Specialist medical toxicologist consultations provided by the New Zealand National Poisons Centre, 2018-2020.

AIMS: The National Poisons Centre (NPC) provides 24/7 specialist medical toxicologist consultations to healthcare professionals regarding the clinical management of poisoning cases. The use of toxicologist services was investigated to characterise the extent and content of consults to inform further development of this service. METHODS: A retrospective analysis of 2018-2020 medical toxicologist consultations summarised contact numbers, professional backgrounds and district health boards (DHBs) of the people contacting the NPC, and the patient(s) and substance(s) involved. RESULTS: There were 3,451 medical toxicologist consultations with 2,400 (67%) provided directly to healthcare professionals. Crude rates of consults increased across all DHBs. Of all 2,603 therapeutic substances that were consulted about during the study period, 1,492 (57.3%) were drugs affecting the nervous system, and paracetamol was the most common individual drug (528; 20.3%). Of all 1,185 non-therapeutic substance exposures that were advised on, 66 (5.6%) were unidentified mushrooms, 51 (4.3%) unidentified substances, and 47 (4.0%) lead exposures. CONCLUSIONS: There was increasing utilisation of the NPC service by healthcare professionals from all 24 areas of the country, covering a wide range of substance exposures and scenarios. The growing utilisation suggests healthcare professionals derive value from this consultation service for the care of their patients.

The bacterial community of childcare centers: potential implications for microbial dispersal and child exposure.

BACKGROUND: Bacterial communities within built environments reflect differences in sources of bacteria, building design, and environmental contexts. These communities impact the health of their occupants in many ways. Children interact with the built environment differently than do adults as a result of their unique behaviors, size, and developmental status. Consequently, understanding the broader bacterial community to which children are exposed will help inform public health efforts and contribute to our growing understanding of the bacterial community associated with childcare centers. METHODS: We sampled childcare centers to survey the variation in bacterial community composition across five surfaces found inside and outside twelve classrooms and six centers using 16S rRNA marker gene amplicon sequencing. We then correlated these bacterial community analyses of surfaces with environmental and demographic measures of illumination and classroom occupant density. RESULTS: The childcare environment was dominated by human-associated bacteria with modest input from outdoor sources. Though the bacterial communities of individual childcare centers differed, there was a greater difference in the bacterial community within a classroom than among centers. Surface habitats-fomites-within the classroom, did not differ in community composition despite differing proximity to likely sources of bacteria, and possible environmental filters, such as light. Bacterial communities did correlate with occupant density and differed significantly between high and low usage surfaces. CONCLUSIONS: Our results suggest built environments inhabited by young children are similar to functionally equivalent built environments inhabited by adults, despite the different way young children engage with their environment. Ultimately, these results will be useful when further interrogating microbial dispersal and human exposure to microorganisms in built environments that specifically cater to young children.

Predictors of developmental surveillance completion at six months of age in south western Sydney.

BACKGROUND: While developmental surveillance programs promote early identification of child developmental problems, evidence has indicated suboptimal uptake. This study aimed to identify predictors of developmental surveillance completion at 6 months postpartum. METHODS: Questionnaires were administered to the parents of 510 infants who were born in south western Sydney, Australia over a 22-month period. Attendance for developmental screening and completion of the Parents' Evaluation of Developmental Status (PEDS) at 6 months postpartum were modelled separately using multivariable logistic regression. RESULTS: Developmental surveillance attendance was predicted by higher levels of maternal education, annual income and being informed about checks. PEDS completion at 6 months of age was predicted by higher income and being informed, as well as being married, employed, speaking English at home, full-term birth and the professional status of the practitioner completing the check. CONCLUSIONS: Barriers to developmental surveillance included low socioeconomic status, linguistic diversity and possible gaps in parental knowledge and professional education. Developmental surveillance rates may be increased by the addition of targeted parental and professional support within current universal frameworks.

Characterisation of the epithermal neutron irradiation facility at the Portuguese research reactor using MCNP.

The radiation field at the epithermal beamline and irradiation chamber installed at the Portuguese Research Reactor (RPI) at the Campus Tecnológico e Nuclear of Instituto Superior Técnico was characterised in the context of Prompt Gamma Neutron Activation Analysis (PGNAA) applications. Radiographic films, activation foils and thermoluminescence dosimeters were used to measure the neutron fluence and photon dose rates in the irradiation chamber. A fixed-source MCNPX model of the beamline and chamber was developed and compared to measurements in the first step towards planning a new irradiation chamber. The high photon background from the reactor results in the saturation of the detector and the current facility configuration yields an intrinsic insensitivity to various elements of interest for PGNAA. These will be addressed in future developments.

Isopropanol poisoning.

INTRODUCTION: Isopropanol is a clear, colorless liquid with a fruity odor and a mild bitter taste. Most commonly found domestically as rubbing alcohol, isopropanol is also found in numerous household and commercial products including cleaners, disinfectants, antifreezes, cosmetics, solvents, inks, and pharmaceuticals. AIM: The aim of this review is to critically review the epidemiology, toxicokinetics, mechanisms of toxicity, clinical features, diagnosis, and management of isopropanol poisoning. METHODS: OVID MEDLINE and ISI Web of Science were searched to November 2013 using the words "isopropanol", "isopropyl alcohol", "2-propanol", "propan-2-ol", and "rubbing alcohol" combined with the keywords "poisoning", "poison", "toxicity", "ingestion", "adverse effects", "overdose", or "intoxication". These searches identified 232 citations, which were then screened via their abstract to identify relevant articles referring specifically to the epidemiology, toxicokinetics, mechanisms of toxicity, clinical features, diagnosis, and management of isopropanol poisoning; 102 were relevant. Further information was obtained from book chapters, relevant news reports, and internet resources. These additional searches produced eight non-duplicate relevant citations. EPIDEMIOLOGY: The majority of isopropanol exposures are unintentional and occur in children less than 6 years of age. Although isopropanol poisoning appears to be a reasonably common occurrence, deaths are rare. TOXICOKINETICS: Isopropanol is rapidly absorbed following ingestion with peak plasma concentrations occurring within 30 min. It can also be absorbed following inhalation or dermal exposure. Isopropanol is widely distributed with a volume of distribution of 0.45-0.55 L/kg. Isopropanol is metabolized by alcohol dehydrogenase to acetone, acetol and methylglyoxal, propylene glycol, acetate, and formate with conversion of these metabolites to glucose and other products of intermediary metabolism. The elimination of isopropanol is predominantly renal, though some pulmonary excretion of isopropanol and acetone occurs. In one case 20% of the absorbed dose was eliminated unchanged in urine, with the remainder excreted as acetone and metabolites of acetone. The elimination half-life of isopropanol is between 2.5 and 8.0 h, whereas elimination of acetone is slower with a half-life following isopropanol ingestion of between 7.7 and 27 h. MECHANISMS OF TOXICITY: While the exact mechanism of action of isopropanol has not been fully elucidated, brain stem depression is thought to be the predominant mechanism. While the clinical effects are thought to be mostly due to isopropanol, acetone may also contribute. CLINICAL FEATURES: The major features of severe poisoning are due to CNS and respiratory depression, shock, and circulatory collapse. The most common metabolic effects are an increased osmol (osmolal) gap, ketonemia, and ketonuria. Diagnosis. Poisoning can be diagnosed using the measurement of isopropanol serum concentrations, though these may not be readily available. Diagnosis is therefore more typically made on the basis of the patient's history and clinical presentation. An osmol gap, ketonemia, and/or ketonuria without metabolic acidosis, along with a fruity or sweet odor on the breath and CNS depression support the diagnosis. Management. Supportive care is the mainstay of management with primary emphasis on respiratory and cardiovascular support. Hemodialysis enhances elimination of isopropanol and acetone and should be considered in very severe poisoning. CONCLUSIONS: Severe isopropanol poisoning results in CNS and respiratory depression and circulatory collapse. Treatment primarily consists of symptom-directed supportive care. Although hemodialysis increases the elimination of isopropanol and acetone substantially, it should only be considered in severe life-threatening poisonings. Patients usually make a full recovery provided they receive prompt supportive care.

Full recovery from a potentially lethal dose of mercuric chloride.

INTRODUCTION: Mercuric chloride poisoning is rare yet potentially life-threatening. We report a case of poisoning with a potentially significant amount of mercuric chloride which responded to aggressive management. CASE REPORT: A 19-year-old female presented to the Emergency Department with nausea, abdominal discomfort, vomiting of blood-stained fluid, and diarrhea following suicidal ingestion of 2-4 g of mercuric chloride powder. An abdominal radiograph showed radio-opaque material within the gastric antrum and the patient's initial blood mercury concentration was 17.9 µmol/L (or 3.58 mg/L) at 3 h post-ingestion. Given the potential toxicity of inorganic mercury, the patient was admitted to the intensive care unit and chelation with dimercaprol was undertaken. Further clinical effects included mild hemodynamic instability, acidosis, hypokalemia, leukocytosis, and fever. The patient's symptoms began to improve 48 h after admission and resolved fully within a week. DISCUSSION: Mercuric chloride has an estimated human fatal dose of between 1 and 4 g. Despite a reported ingestion of a potentially lethal dose and a high blood concentration, this patient experienced mild to moderate poisoning only and she responded to early and appropriate intervention. Mercuric chloride can produce a range of toxic effects including corrosive injury, severe gastrointestinal disturbances, acute renal failure, circulatory collapse, and eventual death. Treatment includes close observation and aggressive supportive care along with chelation, preferably with 2,3-dimercapto-1-propane sulfonate or 2,3-meso-dimercaptosuccinic acid.

Effects of parental radiation exposure on developmental instability in grasshoppers.

Mutagenic and epigenetic effects of environmental stressors and their transgenerational consequences are of interest to evolutionary biologists because they can amplify natural genetic variation. We studied the effect of parental exposure to radioactive contamination on offspring development in lesser marsh grasshopper Chorthippus albomarginatus. We used a geometric morphometric approach to measure fluctuating asymmetry (FA), wing shape and wing size. We measured time to sexual maturity to check whether parental exposure to radiation influenced offspring developmental trajectory and tested effects of radiation on hatching success and parental fecundity. Wings were larger in early maturing individuals born to parents from high radiation sites compared to early maturing individuals from low radiation sites. As time to sexual maturity increased, wing size decreased but more sharply in individuals from high radiation sites. Radiation exposure did not significantly affect FA or shape in wings nor did it significantly affect hatching success and fecundity. Overall, parental radiation exposure can adversely affect offspring development and fitness depending on developmental trajectories although the cause of this effect remains unclear. We suggest more direct measures of fitness and the inclusion of replication in future studies to help further our understanding of the relationship between developmental instability, fitness and environmental stress.

Poisonous plants in New Zealand: a review of those that are most commonly enquired about to the National Poisons Centre.

INTRODUCTION: New Zealand has a number of plants, both native and introduced, contact with which can lead to poisoning. The New Zealand National Poisons Centre (NZNPC) frequently receives enquiries regarding exposures to poisonous plants. Poisonous plants can cause harm following inadvertent ingestion, via skin contact, eye exposures or inhalation of sawdust or smoked plant matter. AIM: The purpose of this article is to determine the 15 most common poisonous plant enquiries to the NZNPC and provide a review of current literature, discussing the symptoms that might arise upon exposure to these poisonous plants and the recommended medical management of such poisonings. METHODS: Call data from the NZNPC telephone collection databases regarding human plant exposures between 2003 and 2010 were analysed retrospectively. The most common plants causing human poisoning were selected as the basis for this review. An extensive literature review was also performed by systematically searching OVID MEDLINE, ISI Web of Science, Scopus and Google Scholar. Further information was obtained from book chapters, relevant news reports and web material. RESULTS: For the years 2003-2010 inclusive, a total of 256,969 enquiries were received by the NZNPC. Of these enquiries, 11,049 involved exposures to plants and fungi. The most common poisonous plant enquiries, in decreasing order of frequency, were: black nightshade (Solanum nigrum), arum lily (Zantedeschia aethiopica), kowhai (Sophora spp.), euphorbia (Euphorbia spp.), peace lily (Spathiphyllum spp.), agapanthus (Agapanthus spp.), stinking iris (Iris foetidissima), rhubarb (Rheum rhabarbarum), taro (Colocasia esculentum), oleander (Nerium oleander), daffodil (Narcissus spp.), hemlock (Conium maculatum), karaka (Corynocarpus laevigatus), foxglove (Digitalis purpurea) and ongaonga/New Zealand tree nettle (Urtica ferox). The combined total of enquiries for these 15 species was 2754 calls (representing approximately 25% of all enquiries regarding plant exposures). The signs and symptoms resulting from poisoning from these plants are discussed. Medical treatment recommendations are made. CONCLUSION: Poisoning following ingestion or other forms of exposures to plants in New Zealand is relatively common, particularly among children. However, serious adverse reactions are comparatively rare. Accurate plant identification and details on the type of exposure can be important in assessing the likely risks. Effective medical management of these poisonings can be achieved by following the principles outlined in this review.

The clinical toxicology of the designer "party pills" benzylpiperazine and trifluoromethylphenylpiperazine.

INTRODUCTION: Benzylpiperazine (BZP) and trifluoromethylphenylpiperazine (TFMPP) are synthetic phenylpiperazine analogues. BZP was investigated as a potential antidepressant in the early 1970s but was found unsuitable for this purpose. More recently, BZP and TFMPP have been used as substitutes for amfetamine-derived designer drugs. They were legally available in a number of countries, particularly in New Zealand, and were marketed as party pills, but are now more heavily regulated. This article will review the mechanisms of toxicity, toxicokinetics, clinical features, diagnosis, and management of poisoning due to BZP and TFMPP. METHODS: OVID MEDLINE and ISI Web of Science were searched systematically for studies on BZP and TFMPP and the bibliographies of identified articles were screened for additional relevant studies including nonindexed reports. Nonpeer-reviewed sources were also accessed. In all, 179 papers excluding duplicates were identified and 74 were considered relevant. MECHANISMS OF ACTION: BZP and TFMPP have stimulant and amfetamine-like properties. They enhance the release of catecholamines, particularly of dopamine, from sympathetic nerve terminals, increasing intra-synaptic concentrations. The resulting elevated intra-synaptic monoamine concentrations cause increased activation of both central and peripheral α- and ß-adrenergic postsynaptic receptors. BZP has primarily dopaminergic and noradrenergic action while TFMPP has a more direct serotonin agonist activity. TOXICOKINETICS: There is limited information on the kinetics of these drugs. Following ingestion, peak plasma concentrations are reached after 60 to 90 min. Both drugs would be expected to cross the blood brain barrier and they are metabolized mainly by hydroxylation and N-dealkylation catalyzed by cytochrome P450 and catechol-o-methyl transferase enzymes. In humans, only small amounts of both BZP and TFMPP are excreted in the urine, suggesting a low bioavailability. The serum half-lives of BZP and TFMPP are relatively short with elimination being essentially complete in 44 h for BZP and 24 h for TFMPP. CLINICAL FEATURES: These compounds can cause harmful effects when taken recreationally. Commonly reported features include palpitations, agitation, anxiety, confusion, dizziness, headache, tremor, mydriasis, insomnia, urine retention, and vomiting. Seizures are induced in some patients even at low doses. Severe multiorgan toxicity has been reported, though fatalities have not been recorded conclusively. MANAGEMENT: Supportive care including the termination of seizures is paramount, with relief of symptoms usually being provided by benzodiazepines alone. CONCLUSIONS: BZP and TFMP can cause sympathomimetic effects in the intoxicated patient. Appropriate, symptom-directed supportive care should ensure a good recovery.

The clinical toxicology of metamfetamine.

INTRODUCTION: Metamfetamine is a highly addictive amfetamine analog that acts primarily as a central nervous system (CNS) stimulant. The escalating abuse of this drug in recent years has lead to an increasing burden upon health care providers. An understanding of the drug's toxic effects and their medical treatment is therefore essential for the successful management of patients suffering this form of intoxication. AIM: The aim of this review is to summarize all main aspects of metamfetamine poisoning including epidemiology, mechanisms of toxicity, toxicokinetics, clinical features, diagnosis, and management. METHODS: A summary of the literature on metamfetamine was compiled by systematically searching OVID MEDLINE and ISI Web of Science. Further information was obtained from book chapters, relevant news reports, and web material. Epidemiology. Following its use in the Second World War, metamfetamine gained popularity as an illicit drug in Japan and later the United States. Its manufacture and use has now spread to include East and South-East Asia, North America, Mexico, and Australasia, and its world-wide usage, when combined with amfetamine, exceeds that of all other drugs of abuse except cannabis. Mechanisms of toxicity. Metamfetamine acts principally by stimulating the enhanced release of catecholamines from sympathetic nerve terminals, particularly of dopamine in the mesolimbic, mesocortical, and nigrostriatal pathways. The consequent elevation of intra-synaptic monoamines results in an increased activation of central and peripheral α±- and ß-adrenergic postsynaptic receptors. This can cause detrimental neuropsychological, cardiovascular, and other systemic effects, and, following long-term abuse, neuronal apoptosis and nerve terminal degeneration. Toxicokinetics. Metamfetamine is rapidly absorbed and well distributed throughout the body, with extensive distribution across high lipid content tissues such as the blood-brain barrier. In humans the major metabolic pathways are aromatic hydroxylation producing 4-hydroxymetamfetamine and N-demethylation to form amfetamine. Metamfetamine is excreted predominantly in the urine and to a lesser extent by sweating and fecal excretion, with reported terminal half-lives ranging from ∼5 to 30 h. Clinical features. The clinical effects of metamfetamine poisoning can vary widely, depending on dose, route, duration, and frequency of use. They are predominantly characteristic of an acute sympathomimetic toxidrome. Common features reported include tachycardia, hypertension, chest pain, various cardiac dysrhythmias, vasculitis, headache, cerebral hemorrhage, hyperthermia, tachypnea, and violent and aggressive behaviour. Management. Emergency stabilization of vital functions and supportive care is essential. Benzodiazepines alone may adequately relieve agitation, hypertension, tachycardia, psychosis, and seizure, though other specific therapies can also be required for sympathomimetic effects and their associated complications. CONCLUSION: Metamfetamine may cause severe sympathomimetic effects in the intoxicated patient. However, with appropriate, symptom-directed supportive care, patients can be expected to make a full recovery.

Nicotinic plant poisoning.

INTRODUCTION: A wide range of plants contain nicotinic and nicotinic-like alkaloids. Of this diverse group, those that have been reported to cause human poisoning appear to have similar mechanisms of toxicity and presenting patients therefore have comparable toxidromes. This review describes the taxonomy and principal alkaloids of plants that contain nicotinic and nicotinic-like alkaloids, with particular focus on those that are toxic to humans. The toxicokinetics and mechanisms of toxicity of these alkaloids are reviewed and the clinical features and management of poisoning due to these plants are described. METHODS: This review was compiled by systematically searching OVID MEDLINE and ISI Web of Science. This identified 9,456 papers, excluding duplicates, all of which were screened. Reviewed plants and their principal alkaloids. Plants containing nicotine and nicotine-like alkaloids that have been reported to be poisonous to humans include Conium maculatum, Nicotiana glauca and Nicotiana tabacum, Laburnum anagyroides, and Caulophyllum thalictroides. They contain the toxic alkaloids nicotine, anabasine, cytisine, n-methylcytisine, coniine, n-methylconiine, and gamma-coniceine. MECHANISMS OF TOXICITY: These alkaloids act agonistically at nicotinic-type acetylcholine (cholinergic) receptors (nAChRs). The nicotinic-type acetylcholine receptor can vary both in its subunit composition and in its distribution within the body (the central and autonomic nervous systems, the neuromuscular junctions, and the adrenal medulla). Agonistic interaction at these variable sites may explain why the alkaloids have diverse effects depending on the administered dose and duration of exposure. TOXICOKINETICS: Nicotine and nicotine-like alkaloids are absorbed readily across all routes of exposure and are rapidly and widely distributed, readily traversing the blood-brain barrier and the placenta, and are freely distributed in breast milk. Metabolism occurs predominantly in the liver followed by rapid renal elimination. CLINICAL FEATURES: Following acute exposure, symptoms typically follow a biphasic pattern. The early phase consists of nicotinic cholinergic stimulation resulting in symptoms such as abdominal pain, hypertension, tachycardia, and tremors. The second inhibitory phase is delayed and often heralded by hypotension, bradycardia, and dyspnea, finally leading to coma and respiratory failure. MANAGEMENT: Supportive care is the mainstay of management with primary emphasis on cardiovascular and respiratory support to ensure recovery. CONCLUSIONS: Exposure to plants containing nicotine and nicotine-like alkaloids can lead to severe poisoning but, with prompt supportive care, patients should make a full recovery.

Diethylene glycol poisoning.

INTRODUCTION: Diethylene glycol (DEG) is a clear, colorless, practically odorless, viscous, hygroscopic liquid with a sweetish taste. In addition to its use in a wide range of industrial products, it has also been involved in a number of prominent mass poisonings spanning back to 1937. Despite DEG's toxicity and associated epidemics of fatal poisonings, a comprehensive review has not been published. METHODS: A summary of the literature on DEG was compiled by systematically searching OVID MEDLINE and ISI Web of Science. Further information was obtained from book chapters, relevant news reports, and web material. AIM: The aim of this review is to summarize all main aspects of DEG poisoning including epidemiology, toxicokinetics, mechanisms of toxicity, clinical features, toxicity of DEG, diagnosis, and management. EPIDEMIOLOGY: Most of the documented cases of DEG poisoning have been epidemics (numbering over a dozen) where DEG was substituted in pharmaceutical preparations. More often, these epidemics have occurred in developing and impoverished nations where there is limited access to intensive medical care and quality control procedures are substandard. TOXICOKINETICS: Following ingestion, DEG is rapidly absorbed and distributed within the body, predominantly to regions that are well perfused. Metabolism occurs principally in the liver and both the parent and the metabolite, 2-hydroxyethoxyacetic acid (HEAA), are renally eliminated rapidly. MECHANISMS OF TOXICITY: Although the mechanism of toxicity is not clearly elucidated, research suggests that the DEG metabolite, HEAA, is the major contributor to renal and neurological toxicities. CLINICAL FEATURES: The clinical effects of DEG poisoning can be divided into three stages: The first phase consists of gastrointestinal symptoms with evidence of inebriation and developing metabolic acidosis. If poisoning is pronounced, patients can progress to a second phase with more severe metabolic acidosis and evidence of emerging renal injury, which, in the absence of appropriate supportive care, can lead to death. If patients are stabilized, they may then enter the final phase with various delayed neuropathies and other neurological effects, sometimes fatal. TOXICITY OF DEG: Doses of DEG necessary to cause human morbidity and mortality are not well established. They are based predominantly on reports following some epidemics of mass poisonings, which may underestimate toxicity. The mean estimated fatal dose in an adult has been defined as approximately 1 mL/kg of pure DEG. MANAGEMENT: Initial treatment consists of appropriate airway management and attention to acid-base abnormalities. Prompt use of fomepizole or ethanol is important in preventing the formation of the toxic metabolite HEAA; hemodialysis can also be critical, and assisted ventilation may be required. CONCLUSIONS: DEG ingestion can lead to serious complications that may prove fatal. Prognosis may be improved, however, with prompt supportive care and timely use of fomepizole or ethanol.

Poisoning due to water hemlock.

INTRODUCTION: Water hemlock, which encompasses a range of species divided across two genera (Cicuta and Oenanthe), are regarded as being among the most poisonous plants both in North America and in the United Kingdom. Despite their toxicity, the literature consists almost entirely of case reports. AIM: The aim of this review is to summarize this literature by covering all aspects of taxonomy and botanical characterization, principal toxins, basic pharmacology including mechanisms of toxicity, and the clinical features, diagnosis, and management of poisoning. MECHANISMS OF TOXICITY: The principal toxins, cicutoxin and oenanthotoxin, belong to a group of C17 conjugated polyacetylenes. They act as (noncompetitive) gamma-aminobutyric acid antagonists in the central nervous system (CNS), resulting in unabated neuronal depolarization that can lead to seizures. Ingestion of even a small amount of plant matter may result in severe intoxication. FEATURES: After ingestion, the patient is most likely to experience CNS stimulatory effects including seizures that, in the absence of aggressive supportive care, can result in death. Other features include nausea, vomiting, diarrhea, tachycardia, mydriasis, rhabdomyolysis, renal failure, coma, respiratory impairment, and cardiac dysrhythmias. MANAGEMENT: Treatment consists mainly of prompt airway management and seizure control, plus decontamination if achieved early and after stabilization. In the event of renal failure, the use of hemodialysis has been employed successfully. CONCLUSIONS: The ingestion of water hemlock can lead to serious complications that may be fatal. Prognosis is good, however, if prompt supportive care is provided.

New Zealand's venomous creatures.

AIM: New Zealand is home to a small number of venomous creatures. The purpose of this review is to educate and update healthcare professionals on the management of envenoming from these creatures. METHODS: An extensive literature review was performed by systematically searching OVID MEDLINE and ISI Web of Science. In addition, further information was obtained from book chapters, relevant news reports, and web material. RESULTS: The signs and symptoms resulting from envenoming of clinically significant venomous creatures found in New Zealand are discussed. Definitive medical treatment recommendations are made. CONCLUSION: Encounters with New Zealand's few venomous creatures, while rarely fatal, can cause significant morbidity. Effective management can be achieved by informed health professionals having regard to the principles outlined in this review.

Molecular determinants of virulence of West Nile virus in North America.

West Nile virus (WNV) is a mosquito-borne flavivirus that until very recently had not been found in the Americas. In 1999, there was an outbreak of West Nile encephalitis in New York and surrounding areas, involving 62 human cases, including 7 fatalities. The virus has subsequently become established in the United States of America (U.S.) with 4156 human cases, including 284 deaths, in 2002. The WNV strains found in the U.S. are members of "lineage I", a genetic grouping that includes viruses from Europe, Asia and Africa. Molecular epidemiologic studies indicate that two genetic variants of WNV emerged in 2002. The major genetic variant is found in most parts of the U.S., while the minor genetic variant has been identified only on the southeast coast of Texas. Investigation of WNV in mouse and hamster models demonstrated that strains from the U.S. are highly neurovirulent and neuroinvasive in these laboratory rodents. Other strains, such as Ethiopia 76a from lineage I, are not neuroinvasive and represent important viruses which can be used to elucidate the molecular basis of virulence and attenuation of WNV. To identify putative molecular determinants of virulence and attenuation, we have undertaken comparative nucleotide sequencing of Ethiopia 76a and strains from the U.S. The results show that the two viruses differ by 5 amino acids in the envelope (E) protein, including loss of the glycosylation site. Comparison of our panel of 27 WNV strains suggests that E protein glycosylation is a major determinant of the mouse neuroinvasive phenotype.

Nucleotide sequencing and serological evidence that the recently recognized deer tick virus is a genotype of Powassan virus.

Deer tick virus (DTV) is a recently recognized North American virus isolated from Ixodes dammini ticks. Nucleotide sequencing of fragments of structural and non-structural protein genes suggested that this virus was most closely related to the tick-borne flavivirus Powassan (POW), which causes potentially fatal encephalitis in humans. To determine whether DTV represents a new and distinct member of the Flavivirus genus of the family Flaviviridae, we sequenced the structural protein genes and 5' and 3' non-coding regions of this virus. In addition, we compared the reactivity of DTV and POW in hemagglutination inhibition tests with a panel of polyclonal and monoclonal antisera, and performed cross-neutralization experiments using anti-DTV antisera. Nucleotide sequencing revealed a high degree of homology between DTV and POW at both nucleotide (>80% homology) and amino acid (>90% homology) levels, and the two viruses were indistinguishable in serological assays and mouse neuroinvasiveness. On the basis of these results, we suggest that DTV should be classified as a genotype of POW virus.

Chlamydia pneumoniae and chlamydial heat shock protein 60 stimulate proliferation of human vascular smooth muscle cells via toll-like receptor 4 and p44/p42 mitogen-activated protein kinase activation.

An early component of atherogenesis is abnormal vascular smooth muscle cell (VSMC) proliferation. The presence of Chlamydia pneumoniae in many atherosclerotic lesions raises the possibility that this organism plays a causal role in atherogenesis. In this study, C pneumoniae elementary bodies (EBs) rapidly activated p44/p42 mitogen-activated protein kinases (MAPKs) and stimulated proliferation of VSMCs in vitro. Exposure of VSMCs derived from human saphenous vein to C pneumoniae EBs (3x10(7) inclusion forming units/mL) enhanced bromodeoxyuridine (BrdU) incorporation 12+/-3-fold. UV- and heat-inactivated C pneumoniae EBs also stimulated VSMC proliferation, indicating a role of direct stimulation by chlamydial antigens. However, the mitogenic activity of C pneumoniae was heat-labile, thus excluding a role of lipopolysaccharide. Chlamydial hsp60 (25 microg/mL) replicated the effect of C pneumoniae, stimulating BrdU incorporation 7+/-3-fold. Exposure to C pneumoniae or chlamydial hsp60 rapidly activated p44/p42 MAPK, within 5 to 10 minutes of exposure. In addition, PD98059 and U0126, which are two distinct inhibitors of upstream MAPK kinase 1/2 (MEK1/2), abolished the mitogenic effect of C pneumoniae and chlamydial hsp60. Toll-like receptors (TLRs) act as sensors for microbial antigens and can signal via the p44/p42 MAPK pathway. Human VSMCs were shown to express TLR4 mRNA and protein, and a TLR4 antagonist abolished chlamydial hsp60-induced VSMC proliferation and attenuated C pneumoniae-induced MAPK activation and VSMC proliferation. Together these results indicate that C pneumoniae and chlamydial hsp60 are potent inducers of human VSMC proliferation and that these effects are mediated, at least in part, by rapid TLR4-mediated activation of p44/p42 MAPK.