Medical Journal of Australia

ABSTRACT Objective: Fatal snakebites at Port Moresby General Hospital (PMGH), Papua New Guinea (PNG), were examined to identify interventions that may improve patient survival. Design: Retrospective case series. Subjects and setting: Inpatients at PMGH who presented with snakebite, had evidence of envenomation, and died as inpatients between 1 January 1992 and 31 December 2001. Outcome measures: Number and cause of fatalities; ventilation bed-days; antivenom timing, dose and price. Results: 87 deaths occurred among 722 snakebite admissions to the intensive care unit (ICU). Of these 722 patients, 82.5% were ventilated, representing 45% of all ventilated ICU patients and 60% (3430/5717) of all ICU ventilator bed-days. The median duration of ventilation in fatal snakebite cases was significantly less than in non-fatal cases for children (3.0 v. 4.5 days) and adults (3.0 v. 5.0 days). The case-fatality rate for children (14.6%) was significantly greater than that for adults (8.2%). Sixty fatalities were examined in detail: 75% received blood products; 53% received antivenom (mostly a single ampoule of polyvalent), but only 5% received antivenom р 4 hours post-bite. Major causes of death included respiratory complications (50%), probable intracerebral haemorrhage (17%), and renal failure (10%). Antivenom unit costs increased significantly over the decade; in 2000 an ampoule of polyvalent antivenom was 40-fold more expensive in PNG than in Australia on a gross domestic product (A$) per capita basis. Conclusions: Management of severe snakebite is a major challenge for PMGH. Improved antivenom procurement and use policies (including increased use of appropriate monovalent antivenoms), combined with targeted snakebite education interventions (community-and hospital-based), are key interventions to reduce the MJA 2004; 181: 687-691 ongoing toll from snakebite

Snakebite mortality at Port Moresby General Hospital, Papua New Guinea, 1992–2001

Objective: Fatal snakebites at Port Moresby General Hospital (PMGH), Papua New Guinea (PNG), were examined to identify interventions that may improve patient survival.\ud \ud Design: Retrospective case series.\ud \ud Subjects and setting: Inpatients at PMGH who presented with snakebite, had evidence of envenomation, and died as inpatients between 1 January 1992 and 31 December 2001.\ud \ud Outcome measures: Number and cause of fatalities; ventilation bed-days; antivenom timing, dose and price.\ud \ud Results: 87 deaths occurred among 722 snakebite admissions to the intensive care unit (ICU). Of these 722 patients, 82.5% were ventilated, representing 45% of all ventilated ICU patients and 60% (3430/5717) of all ICU ventilator bed-days. The median duration of ventilation in fatal snakebite cases was significantly less than in non-fatal cases for children (3.0 v. 4.5 days) and adults (3.0 v. 5.0 days). The case-fatality rate for children (14.6%) was significantly greater than that for adults (8.2%). Sixty fatalities were examined in detail: 75% received blood products; 53% received antivenom (mostly a single ampoule of polyvalent), but only 5% received antivenom ≤ 4 hours post-bite. Major causes of death included respiratory complications (50%), probable intracerebral haemorrhage (17%), and renal failure (10%). Antivenom unit costs increased significantly over the decade; in 2000 an ampoule of polyvalent antivenom was 40-fold more expensive in PNG than in Australia on a gross domestic product (A$) per capita basis.\ud \ud Conclusions: Management of severe snakebite is a major challenge for PMGH. Improved antivenom procurement and use policies (including increased use of appropriate monovalent antivenoms), combined with targeted snakebite education interventions (community- and hospital-based), are key interventions to reduce the ongoing toll from snakebite

Mesenchymal stem cells promote mesenteric vasodilation through hydrogen sulfide and endothelial nitric oxide

Mesenteric ischemia is a devastating process that can result in intestinal necrosis. Mesenchymal stem cells (MSCs) are becoming a promising treatment modality. We hypothesized that 1) MSCs would promote vasodilation of mesenteric arterioles, 2) hydrogen sulfide (H2S) would be a critical paracrine factor of stem cell-mediated vasodilation, 3) mesenteric vasodilation would be impaired in the absence of endothelial nitric oxide synthase (eNOS) within the host tissue, and 4) MSCs would improve the resistin-to-adiponectin ratio in mesenteric vessels. H2S was measured with a specific fluorophore (7-azido-3-methylcoumarin) in intact MSCs and in cells with the H2S-producing enzyme cystathionine β synthase (CBS) knocked down with siRNA. Mechanical responses of isolated second- and third-order mesenteric arteries (MAs) from wild-type and eNOS knockout (eNOSKO) mice were monitored with pressure myography, after which the vessels were snap frozen and later analyzed for resistin and adiponectin via multiplex beaded assay. Addition of MSCs to the myograph bath significantly increased vasodilation of norepinephrine-precontracted MAs. Knockdown of CBS in MSCs decreased H2S production by MSCs and also decreased MSC-initiated MA dilation. MSC-initiated vasodilation was further reduced in eNOSKO vessels. The MA resistin-to-adiponectin ratio was higher in eNOSKO vessels compared with wild-type. These results show that MSC treatment promotes dilation of MAs by an H2S-dependent mechanism. Furthermore, functional eNOS within the host mesenteric bed appears to be essential for maximum stem cell therapeutic benefit, which may be attributable, in part, to modifications in the resistin-to-adiponectin ratio. NEW & NOTEWORTHY Stem cells have been shown to improve survival, mesenteric perfusion, and histological injury scores following intestinal ischemia. These benefits may be due to the paracrine release of hydrogen sulfide. In an ex vivo pressure myography model, we observed that mesenteric arterial dilation improved with stem cell treatment. Hydrogen sulfide release from stem cells and endothelial nitric oxide synthase within the vessels were critical components of optimizing stem cell-mediated mesenteric artery dilation

Phospholipase A2 in Cnidaria

Phospholipase A2 (PLA2) is an enzyme present in snake and other venoms and body fluids. We measured PLA2 catalytic activity in tissue homogenates of 22 species representing the classes Anthozoa, Hydrozoa, Scyphozoa and Cubozoa of the phylum Cnidaria. High PLA2 levels were found in the hydrozoan fire coral Millepora sp. (median 735 U/g protein) and the stony coral Pocillopora damicornis (693 U/g) that cause skin irritation upon contact. High levels of PLA2 activity were also found in the acontia of the sea anemone Adamsia carciniopados (293 U/g). Acontia are long threads containing nematocysts and are used in defense and aggression by the animal. Tentacles of scyphozoan and cubozoan species had high PLA2 activity levels: those of the multitentacled box jellyfish Chironex fleckeri contained 184 U/g PLA2 activity. The functions of cnidarian PLA2 may include roles in the capture and digestion of prey and defense of the animal. The current observations support the idea that cnidarian PLA2 may participate in the sting site irritation and systemic envenomation syndrome resulting from contact with cnidarians