https://ogma.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:15146 Wed 11 Apr 2018 17:11:07 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:30223 In vitro antivenom efficacy studies were compared to rodent lethality studies to test two Indian snake antivenoms (VINS and BHARAT) against four Sri Lankan snakes. In vitro efficacy was tested at venom concentrations consistent with human envenoming. Efficacy was compared statistically for one batch from each manufacturer where multiple vials were available. In binding studies EC₅₀ for all VINS antivenoms were less than BHARAT for D. russelii [553 μg/mL vs. 1371 μg/mL;p=0.016), but were greater for VINS antivenoms compared to BHARAT for N. naja [336 μg/mL vs. 70 μg/mL;p<0.0001]. EC₅₀ of both antivenoms was only slighty different for E. carinatus and B. caeruleus. For procoagulant activity neutralisation, the EC₅₀ was lower for VINS compared to BHARAT - 60 µg/mL vs. 176 µg/mL (p<0.0001) for Russell's viper and 357 µg/mL vs. 6906µg/mL (p<0.0001) for Saw-scaled viper. Only VINS antivenom neutralized in vitro neurotoxicity of krait venom. Both antivenoms partially neutralized cobra and didn't neutralize Russell's viper neurotoxicity. Lethality studies found no statistically significant difference in ED₅₀ values between VINS and BHARAT antivenoms. VINS antivenoms appeared superior to BHARAT at concentrations equivalent to administering 10 vials antivenom, based on binding and neutralisation studies. Lethality studies were inconsistent suggesting rodent death may not measure relevant efficacy outcomes in humans.]]> Wed 11 Apr 2018 16:22:51 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:21161 Daboia russelii) envenoming in Sri Lanka. All patients received Indian F(ab’)₂ snake antivenom manufactured by VINS Bioproducts Ltd. Antivenom concentrations were measured with sandwich enzyme immunoassays. Timed antivenom concentrations were analysed using MONOLIXvs4.2. One, two and three compartment models with zero order input and first order elimination kinetics were assessed. Models were parameterized with clearance(CL), intercompartmental clearance(Q), central compartment volume(V) and peripheral compartment volume(V_P). Between-subject-variability (BSV) on relative bioavailability (F) was included to account for dose variations. Covariates effects (age, sex, weight, antivenom batch, pre-antivenom concentrations) were explored by visual inspection and in model building. There were 75 patients, median age 57 years (40-70y) and 64 (85%) were male. 411 antivenom concentration data points were analysed. A two compartment model with zero order input, linear elimination kinetics and a combined error model best described the data. Inclusion of BSV on F and weight as a covariate on V improved the model. Inclusion of pre-antivenom concentrations or different batches on BSV of F did not. Final model parameter estimates were CL,0.078 Lh⁻¹, V,2.2L, Q,0.178Lh⁻¹ and V_P,8.33L. The median half-life of distribution was 4.6h (10-90%iles:2.6-7.1h) and half-life of elimination, 140h (10^th-90^th percentilesx:95-223h). Conclusion: Indian F(ab’)₂ snake antivenom displayed biexponential disposition pharmacokinetics, with a rapid distribution half-life and more prolonged elimination half-life.]]> Wed 11 Apr 2018 16:20:31 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:14867 Wed 11 Apr 2018 15:51:53 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:28884 Wed 11 Apr 2018 15:45:25 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:14472 Wed 11 Apr 2018 13:49:04 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:27369 13), associated with low fibrinogen [median,<0.01g/L;IQR:<0.01-0.9g/L), low factor V levels [median,<5%;IQR:<5-4%], low factor VIII levels [median,40%;IQR:12-79%] and low factor X levels [median,48%; IQR:29-67%]. There were smaller reductions in factors II, IX and VII over time. All factors recovered over 48h post-antivenom. The median INR remained >3 at 6h post-antivenom but had reduced to <2, by 24h. The aPTT had also returned to close to normal (<50sec) at 24h. Factor VII, VIII and IX levels were unusually high pre-antivenom, median peak concentrations of 393%, 307% and 468% respectively. Pre-antivenom venom concentrations and the INR (r=0.20, p=0.02) and aPTT (r=0.19, p=0.03) were correlated (non-parametric Spearman analysis). Conclusions: Russell's viper coagulopathy results in prolonged aPTT, INR, low fibrinogen, factors V, VIII and X which recover over 48h. Severity of clotting abnormalities was associated with venom concentrations.]]> Wed 11 Apr 2018 11:40:46 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:14373 Wed 11 Apr 2018 10:50:48 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:19519 Wed 11 Apr 2018 09:27:43 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:21860 Tue 26 Sep 2017 14:05:54 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:20168 Tue 24 Aug 2021 14:23:24 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:28062 Daboia russelii) cause unique neuromuscular paralysis not seen in other Russells vipers. Objective: To investigate the time course and severity of neuromuscular dysfunction in definite Russells viper bites, including antivenom response. Methodology: We prospectively enrolled all patients (>16 years) presenting with Russells viper bites over 14 months. Cases were confirmed by snake identification and/or enzyme immunoassay. All patients had serial neurological examinations and in some, single fibre electromyography (sfEMG) of the orbicularis oculi was performed. Results: 245 definite Russells viper bite patients (median age: 41 years; 171 males) presented a median 2.5 h (interquartile range: 1.75-4.0 h) post-bite. All but one had local envenoming and 199 (78%) had systemic envenoming: coagulopathy in 166 (68%), neurotoxicity in 130 (53%), and oliguria in 19 (8%). Neurotoxicity was characterised by ptosis (100%), blurred vision (93%), and ophthalmoplegia (90%) with weak extraocular movements, strabismus, and diplopia. Neurotoxicity developed within 8 h post-bite in all patients. No bulbar, respiratory or limb muscle weakness occurred. Neurotoxicity was associated with bites by larger snakes (p < 0.0001) and higher peak serum venom concentrations (p = 0.0025). Antivenom immediately decreased unbound venom in blood. Of 52 patients without neurotoxicity when they received antivenom, 31 developed neurotoxicity. sfEMG in 27 patients with neurotoxicity and 23 without had slightly elevated median jitter on day 1 compared to 29 normal subjects but normalised thereafter. Neurological features resolved in 80% of patients by day 3 with ptosis and weak eye movements resolving last. No clinical or neurophysiological abnormality was detected at 6 weeks or 6 months. Conclusion: Sri Lankan Russells viper envenoming causes mild neuromuscular dysfunction with no long-term effects. Indian polyvalent antivenom effectively binds free venom in blood but does not reverse neurotoxicity.]]> Sat 24 Mar 2018 07:39:43 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:26377 Pethia melanomaculata (Deraniyagala) is available for the Sri Lankan fish previously referred to P. ticto, being distinguished from its Indian congeners by the combination of the following characters; having 1/2 4/1/3 1/2 scales in transverse line on body; body depth 32.4-41.5% of standard length (SL); head length (HL) 26.1-29.2% of SL; snout length 25.3-35.6% of HL; eye diameter 24.4-31.9% of HL; a small black humeral spot on lateral-line scales 3 or 4; a black spot on caudal peduncle, on scales 16-18 of the lateral line series; 3 unbranched dorsal-fin rays, the last one strongly serrated, with 8-11 serrae.]]> Sat 24 Mar 2018 07:33:06 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:27073 4) serum samples were available from 255 Russell's viper (Daboia russelii) envenomed patients. Enzyme-linked immunosorbent assay was used to measure venom, antivenom and venom-antivenom (VAV) complexes. In 79/255 (31%) there was persistent/recurrent venom detected despite antivenom being present. In these post-antivenom samples, VAV was also detected at the same time as venom was detected. Anti-horse (aH) antiserum was bound to UltraLink (UL) resin and added to in vitro venom-antivenom mixtures, and 15 pre- and post-antivenom samples from patients. There was significantly less free venom detected in in vitro venom-antivenom mixtures to which ULaH had been added compared to those without ULaH added. In 9 post-antivenom patient samples the addition of ULaH reduced venom detected by a median of 80% (69%-88%) compared to only 20% in four pre-antivenom samples. This suggests that the detection of persistent/recurrent venom post-antivenom is due to bound and not free venom.]]> Sat 24 Mar 2018 07:25:20 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:50970 Mon 14 Aug 2023 15:19:54 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:28057 Daboia russelii) envenoming is reported to cause myotoxicity and neurotoxicity, which are different to the effects of envenoming by most other populations of Russell’s vipers. This study aimed to investigate evidence of myotoxicity in Russell’s viper envenoming, response to antivenom and the toxins responsible for myotoxicity. Methodology and Findings: Clinical features of myotoxicity were assessed in authenticated Russell’s viper bite patients admitted to a Sri Lankan teaching hospital. Toxins were isolated using high-performance liquid chromatography. In-vitro myotoxicity of the venom and toxins was investigated in chick biventer nerve-muscle preparations. Of 245 enrolled patients, 177 (72.2%) had local myalgia and 173 (70.6%) had local muscle tenderness. Generalized myalgia and muscle tenderness were present in 35 (14.2%) and 29 (11.8%) patients, respectively. Thirty-seven patients had high (>300 U/l) serum creatine kinase (CK) concentrations in samples 24h post-bite (median: 666 U/l; maximum: 1066 U/l). Peak venom and 24h CK concentrations were not associated (Spearman’s correlation; p = 0.48). The 24h CK concentrations differed in patients without myotoxicity (median 58 U/l), compared to those with local (137 U/l) and generalised signs/symptoms of myotoxicity (107 U/l; p = 0.049). Venom caused concentration-dependent inhibition of direct twitches in the chick biventer cervicis nerve-muscle preparation, without completely abolishing direct twitches after 3 h even at 80 μg/ml. Indian polyvalent antivenom did not prevent in-vitro myotoxicity at recommended concentrations. Two phospholipase A2 toxins with molecular weights of 13kDa, U1-viperitoxin-Dr1a (19.2% of venom) and U1-viperitoxin-Dr1b (22.7% of venom), concentration dependently inhibited direct twitches in the chick biventer cervicis nerve-muscle preparation. At 3 μM, U1-viperitoxin-Dr1a abolished twitches, while U1-viperitoxin-Dr1b caused 70% inhibition of twitch force after 3h. Removal of both toxins from whole venom resulted in no in-vitro myotoxicity. Conclusion: The study shows that myotoxicity in Sri Lankan Russell’s viper envenoming is mild and non-life threatening, and due to two PLA2 toxins with weak myotoxic properties.]]> Mon 11 Mar 2019 12:11:05 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:34525 1.4. The diagnostic utility of WBCT20 was determined by calculating the sensitivity and specificity of the WBCT20 on admission for detecting VICC. There were 987 snake bites where both WBCT20 and PT were done on admission samples. This included 79 patients (8 %) with VICC. The WBCT20 was positive in 65/79 patients with VICC (sensitivity 82 %; 95 % confidence interval [CI]: 72-90 %) and was falsely positive in 13/908 with no coagulopathy. The WBCT20 was negative in 895/908 snake bites with no coagulopathy (specificity: 98 % 95 % CI: 97-99 %) and was falsely negative in 14/79 with VICC. Using trained clinical staff, the WBCT20 test had a relatively good sensitivity for the detection of VICC, but still missed almost one fifth of cases where antivenom was potentially indicated.]]> Fri 22 Mar 2019 13:03:57 AEDT ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:28058 Bungarus caeruleus) bites were recruited from a Sri Lankan hospital. All patients had serial neurological examinations and stimulated concentric needle single-fibre electromyography (sfEMG) of orbicularis oculi in hospital at 6 wk and 6-9 mth post-bite. Principal Findings: There were 33 patients enrolled (median age 35 y; 24 males). Eight did not develop neurotoxicity and had normal sfEMG. Eight had mild neurotoxicity with ptosis, normal sfEMG; six received antivenom and all recovered within 20-32 h. Seventeen patients developed severe neurotoxicity with rapidly descending paralysis, from ptosis to complete ophthalmoplegia, facial, bulbar and neck weakness. All 17 received Indian polyvalent antivenom a median 3.5 h post-bite (2.8-7.2 h), which cleared unbound venom from blood. Despite this, the paralysis worsened requiring intubation and ventilation within 7 h post-bite. sfEMG showed markedly increased jitter and neuromuscular blocks within 12 h. sfEMG abnormalities gradually improved over 24 h, corresponding with clinical recovery. Muscle recovery occurred in ascending order. Myotoxicity was not evident, clinically or biochemically, in any of the patients. Patients were extubated a median 96 h post-bite (54-216 h). On discharge, median 8 days (4-12 days) post-bite, patients were clinically normal but had mild sfEMG abnormalities which persisted at 6 wk post-bite. There were no clinical or neurophysiological abnormalities at 6-9 mth. Conclusions: Common krait envenoming causes rapid onset severe neuromuscular paralysis which takes days to recover clinically consistent with sfEMG. Subclinical neuromuscular dysfunction lasts weeks but was not permanent. Antivenom effectively cleared venom but did not prevent worsening or reverse neuromuscular paralysis.]]> Fri 18 Sep 2020 15:19:17 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:18589 Fri 13 Jul 2018 15:49:03 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:22947 Fri 13 Jul 2018 15:45:17 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:17286 Fri 09 Sep 2016 16:17:26 AEST ]]> https://ogma.newcastle.edu.au/vital/access/ /manager/Repository/uon:45713 Fri 04 Nov 2022 10:27:59 AEDT ]]>