Sea lice levels on wild Atlantic salmon, Salmo salar L., returning to the coast of Ireland.

The sea lice population structure, prevalence and intensity of Lepeophtheirus salmonis have been studied over a period extending from 2004 to 2011. Infestation data were collected from the interceptor drift net fishery from 2004 until it was closed in 2006. From 2010, data were collected from the inshore draft net fishery. In all, 34 samples from the drift and draft net fisheries have been analysed to date. Prevalence of infestation with L. salmonis regularly approached 100% in samples of hosts recovered from the offshore drift net fishery. Abundance was variable both within and between years with a maximum mean abundance of 25.8 lice per fish recorded in 2004. The population structure of L. salmonis on hosts recovered in the inshore and estuarine draft net fisheries was different from that observed in the more offshore drift net samples. There is clear evidence of recent infestation with L. salmonis in the draft net samples.

Impact of Lepeophtheirus salmonis infestations on migrating Atlantic salmon , Salmo salar L., smolts at eight locations in Ireland with an analysis of lice-induced marine mortality.

Sea lice infestation as a source of marine mortality of outwardly migrating Atlantic salmon smolts has been investigated by treating groups of ranched salmon, prior to release, with a prophylactic sea lice treatment conferring protection from sea lice infestation. A number of studies have been carried out in Ireland using both established ranched populations and groups of hatchery reared fish imprinted for 5-8 weeks in the sites of experimental releases. In this study, data on 352 142 migrating salmon from twenty-eight releases, at eight locations along Ireland's South and West coasts covering a 9-year period (2001 to 2009) are reviewed. Both published and new data are presented including a previously unpublished time series. The results of a meta-analysis of the combined data suggest that while sea lice-induced mortality on outwardly migrating smolts can be significant, it is a minor and irregular component of marine mortality in the stocks studied and is unlikely to be a significant factor influencing conservation status of salmon stocks.

Rationalizing blood transfusion in cardiac surgery: the impact of a red cell volume-based guideline on blood usage and clinical outcome.

BACKGROUND AND OBJECTIVES: Cardiac surgery is currently considered one of the heaviest users of red blood cells. An explanation may be found, in part, in considering the effect of the heavy clear fluid load associated with cardiopulmonary bypass. This may result in the artificial depression of haemoglobin concentration, overestimating the requirement for red cell transfusion if this is the sole parameter considered. To address this issue, we examined the impact of a red cell volume-based transfusion guideline on transfusion requirement. MATERIALS AND METHODS: This was a single-centre, randomized controlled trial. The cohort of 86 patients was allocated to receive red cells as per the red cell volume guideline (group RCV) or standard haemoglobin concentration-based departmental policy (group C). Outcome measures were red cell transfusion and clinical outcome. RESULTS: All preoperative data were comparable between the two groups. A significantly fewer percentage of patients in group RCV were transfused red cells (RCV = 32.6% vs. C = 53.5%, P = 0.05). No significant difference was found between any of the outcome measures with the exception of median hospital stay (RCV = 5.9 days vs. C = 6.8 days, P = 0.02). CONCLUSION: In elective cardiac surgery patients, considering haemoglobin concentration alone may overestimate the requirement for red cell transfusion. More research is required to determine the impact of restrictive transfusion policies on clinical outcome following cardiac surgery.

Symptom management in patients with established renal failure managed without dialysis.

Increasing numbers of patients with chronic kidney disease Stage 5 (GFR <15ml/minute) are being managed without dialysis, either through their own preference or because dialysis is unlikely to benefit them. This growing group of patients has extensive health care needs. Their overall symptom burden is high, and symptom prevalence matches or exceeds that in other end of life populations, both with cancer and other non-cancer diagnoses. These symptoms may often go unrecognised and under-treated. Regular symptom assessment is necessary, together with pro-active management of identified symptoms. Pain can be managed using the principles of the World Health Organisation analgesic ladder. Not all opioid medications are recommended for these patients. Paracetamol, tramadol, and fentanyl are the most appropriate medications for steps 1, 2 and 3 respectively. There is limited evidence on the use of buprenorphine, oxycodone and hydromorphone. Methadone is safe but should only be prescribed by a clinician experienced in its use. Morphine and diamorphine are not recommended because of metabolite accumulation. Pruritus is also challenging to manage. The evidence for pharmacological interventions to alleviate pruritus is summarized, and a pragmatic approach to management suggested. Emollients, capsaisin cream, antihistamines, thalidomide and ondansetron may be helpful, according to the extent and pattern of pruritus. Symptoms may frequently be due to co-morbid conditions, not renal disease itself, and managing them is difficult because of the constraints on the use of medication which kidney failure imposes. Collaboration between renal and palliative specialists can help identify ways to achieve best care for these patients.

Exploring the clinical utility of blood ketone levels in the emergency department assessment of paediatric patients.

BACKGROUND: Ketonuria (on standard urine testing) is a frequent finding in children presenting to emergency departments. With the advent of hand-held ketone meters, blood ketone levels can now be rapidly quantified. HYPOTHESIS: Point of care testing (POCT) of blood ketone levels could provide clinically useful information on severity of illness in children and risk of hospital admission. METHODS: A prospective study using POCT of blood ketone levels in a convenience sample of children <13 years old, with a typical case mix of medical problems. FINDINGS: 186 children were studied. The range of ketone levels varied widely among this study population depending on the presenting complaint. Higher levels were noted in those presenting with anorexia or vomiting and fever. The median ketone level of the total study population was 0.2 (range 0-6.0, interquartile range 0.1-0.9) mmol/l. Ketone levels correlated poorly with discharge destination and duration of admission. However, receiver-operator characteristics for ketones as a predictor of admission were comparable to Pediatric Risk of Admission scores (area under the curve 0.64 and 0.72, respectively) and may represent an independent risk factor for admission. A ketone level >1.2 mmol/l has a positive predictive value of 66.7% for admission. Ketone levels correlated well with decreased oral intake (R2 = 0.25; p<0.001). CONCLUSIONS: A strong association was found between ketone levels, decreased oral intake and fever. Although ketone levels do not correlate well with more traditional markers of illness severity, they can help to predict the requirement for admission to hospital when interpreted in the context of the presenting illness. They may have applications in both the emergency department and primary care settings. Further prospective testing is required to validate these findings.

End-of-life care in end-stage renal disease: renal and palliative care.

The numbers of patients with end-stage renal disease are growing, with a disproportionate increase among those who are elderly, dependent and with multiple co-morbidities. More of these patients are choosing to be managed conservatively, without dialysis. Palliative provision for these patients within UK renal services is limited, but the recent National Service Framework for Renal Services (Department of Health, 2005) has promoted service development. However, few models of service provision have been described. This article describes a retrospective review of a new service for conservatively-managed patients with end-stage renal disease. The range and complexity of the health needs of this population is demonstrated, and an example of service development described. A model of the stages of the conservative pathway and appropriate interventions was developed. The absence of research evidence prevented development of formal audit standards, and highlighted the urgent need for evaluation of models of care.

Hypoxia-induced silencing of NMDA receptors in turtle neurons.

Hypoxia-induced suppression of NMDA receptors (NMDARs) in western painted turtle (Chrysemys picta) cortical neurons may be critical for surviving months of anoxic dormancy. We report that NMDARs are silenced by at least three different mechanisms operating at different times during anoxia. In pyramidal neurons from cerebrocortex, 1-8 min anoxia suppressed NMDAR activity (Ca(2+) influx and open probability) by 50-60%. This rapid decrease in receptor activity was controlled by activation of phosphatase 1 or 2A but was not associated with an increase in [Ca(2+)](i). However, during 2 hr of anoxia, [Ca(2+)](i) in cerebrocortical neurons increased by 35%, and suppression of NMDARs was predicted by the increase of [Ca(2+)](i) and controlled by calmodulin. An additional mechanism of NMDAR silencing, reversible removal of receptors from the cell membrane, was found in cerebrocortex of turtles remaining anoxic at 3 degrees C for 3-21 d. When suppression of NMDARs was prevented with phosphatase inhibitors, tolerance of anoxia was lost. Silencing of NMDARs is thus critical to the remarkable ability of C. picta to tolerate life without oxygen.

Serum mucin antigen (CASA) as a marker of amiodarone-induced pulmonary toxicity.

Amiodarone is used to treat life-threatening cardiac arrhythmias. Amiodarone-induced pulmonary toxicity (APT) can be difficult to diagnose. APT may result in increased mucus production and mucin expression. Thus, serum mucin-1 was evaluated as a marker for amiodarone-induced pulmonary toxicity. Concentrations of mucin-1 in peripheral blood were determined using cancer-associated serum antigen (CASA) assay in patients taking amiodarone. Eight of ten patients who developed major amiodarone toxicity had high serum CASA levels. Patients with toxicity had a significantly higher mean rank CASA concentration compared with those without major toxicity. CASA shows potential as a marker for amiodarone-induced toxicity, particularly pulmonary toxicity.

A cluster of melioidosis cases from an endemic region is clonal and is linked to the water supply using molecular typing of Burkholderia pseudomallei isolates.

Nine cases of melioidosis with four deaths occurred over a 28-month period in members of a small remote Aboriginal community in the top end of the Northern Territory of Australia. Typing by pulsed-field gel electrophoresis showed isolates of Burkholderia pseudomallei from six of the cases to be clonal and also identical to an isolate from the community water supply, but not to soil isolates. The clonality of the isolates found in this cluster contrasts with the marked genetic diversity of human and environmental isolates found in this region which is hyperendemic for B. pseudomallei. It is possible that the clonal bacteria persisted and were propagated in biofilm in the water supply system. While the exact mode of transmission to humans and the reasons for cessation of the outbreak remain uncertain, contamination of the unchlorinated community water supply is a likely explanation.

Neuroprotection and intracellular Ca2+ modulation with fructose-1,6-bisphosphate during in vitro hypoxia-ischemia involves phospholipase C-dependent signaling.

The neuroprotectant fructose-1,6-bisphosphate (FBP) preserves cellular [ATP] and prevents catastrophic increases in [Ca2+]i during hypoxia. Because FBP does not enter neurons or glia, the mechanism of protection is not clear. In this study, we show that FBP's capacity to protect neurons and stabilize [Ca2+]i during hypoxia derives from signaling by a phospholipase-C-intracellular Ca2+-protein kinases pathway, rather than Ca2+ chelation or glutamate receptor inhibition. FBP reduced [Ca2+]i changes in hypoxic hippocampal neurons, regardless of [Ca2+]e, and preserved cellular integrity as measured by trypan blue or propidium iodide exclusion and [ATP]. FBP also prevented hypoxia-induced increases in [Ca2+]i when glucose was absent and when [Ca2+]e was increased to negate Ca2+ chelation by FBP. These protective effects were observed equally in postnatal day 2 (P2) and P16 neurons. Inhibiting glycolysis with iodoacetate eliminated the protective effects of FBP in P16 neurons. FBP did not alter Ca2+ influx stimulated by brief applications of NMDA or glutamate during normoxia or hypoxia, but did reduce the increase in [Ca2+]i produced by 10 min of glutamate exposure during hypoxia. Because FBP increases basal [Ca2+]i and stimulates membrane lipid hydrolysis, we tested whether FBP's protective action was dependent on phospholipase C signaling. The phospholipase C inhibitor U73122 prevented FBP-induced increases in [Ca2+]i and eliminated FBP's ability to stabilize [Ca2+]i and increase survival during anoxia. Similarly, FBP's protection was eliminated in the presence of the mitogen/extracellular signal protein kinase (MEK) inhibitor U0126. We conclude that FBP may produce neuroprotection via activation of neuroprotective signaling pathways that modulate Ca2+ homeostasis.

Tribute to R. G. Boutilier: the role for skeletal muscle in the hypoxia-induced hypometabolic responses of submerged frogs.

Much of Bob Boutilier's research characterised the subcellular, organ-level and in vivo behavioural responses of frogs to environmental hypoxia. His entirely integrative approach helped to reveal the diversity of tissue-level responses to O(2) lack and to advance our understanding of the ecological relevance of hypoxia tolerance in frogs. Work from Bob's lab mainly focused on the role for skeletal muscle in the hypoxic energetics of overwintering frogs. Muscle energy demand affects whole-body metabolism, not only because of its capacity for rapid increases in ATP usage, but also because hypometabolism of the large skeletal muscle mass in inactive animals impacts so greatly on in vivo energetics. The oxyconformance and typical hypoxia-tolerance characteristics (e.g. suppressed heat flux and preserved membrane ion gradients during O(2) lack) of skeletal muscle in vitro suggest that muscle hypoperfusion in vivo is possibly a key mechanism for (i) downregulating muscle and whole-body metabolic rates and (ii) redistributing O(2) supply to hypoxia-sensitive tissues. The gradual onset of a low-level aerobic metabolic state in the muscle of hypoxic, cold-submerged frogs is indeed important for slowing depletion of on-board fuels and extending overwintering survival time. However, it has long been known that overwintering frogs cannot survive anoxia or even severe hypoxia. Recent work shows that they remain sensitive to ambient O(2) and that they emerge rapidly from quiescence in order to actively avoid environmental hypoxia. Hence, overwintering frogs experience periods of hypometabolic quiescence interspersed with episodes of costly hypoxia avoidance behaviour and exercise recovery. In keeping with this flexible physiology and behaviour, muscle mechanical properties in frogs do not deteriorate during periods of overwintering quiescence. On-going studies inspired by Bob Boutilier's integrative mindset continue to illuminate the cost-benefit(s) of intermittent locomotion in overwintering frogs, the constraints on muscle function during hypoxia, the mechanisms of tissue-level hypometabolism, and the details of possible muscle atrophy resistance in quiescent frogs.

The use of extracellular lactate as an oxidative substrate in the oxygen-limited frog.

The aim of this paper was to determine the contribution of anaerobic respiration to metabolism in hibernating frogs exposed to progressive hypoxia. Previous studies on acute exposure to hypoxia had shown that even at ambient PO2 levels of 60 mmHg, cold-submerged frogs were obliged to recruit anaerobic pathways to provide enough energy to maintain the ATP and phosphocreatine concentrations of tissues perfectly homeostatic. In the current experiments, we exposed frogs to hypoxic conditions gradually to reveal that 30 mmHg probably represents a 'threshold PO2' at which survival is still possible, at least for 1 week. However, by the time this threshold was reached, liver glycogen reserves were exhausted and the frog must rely thereafter on its quantitatively large store of skeletal muscle glycogen. The lactate produced as a by-product of glycolytic ATP production did not accumulate in the muscle but was preferentially exported to the plasma where it was held against a sizeable extracellular to intracellular gradient. The results suggest that the exported lactate was 'shuttled' between a poorly-perfused skeletal muscle and a more highly-perfused and oxygenated core of the animal where it could act as both a substrate for direct oxidation or for gluconeogenesis.

The protective effects of metabolic rate depression in hypoxic cold submerged frogs.

Aerobic metabolic rates (MO2) and respiratory quotients (RQ = MCO2/MO2) were measured in hypoxic frogs, hibernating underwater for up to 90 days at 3 degrees C. After 3 months of submergence at a PO2 of 50 mmHg, MO2 levels were 25% of those seen prior to hibernation. In progressive hypoxia, a gradual shift in RQ from 0.85 to 1.0 signaled an increasing reliance upon carbohydrate metabolism. Moreover, the glycogen concentrations of skeletal muscle, liver and heart of hypoxic frogs were more rapidly depleted than in their normoxic counterparts. A plasma lactacidosis revealed that the hypoxic animals recruited anaerobiosis to fuel a large 'Pasteur effect'. Throughout all stages of hypoxia, cellular ATP levels were maintained homeostatic. The ability to depress metabolic rate such that ATP demands can be met by oxidative phosphorylation in an oxygen limited environment is the key to the frogs' overwintering survival.

Factors affecting membrane permeability and ionic homeostasis in the cold-submerged frog.

Frogs (Rana temporaria) were submerged at 3 degrees C in either normoxic (P(O2)=155 mmHg, P(O2)=20 kPa) or hypoxic (P(O2)=60 mmHg; P(O2)=8 kPa) water for up to 16 weeks, and denied air access, to mimic the conditions of an ice-covered pond during the winter. The activity of the skeletal muscle Na(+)/K(+) pump over the first 2 months of hibernation, measured by ouabain-inhibitable (22)Na(+) efflux, was reduced by 30 % during normoxia and by up to 50 % during hypoxia. The reduction in Na(+)/K(+) pump activity was accompanied by reductions in passive (22)Na(+) influx and (86)Rb(+) efflux (effectively K(+) efflux) across the sarcolemma. This may be due to a decreased Na(+) permeability of the sarcolemma and a 75 % reduction in K(+) leak mediated by ATP-sensitive K(+) channels ('K(ATP)' channels). The lowered rates of (22)Na(+) and (86)Rb(+) flux are coincident with lowered transmembrane ion gradients for [Na(+)] and [K(+)], which may also lower Na(+)/K(+) pump activity. The dilution of extracellular [Na(+)] and intracellular [K(+)] may be partially explained by increased water retention by the whole animal, although measurements of skeletal muscle fluid compartments using (3)H-labelled inulin suggested that the reduced ion gradients represented a new steady state for skeletal muscle. Conversely, intracellular ion homeostasis within ventricular muscle was maintained at pre-submergence levels, despite a significant increase in tissue water content, with the exception of the hypoxic frogs following 4 months of submergence. Both ventricular muscles and skeletal muscles maintained resting membrane potential at pre-submergence levels throughout the entire period of hibernation. The ability of the skeletal muscle to maintain its resting membrane potential, coincident with decreased Na(+)/K(+) pump activity and lowered membrane permeability, provided evidence of functional channel arrest as an energy-sparing strategy during hibernation in the cold-submerged frog.

Respiratory, metabolic, and acid-base correlates of aerobic metabolic rate reduction in overwintering frogs.

Aerobic metabolic rates (MO2) and respiratory quotients (RQ = CO2 production/MO2) were measured contemporaneously in hibernating frogs Rana temporaria (L.), submerged for 90 days at 3 degrees C. After 3 mo of submergence in fully aerated water, MO2 levels were 61% of those seen at the same temperature before hibernation. Over the first 40 days of hibernation, RQ values (< or = 0.82) favored a lipid-based metabolism that progressively shifted to an exclusively carbohydrate metabolism (RQ = 1.01) by 90 days of hibernation. Liver glycogen concentrations fell by 68% during the first 8 wk of submergence, thereafter exhibiting a less rapid rate of utilization. Conversely, muscle glycogen concentrations remained stable over the first 2 mo of the experiment before falling by 33% over the course of the remaining 2 mo, indicating that the frog was recruiting muscle glycogen reserves to fuel metabolism. Submerged frogs exhibited an extracellular acidosis during the first week of submergence, but over the course of the next 15 wk "extracellular pH" values were not significantly different from the values obtained from the control air-breathing animals. The initial extracellular acidosis was not mirrored in the intracellular compartment, and the acid-base state was not significantly different from the control values for the first 8 wk. However, over the subsequent 8- to 16-wk period, the acid-base status shifted to a lower intracellular pH-HCO3 concentration set point, indicative of a metabolic acidosis. Even so, there was no indication that the acidosis could be attributed to anaerobic metabolism, as both plasma and muscle lactate levels remained low and stable. Muscle adenylate energy charge and lactate-to-pyruvate and creatine-to-phosphocreatine ratios also remained unchanged throughout hibernation. The capacity for profound metabolic rate suppression together with the ability to match substrate use to shifts in aerobic metabolic demands and the ability to fix new acid-base homeostatic set points are highly adaptive, both in terms of survival and reproductive success, to an animal that is often forced to overwinter under the cover of ice.