases and Google scholar, conducted citation searching and a review of reference lists to find studies which investigated the relationship of alcohol with clinical outcome of pesticide self-poisoning in different countries. Thirteen studies, including 11 case series/reports and two cohort studies were considered for inclusion. Results Meta-analysis showed that alcohol co-ingestion in pesticide self-poisoning was associated with increased risk of death [odds ratio (OR) 4.9, 95% confidence interval (CI) 2.9–8.2 P Conclusions This systematic review indicates that alcohol co-ingestion may worsen clinical outcome in pesticide self-poisoning.

Self-poisoning with organophosphorus (OP) insecticides is an important means of global self-harm. The insecticides are formulated with solvents that may also contribute to toxicity. We set up a study to detect changes in osmolal and anion gaps following ingestion of OP insecticides. We recruited consecutive patients admitted to a Teaching Hospital, Sri Lanka, with a history of OP self-poisoning. The osmolal and anion gaps were calculated on admission and at 4, 24 and 72 h post-ingestion together with ethanol concentration. Forty-nine patients were recruited (28 profenofos, 10 diazinon, one coumaphos, one chlorpyrifos, one phenthoate and eight unknown OP). Only modest increases in osmolal and anion gaps were noted. Small rises in osmolal gap above the upper limit of normal were noted in 16/49 (32.7%) of all cases, 9/28 (32.1%) profenofos cases and 4/10 (40.0%) diazinon cases. The anion gap was raised in 24/49 (49.0%) of all cases, 15/28 (53.6%) profenofos cases and 5/10 (50.0%) diazinon cases. We observed a trend for a fall in osmolal gap during the first 24 h, followed by an increase up to 72 h. There was no correlation between the anion gap and serum lactate concentration, indicating that a lactic acidosis was not responsible for the anion gap. Formate, which could have explained the increased gap, was not detected in any of the samples; ketoacids (beta-hydroxybutyrate and acetoacetate) were not measured. This pilot study found that profenofos and diazinon poisoning caused only modest increases in the osmolal and anion gaps in a minority of cases.

Human envenoming from the bite of the abundant hump nosed pit viper (Hypnale hypnale) (HNPV) is a frequent occurrence with victims experiencing unpleasant and sometimes life-threatening consequences. Regrettably, our therapeutic armamentarium remains limited. Further, clinico-pathology, treatment and management measures in HNPV envenomed dogs are under recognized. Prospective investigations were performed to assess the clilinico-pathology and management options for HNPV envenomed dogs brought to the University of Peradeniya’s Veterinary Teaching Hospital from January, 2012 to March 2018. We recorded the local and systemic clinical manifestations, hematological and urinary abnormalities of 78 dogs in which HNPV bite had been witnessed by the owner. Mild swelling, extensive swelling, hemorrhagic blistering and hemorrhagic bullae at the site of bite were observed in 59%, 31%, 6% and 4% of the dogs, respectively. Some dogs were subjected to surgical excision of necrotized tissue including limb amputation. We observed the following systemic clinical effects in envenomed dogs: neurotoxicity (13%), acute kidney injuries (AKI) (14%) and coagulopathy (16%). All dogs showed leukocytosis with mean white blood cell count of 25.25×103/µL. Mild anemia and thrombocytopenia were detected in 29% of the dogs. There was a significant correlation between extent of local tissue injuries with length of hospitalization (LH). The mean time of coagulopathy observed was 21.3 hours (IQR: 8-48 hours). In coagulopathic dogs, there was a strong correlation between LH and extent of local tissue injury (rs = 0.7751, P rs = 1.0, P rs = 0.4712, P p=0.0013). Lack of specific AVS for HNPV envenoming provided an opportunity to study the remaining treatment options. Therefore, the study allowed the identification of local and systemic effects, hematological abnormalities, possible auxiliary treatments and drawbacks of management measures for envenomed dogs.

Context: Thrombotic microangiopathy (TMA) resulting in acute kidney injury (AKI) is an important complication of venomous snakebites. We aimed to describe TMA secondary to Russell’s viper (Daboia r...

The hump-nosed pit viper Hypnale hypnale is responsible for a high number of snakebite cases in southwestern India and Sri Lanka. Although most patients only develop local signs and symptoms of envenoming, there is a growing body of evidence indicating that these envenomings may be associated with systemic alterations, including acute kidney injury. In this study we evaluated the renal toxicity of H. hypnale venom by using a perfused isolated rat kidney system and by assessing cytotoxicity in two different renal tubular cell lines in culture. The venom caused alterations in several renal functional parameters, such as reduction on perfusion pressure, renal vascular resistance, and sodium and chloride tubular transport, whereas glomerular filtration rate and urinary flow initially decreased and then increased after venom perfusion. In addition, this venom was cytotoxic to proximal and distal renal tubular cells in culture, with predominance of necrosis over apoptosis. Moreover, the venom affected the mitochondrial membrane potential and induced an increment in reactive oxygen species in these cells. Taken together, our results demonstrate a nephrotoxic activity of H. hypnale venom in these experimental models, in agreement with clinical observations.

Summary Background Pesticide poisoning is among the most common means of suicide globally, but can be prevented with regulation of the most hazardous agents. We aimed to compare the lethality of pesticides ingested by our cohort, seek evidence on variation between human and regulatory animal toxicity, and establish change over time in the case fatality of individual pesticides in Sri Lanka. Methods We examined the case fatality of agricultural pesticides in a prospective cohort in nine hospitals serving rural populations in Sri Lanka. We included all patients (>11 years) who had presented to a South Asian Clinical Toxicology Research Collaboration study hospital during the study period. Patients were enrolled by clinical research assistants and were regularly reviewed. Identification of the ingested pesticide was generally on the basis of history or positive identification of the container, supported by nested blood analysis. Findings From March 31, 2002, to Dec 31, 2019, 34 902 patients (median age 29 years [IQR 21–40]; 23 060 [66·1%] male) presented with a possible or known pesticide self-poisoning. We identified 23 139 specific pesticides that were ingested. Poisoning was fatal in 2299 (6·6%) patients. Case fatality varied greatly from 0·0% (several substances) to 41·8% (paraquat). The three most toxic agents (ie, paraquat, dimethoate, and fenthion) were banned between 2008 and 2011. Since 2013, the five agents causing the most deaths (ie, profenofos, propanil, fenobucarb, carbosulfan, and quinalphos) had a case fatality of 7·2–8·6%. A steady decline was seen in overall case fatality of pesticide poisoning (10·5% for 2002–06 to 3·7% for 2013–19), largely attributable to pesticide bans. A modest fall in case fatality for non-banned pesticides was also seen. Interpretation Declines seen in case fatalities of poisonings with non-banned pesticides suggest that medical management improved over time. The human data for acute toxicity of pesticides should drive hazard classifications and regulation. We believe that a global benchmark for registration of pesticides should include a less than 5% case fatality after self-poisoning, which could prevent many deaths and have a substantial effect on global suicide rates. Funding The Wellcome Trust and the National Health and Medical Research Council of Australia. Translations For the Sinhala and Tamil translations of the abstract see Supplementary Materials section.

BACKGROUND: Adhesive capsulitis is a debilitating condition which causes the capsule of the gleno-humeral joint to thicken and contract progressively. The effectiveness of various non-operative methods has been demonstrated to improve the pain, range of motion (ROM) and functional status of patients with adhesive capsulitis. OBJECTIVE: This study aims to review recent evidence on the efficacy of physiotherapy interventions in the treatment of adhesive capsulitis. METHODS: PubMed, Physiotherapy Evidence Database (PEDro), Science Direct and Cochrane databases were searched for studies published since 2013. The search terms included: Frozen shoulder, adhesive capsulitis, physical therapy, rehabilitation, manual therapy, mobilization, exercise, education, and electrotherapy. The search was limited to studies published in English and studies that used human subjects. RESULTS: Quality scores of 33 articles were reviewed according to the Sackett’s critical appraisal criteria and the grades of recommendation were determined for physiotherapy interventions used in the studies. CONCLUSION: The empirical evidence suggests that certain physical therapy techniques and modalities are strongly recommended for pain relief, improvement of ROM, and functional status in patients with adhesive capsulitis, while others are either moderately or mildly recommended. However, the efficacy of one treatment modality over another is uncertain. The poor methodological rigors demonstrated in most of the reviewed studies emphasize the urgent need of properly conducted, adequately sampled randomized controlled trials with adequate follow up to determine the superior combination of treatment.

Acute kidney injury (AKI) is the most serious clinical manifestation of the Sri Lankan hump-nosed pit viper (We conducted a prospective observational study of suspected viper bites and included 103 confirmed cases ofTen patients developed AKI: seven AKI stage 1 and three AKI stage 3. Ten patients (10%) developed thrombocytopaenia while 11 (11%) had MAHA. All three AKI stage 3 had thrombocytopaenia and MAHA fulfilling the criteria for TMA. Two of them presented with oliguria/anuria and all three required haemodialysis. Serum creatinine within 4 h post-bite was the best predictor of AKI with AUC-ROC of 0.83 (95% CI: 0.67-0.99) and was no better within 8 h of the bite.We found that AKI is uncommon in

Introduction: Gloriosa superba is a flowering plant that contains colchicine. Deliberate self-poisoning with this plant in Sri Lanka is common and potentially fatal. The objective of this study was...

Background Detection and quantification of snake venom in envenomed patients’ blood is important for identifying the species responsible for the bite, determining administration of antivenom, confirming whether sufficient antivenom has been given, detecting recurrence of envenoming, and in forensic investigation. Currently, snake venom detection is not available in clinical practice in Sri Lanka. This study describes the development of enzyme immunoassays (EIA) to differentiate and quantify venoms of Russell’s viper (Daboia russelii), saw-scaled viper (Echis carinatus), common cobra (Naja naja), Indian krait (Bungarus caeruleus), and hump-nosed pit viper (Hypnale hypnale) in the blood of envenomed patients in Sri Lanka. Methodology / Principal findings A double sandwich EIA of high analytical sensitivity was developed using biotin-streptavidin amplification for detection of venom antigens. Detection and quantification of D. russelii, N. naja, B. caeruleus, and H. hypnale venoms in samples from envenomed patients was achieved with the assay. Minimum (less than 5%) cross reactivity was observed between species, except in the case of closely related species of the same genus (i.e., Hypnale). Persistence/ recurrence of venom detection following D. russelii envenoming is also reported, as well as detection of venom in samples collected after antivenom administration. The lack of specific antivenom for Hypnale sp envenoming allowed the detection of venom antigen in circulation up to 24 hours post bite. Conclusion The EIA developed provides a highly sensitive assay to detect and quantify five types of Sri Lankan snake venoms, and should be useful for toxinological research, clinical studies, and forensic diagnosis., Author summary Snakebite is a major medical and public health problem in tropical agricultural world. Detection of the type of snake venom and measurement of venom levels in blood are important for snakebite research, selecting the appropriate antivenom, and assessing venom levels in blood at the clinical setting. Currently, a snake venom detection platform is not available in clinical practice in Sri Lanka. This study aimed to develop a double sandwich enzyme immunoassays (EIA) to differentiate and quantify venoms of Russell’s viper (Daboia russelii), saw-scaled viper (Echis carinatus), common cobra (Naja naja), Indian krait (Bungarus caeruleus), and hump-nosed pit viper (Hypnale hypnale) in blood samples of envenomed patients in Sri Lanka. The EIA developed used biotin-streptavidin amplification for detection of venom antigens and showed high analytical sensitivity. The assay allowed the quantification of venoms of the five species in blood samples from envenomed patients. Low level of cross reactivity was noted between species, except in the case of closely related Hypnale species. The presence of D. russelii venom after antivenom treatment is reported, a finding that has implications in the dosing of antivenom in these envenomings. Lack of specific antivenom for H. hypnale envenoming offered an opportunity of study the remaining venom antigen in circulation up to 24 hr post bite. The EIA developed constitutes a useful tool to detect and quantify the five types of Sri Lankan snake venoms, and should be useful for research purposes, as well as for the diagnosis and therapy evaluation of clinical cases of envenomings in this country, and for forensic purposes.

Previous studies on human acute kidney injury (AKI) following poisoning with potassium permanganate/oxalic acid (KMnO4/H2C2O4), paraquat, and glyphosate surfactant herbicide (GPSH) have shown rapid and large increases in serum creatinine (sCr) that cannot be entirely explained by direct nephrotoxicity. One plausible mechanism for a rapid increase in sCr is oxidative stress. Thus, we aimed to explore biomarkers of oxidative stress, cellular injury, and their relationship with sCr, after acute KMnO4/H2C2O4, paraquat, and GPSH poisonings. Serum biomarkers [sCr, creatine (sCn), cystatin C (sCysC)] and urinary biomarkers [cytochrome C (CytoC), 8-isoprostane (8-IsoPs)] were evaluated in 105 patients [H2C2O4/KMnO4 (N = 57), paraquat, (N = 21), GPSH (N = 27)] recruited to a multicenter cohort study. We used area under the receiver operating characteristics curve (AUC-ROC) to quantify the extent of prediction of moderate to severe AKI (acute kidney injury network stage 2/3 (AKIN2/3)). Patients with AKIN2/3 showed increased levels of CytoC. Early high CytoC predicted AKIN2/3 in poisoning with KMnO4/H2C2O4 (AUC-ROC4−8h: 0.81), paraquat (AUC-ROC4−8h: 1.00), and GPSH (AUC-ROC4−8h: 0.91). 8-Isoprostane levels were not significantly elevated. Reduced sCn and increased sCr/sCn ratios were observed for 48 h post KMnO4/H2C2O4 ingestion. Paraquat exhibited a similar pattern (N = 11), however only 3 were included in our study. Increased CytoC suggests there is mitochondrial injury coupled with energy depletion. The increased sCr within 24 h could be due to increased conversion of cellular creatine to creatinine during the process of adenosine triphosphate (ATP) generation and then efflux from cells. Later increases of sCr are more likely to represent a true decrease in kidney function.

Background: The effects of combined oral contraceptive pills and metformin on glucose and lipid metabolism and androgenic hormone profile of hirsute women with polycystic ovary syndrome (PCOS) are not clearly known. Aims: To determine the effect of ethinylestradiol (35 microg)/cyproterone acetate (2 mg) (EE/CPA) and ethinylestradiol (20 microg)/desogestrel 0.15 mg (EE/DES) alone and in combination with metformin on glucose and lipid metabolism and androgenic hormone profile in hirsute women with PCOS. Settings and Design: This randomised, double-blind, triple dummy study was conducted at the Department of Pharmacology, Faulty of Science, University of Peradeniya, Sri Lanka. Methods and Material: A total of 107 patients with PCOS (Rotterdam Consensus Conference Criteria 2003) having hirsutism of 8 or more in the modified Ferriman-Gallwey Score (mFGS), were randomised to receive four drug therapies (arm A: EE/CPA, arm B: EE/DES, arm C: EE/CPA plus metformin, arm D: EE/DES plus metformin). Body mass index, fasting plasma glucose, area under the curve of the oral glucose tolerance test, fasting serum insulin, serum leptin, fasting lipids, serum total testosterone, serum sex hormone-binding globulin were determined at initiation and 12 months. Homeostasis model assessment of beta cell function (HOMA-β), homeostasis model assessment-estimated insulin resistance (HOMA-IR) and free androgen index were calculated. Statistical analysis was done with two ways ANOVA. Results: There was no significant difference in outcome measures at 12 months between the treatment arms. Within the treatment arms, there was reduction of HOMA-β in arm B, serum leptin in arm C, CHO/HDL ratio in arm D and an increase in total cholesterol and LDL-cholesterol in arms B and C. Conclusions: EE/DES and EE/CPA with and without low-dose metformin did not have a significant overall effect on glucose and lipid metabolism and androgenic hormonal profile in hirsute women with PCOS. However, desogestrel has reduced the beta-cell function and both desogestrel and cyproterone have adversely affected the lipids.

Introduction: Russell’s viper envenoming in dogs is a significant problem in Sri Lanka. The current study focused on investigating clinical profile, laboratory findings of three selected tests and to develop a treatment strategy with Indian polyvalent Anti-Venom Serum (AVS). It was also intended to report adverse effects and complications caused by both Russell's viper venom (RVV) and AVS in Russell’s Viper (RV) envenomed dogs. Objective: To evaluate and report the clinical manifestations, to find out the minimum effective vials of AVS and to record AVS induced adverse reactions of RV envenoming in dogs. Materials and methods: A prospective study was conducted on Russell's viper bitten dogs (n = 65) admitted to the Veterinary Teaching Hospital (VTH) in Sri Lanka. Indian polyvalent AVS was used to treat all the envenomed dogs. The number of vials of AVS that was administered to a patient was decided upon by a second degree polynomial model with a number of vials of AVS in the X axis verses Prothrombine Time (PT), Activated Partial Thromboplastine Time (aPTT) and Clotting Time (CT) in the Y axis respectively. Results: Varying degrees of pain were exhibited by all the victim dogs. Mild swelling and necrosis at the site of bite was seen in 54% (n = 35) and 37% (n = 24) of dogs respectively. Prolonged values of, PT, aPTT and CT were seen from all the RV envenomed dogs. The mean leukocyte count in these dogs was 39.79 × 103/μL (normal range; 4–20 × 103/μL) (IQR:29.05 × 103/μL-45.92 × 103/μL). Statistical analysis showed that the initial vials of 7 AVS would be the minimum required vials. Therefore, a range of 6–15 AVS vials in total were administered to these dogs and in 7.6% (n = 5) of dogs, the results of PT, aPTT and CT became normal with 6 AVS vials at 32–97 minutes. Acute Renal Failure (ARF) was detected from 29% (n = 19) of dogs as a complication. Conclusions: Systemic clinical signs of haemorrhagic lesions, cardio respiratory toxicities were common in Russell's viper envenomed dogs. Initially 6 vials of AVS must be administered. AVS induced reactions were reported commonly. Russell's viper envenoming was found to be lethal in dogs. Keywords: Daboia russelii, Dogs, Anti-Venom serum, Prothrombine time, Activated partial thromboplastine time, Clotting time

Background Deliberate self-poisoning with a combination washing powder containing oxalic acid (H2C2O4) and potassium permanganate (KMnO4) is a significant medical problem in the Southern Province of Sri Lanka. Acute kidney injury (AKI) is a frequent consequence. Biomarkers for early diagnosis of nephrotoxicity could guide appropriate supportive therapies. Methods We investigated the performance of three serum biomarkers and nine urinary biomarkers in 85 patients in an ongoing multicenter prospective cohort study in Sri Lanka exploring AKI following poisoning. Results Sixty two (62/85, 73%) patients developed AKI (acute kidney injury network, AKIN, criteria). Early and rapid increases in serum creatinine (sCr) peaking on day 3 were observed in AKIN stage 2 and 3 patients. In these patients, serum cystatin C (sCysC) rose more gradually but also peaked on day 3. Biomarker concentrations (normalized to urinary creatinine) of urinary albumin (uAlbumin), clusterin (uClusterin), beta-2-microglobulin (uB2M), osteopontin (uOPN), neutrophil gelatinase-associated lipocalin (uNGAL) and kidney injury molecule-1 (uKIM–1) in the AKIN2/3 group increased above the 95th centile concentration of the healthy population. Within 8 h of ingestion, the normalized uAlbumin and sCysC predicted AKIN2/3 with respective area under receiver operating characteristic curve, AUC-ROC values, of 0.94 (95% CI 0.86–1.00) and 0.85 (95% CI 0.76-0.95). Conclusions Urinary albumin was the best performing AKI biomarker following ingestion of H2C2O4/KMnO4. This may reflect glomerular injury and/or proximal tubular injury. The urinary albumin concentrations observed in this study could generally be detected using albumin specific dipstick methods, easily available even in resource poor settings.

Background Dengue is a common arboviral infection with a diverse spectrum of clinical manifestations. Dengue hemorrhagic fever is a more severe form of infection characterized by plasma leak and hemoconcentration. Although hepatic dysfunction is common in dengue illness, massive liver necrosis is rarely reported. Lactic acidosis is a poor prognostic marker in liver failure related to dengue. Management of acute renal injury in dengue hemorrhagic fever due to prolonged shock is challenging as the fluid reabsorption during the recovery phase expands the intravascular volume and precipitates heart failure and pulmonary edema. Case presentation We report the case of a 43-year-old Sri Lankan Sinhalese woman with serologically confirmed dengue fever presenting with evidence of plasma leakage developing acute liver failure evidenced by deranged liver functions, coagulopathy, and altered sensorium and acute kidney injury with anuria. She had elevated serum lactate levels. In addition to the “standard care,” she was managed with intravenously administered N-acetyl cysteine and blood transfusions, even in the absence of bleeding or dropping packed cell volume, targeting a higher packed cell volume anticipating a better oxygenation at tissue level. Continuous veno-venous hemodialysis was employed and continued for 138 hours removing the fluids reabsorbed during the recovery phase to prevent her from developing heart failure and pulmonary edema. She made full recovery with no sequelae. Conclusions N-acetyl cysteine and packed cell transfusion aiming at a higher packed cell volume to maintain adequate tissue perfusion during shock may be beneficial in acute liver failure due to dengue virus. The use of a continuous form of renal replacement such as continuous veno-venous hemodialysis is of paramount importance in managing fluid states in the recovery phase of dengue hemorrhagic fever in those with renal impairment. Interesting observations made in the fluid dynamics during the reabsorption phase need further studies preferably with an animal model.

Dogs (Canis familiaris) have several behavioral characteristics that may contribute to snakebites. Dogs generally are inquisitive, lack ophidiophobia (fear of snakes), and may attack a snake in def...

Context: Intentional self-poisoning with the herbicide paraquat has a very high case-fatality and is a major problem in rural Asia and Pacific. Objectives: We aimed to determine whether the addition of immunosuppression to supportive care offers benefit in resource poor Asian district hospitals. Materials and methods: We performed a randomised placebo-controlled trial comparing immunosuppression (intravenous cyclophosphamide up to 1 g/day for two days and methylprednisolone 1 g/day for three days, and then oral dexamethasone 8 mg three-times-a-day for 14 days) with saline and placebo tablets, in addition to standard care, in patients with acute paraquat self-poisoning admitted to six Sri Lankan hospitals between 1st March 2007 and 15th November 2010. The primary outcome was in-hospital mortality. Results: 299 patients were randomised to receive immunosuppression (147) or saline/placebo (152). There was no significant difference in in-hospital mortality rates between the groups (immunosuppression 78 [53%] vs. placebo 94 [62%] (Chi squared test 2.4, p = .12). There was no difference in mortality at three months between the immunosuppression (101/147 [69%]) and placebo groups (108/152 [71%]); (mortality reduction 2%, 95% CI: −8 to +12%). A Cox model did not support benefit from high-dose immunosuppression but suggested potential benefit from the subsequent two weeks of dexamethasone. Conclusions: We found no evidence that high dose immunosuppression improves survival in paraquat-poisoned patients. The continuing high mortality means further research on the use of dexamethasone and other potential treatments is urgently needed.

Acute kidney injury (AKI) is common following deliberate self-poisoning with a combination washing powder containing oxalic acid (HMultiple measures of change in kidney function were evaluated in 48 consenting patients who had serial sCr and serum cystatin C (sCysC) data available.Thirty-eight (38/48, 79%) patients developed AKI (AKIN criteria). Twenty-eight (58%) had AKIN stage 2 or 3. Initial increases in urine creatinine (uCr) excretion were followed by a substantial loss of renal function. The AKIN stage 2 and 3 (AKIN2/3) group had very rapid rises in sCr (a median of 118% at 24 h and by 400% at 72 h post ingestion). We excluded the possibility that the rapid rise resulted from the assay used or muscle damage. In contrast, the average sCysC increase was 65% by 72 h.In most AKI, sCysC increases to the same extent but more rapidly than sCr, as sCysC has a shorter half-life. This suggests either a reduction in Cystatin C production or, conversely, that the rapid early rise of sCr results from increased production of creatine and creatinine to meet energy demands following severe oxidative stress mediated by H

Background: Poisoning with Gloriosa superba, a plant containing colchicine, is common in Sri Lanka. Objectives: This study was to estimate release of colchicine from 5 g of different parts of Gloriosa superba in simulated gastric and intestinal media, and examine the binding efficacy of activated charcoal (AC) to colchicine within this model. Methods: A USP dissolution apparatus-II was used to prepare samples for analysis of colchicine using HPLC. Results: Cumulative colchicine release from tuber in gastric media at 120 minutes was significantly higher (2883 μg/g) than in intestinal media (1015 μg/g) (p

Essentials Russell's viper envenoming is a major health issue in South Asia and causes coagulopathy. We studied the effect of fresh frozen plasma and two antivenom doses on correcting coagulopathy. Fresh frozen plasma did not hasten recovery of coagulopathy. Low-dose antivenom did not worsen coagulopathy. SUMMARY: Background Russell's viper (Daboia russelii) envenoming is a major health issue in South Asia and causes venom-induced consumption coagulopathy (VICC). Objectives To investigate the effects of fresh frozen plasma (FFP) and two antivenom doses in correcting VICC. Methods We undertook an open-label randomized controlled trial in patients with VICC at two Sri Lankan hospitals. Patients with suspected Russell's viper bites and coagulopathy were randomly allocated (1 : 1) to high-dose antivenom (20 vials) or low-dose antivenom (10 vials) plus 4 U of FFP. The primary outcome was the proportion of patients with an International Normalized Ratio (INR) of < 2 at 6 h after antivenom administration. Secondary outcomes included anaphylaxis, major hemorrhage, death, and clotting factor recovery. Results From 214 eligible patients, 141 were randomized: 71 to high-dose antivenom, and 70 to low-dose antivenom/FFP; five had no post-antivenom blood tests. The groups were similar except for a delay of 1 h in antivenom administration for FFP patients. Six hours after antivenom administration, 23 of 69 (33%) patients allocated to high-dose antivenom had an INR of < 2, as compared with 28 of 67 (42%) allocated to low-dose antivenom/FFP (absolute difference 8%; 95% confidence interval - 8% to 25%). Fifteen patients allocated to FFP did not receive it. Severe anaphylaxis occurred equally frequently in each group. One patient given FFP developed transfusion-related acute lung injury. Three deaths occurred in low-dose antivenom/FFP patients, including one intracranial hemorrhage. There was no difference in recovery rates of INR or fibrinogen, but there was more rapid initial recovery of factor V and FX in FFP patients. Conclusion FFP after antivenom administration in patients with Russell's viper bites did not hasten recovery of coagulopathy. Low-dose antivenom/FFP did not worsen VICC, suggesting that low-dose antivenom is sufficient. NHMRC. Grant Numbers: 631073, 1061041, 1059542

Background Wasp stings are commonly encountered worldwide and result in a variety of clinical manifestations including local and systemic reactions. Neurological and vascular complications are rarely reported following a wasp sting. Case presentation A 69-year-old Sri Lankan Tamil man presented to our hospital with focal neurological deficit following multiple wasp stings; the deficit was confirmed to be an acute infarction on magnetic resonance imaging scan. He was screened for metabolic risk factors which were negative and he had a normal two-dimensional echocardiogram and normal carotid arteries in carotid duplex which excluded potential sources of thromboembolism. Conclusion Treating physicians should be aware of the rare but possible complication of ischemic stroke following a case of wasp sting.

Wistar rats were administered increasing doses of Russell's viper venom (RVV; 0.025–0.4 mg/kg) intraperitoneally to investigate acute kidney injury (AKI) by measuring creatinine (1.5-fold increase in serum creatinine above baseline) and examining kidney histology. Approximately 50% of rats receiving 0.25–0.4 mg/kg venom died within 72 h. An increase in serum creatinine only occurred at a venom dose of 0.4 mg/kg, except in two rats. Acute tubular necrosis, glomerular necrosis, cortical necrosis and interstitial inflammation were observed at venom doses of ≥0.25 mg/kg in 12/36 rats. However, of those 12 rats only four survived to 48 h compared to the 24 rats not developing nephrotoxicity, in which 18 were alive at 48 h. There was poor correlation between histological nephrotoxicity and AKI based on creatinine measurement. The early death in rats with AKI makes this a poor model for studying RVV-induced AKI.

Introduction: Self-poisoning with organophosphorus pesticides (OPs) has high morbidity and mortality. The most toxic OP formulations have been progressively banned in Sri Lanka over the past three ...

Background: A common manifestation of organophosphorus insecticide self-poisoning is prolonged respiratory failure due to neuromuscular junction dysfunction and likely nicotinic receptor ov...

Introduction. Ingestion of organophosphate insecticides (OPIs) is a common method of self-harm and a major clinical problem is Asia. Apart from acute cholinergic effects, OPIs are also claimed to be associated with long-term neurobehavioural deficits. However, neurophysiological evidence for such long-term deficits is scarce in humans. We aimed to assess long-term changes in the pre-attentive (N1) and attentive (P3b) components of auditory event-related potentials (ERPs) following acute OPI self-poisoning. Methods. We recruited 203 patients (147 men) hospitalised following OPI ingestion (OP Group; all had significant red cell cholinesterase inhibition) and 50 patients (23 men) hospitalised with paracetamol overdose (Control Group) as a means of self harm. We recorded their EEG in an auditory oddball task and derived the averaged ERPs. The subjects underwent three testing sessions: on discharge from hospital (around 14 days post-ingestion), 6 weeks and 6 months post-ingestion. We compared the reaction time and ERP indices of the two groups at each time point, adjusting for sex, age, education and psychiatric comorbidities in multiple regression models. Results. After adjusting for covariates, OP Group had significantly slower reaction time than the Control Group on discharge (mean difference [SE] = 65[20] ms, p = 0.001) and at 6 weeks (mean difference [SE] = 45[20] ms, p = 0.024), but not at 6 months. Parietal (PZ) P3b amplitudes were significantly smaller in the OP group on discharge (mean difference [SE] = 2.23[0.84] V, p = 0.009) and at 6 months (mean difference [SE] = 3.34[1.43] V, p = 0.021). P3b latencies or frontal (FZ) N1 component did not show significant intergroup differences. Conclusion. Acute exposure to clinically significant doses of OPIs seem to cause impairment in behavioural and neurophysiological indices of stimulus discrimination, that outlast the cholinergic phase of intoxication. The behavioural impairment seems to disappear over months, but the underlying neurophysiological deficits of attentive processing seem to last even after 6 months post-exposure.