Implications of nocebo in anaesthesia care.

Nocebo refers to non-pharmacological adverse effects of an intervention. Well-intended procedural warnings frequently function as a nocebo. Both nocebo and placebo are integral to the generation of 'real' treatment effects and their associated 'real' side-effects. They are induced or exacerbated by: context; negative expectancy; and negative conditioning surrounding treatment. Since the late 1990s, the neuroscience literature has repeatedly demonstrated that the nocebo effect is mediated by discrete neurobiological mechanisms and specific physiological modulations. Although no single biological mechanism has been found to explain the nocebo effect, nocebo hyperalgesia is thought to initiate from the dorsal lateral prefrontal cortex subsequently triggering the brain's descending pain modulatory system and other pain regulation pathways. Functional magnetic resonance imaging shows that expectation of increased pain is accompanied by increased neural activity in the hippocampus and midcingulate cortex which is not observed when analgesia is expected. Functional magnetic resonance imaging studies have shown that the anterior cingulate cortex is pivotal in the perception of affective pain evoked by nocebo words. Research has also explored neurotransmitters which mediate the nocebo effect. The neuropeptide cholecystokinin appears to play a key role in the modulation of pain by nocebo. Hyperalgesia generated by nocebo also increases the activity of the hypothalamic-pituitary-adrenal axis as indicated by increases in plasma cortisol. The avoidance or mitigation of nocebo needs to be recognised as a core clinical skill in optimising anaesthesia care. Embracing the evidence around nocebo will allow for phrases such as 'bee sting' and 'sharp scratch' to be thought of as clumsy verbal relics of the past. Anaesthesia as a profession has always prided itself on practicing evidence-based medicine, yet for decades anaesthetists and other healthcare staff have communicated in ways counter to the evidence. The premise of every interaction should be 'primum non nocere' (first, do no harm). Whether the context is research or clinical anaesthesia practice, the nocebo can be ignored no longer.

Anaesthesia-related haemodynamic complications in Williams syndrome patients: a review of one institution's experience.

Williams syndrome is a genetic disorder associated with cardiac pathology, including supravalvular aortic stenosis and coronary artery stenosis. Sudden cardiac death has been reported in the perioperative period and attributed to cardiovascular pathology. In this retrospective audit, case note and anaesthetic records were reviewed for all confirmed Williams syndrome patients who had received an anaesthetic in our institution between July 1974 and November 2009. There were a total of 108 anaesthetics administered in 29 patients. Twelve of the anaesthetics (11.1%) were associated with cardiac complications including cardiac arrest in two cases (1.85%). Of the two cardiac arrests, one patient died within the first 24 hours postanaesthetic and the other patient survived, giving an overall mortality of 0.9% (3.4%). We conclude that Williams syndrome confers a significant anaesthetic risk, which should be recognised and considered by clinicians planning procedures requiring general anaesthesia.

Nerve sheath catheter analgesia for forequarter amputation in paediatric oncology patients.

In a single centre over two years, four children (7 to 10 years old) with upper limb osteosarcoma underwent chemotherapy followed by forequarter amputation. All patients had preoperative pain and were treated with gabapentin. Nerve sheath catheters were placed in the brachial plexus intraoperatively and left in situ for five to 14 days. After surgery, all patients received local anaesthetic infused via nerve sheath catheters as part of a multimodal analgesia technique. Three of the four patients were successfully treated as outpatients with the nerve sheath catheters in situ. All four children experienced phantom limb pain; however, it did not persist beyond four weeks in any patient.

Long-term use of nerve block catheters in paediatric patients with cancer related pathologic fractures.

We report three cases of children with osteosarcoma and pathologic fractures treated with long-term continuous nerve blocks for preoperative pain control. One patient with a left distal femoral diaphysis fracture had a femoral continuous nerve block catheter for 41 days without complications. Another with a fractured left proximal femoral shaft had three femoral continuous nerve block catheters for 33, 26 and 22 days respectively. The third patient, whose right proximal humerus was fractured, had a brachial plexus continuous nerve block catheter for 36 days without complication. In our experience, prolonged use of continuous nerve block is safe and effective in children with pathologic fractures for preoperative pain control.

Antenatal management of the expectant mother and extreme preterm infant at the limits of viability.

We explored the opinions of healthcare providers on the antenatal management and outcome of preterm delivery at less than 28 weeks gestation. An anonymous postal questionnaire was sent to health care providers. The response rate was 55% (74% Obstetrician, 70% neonatologist). Twenty four weeks is the limit at which most would advocate intervention. At 23 weeks 67% of neonatologists advocate antenatal steroids. 50% of all health care providers advocate cardiotocographic monitoring at 24 weeks gestation. Written information on survival and long-term outcome is provided by 8% of the respondents. Neonatologists (50%) were more likely than obstetrician (40%) to advocate caesarean section at 25 weeks. We conclude that 24 weeks is the limit at which most would advocate intervention. Significant variation exists both between and within each health care group at less than 25 weeks. Establishment and provision of national outcome data may aid decision making at the limits of viability.

Continuous tunnelled femoral nerve block for palliative care of a patient with metastatic osteosarcoma.

An 18-year-old man with metastatic femoral osteosarcoma had inadequate pain control with gabapentin, naproxen and intravenous fentanyl. A tunnelled femoral nerve catheter was used to administer a continuous infusion of 0.2% ropivacaine and 4 microg/ml clonidine (10 ml/hour) until his death 88 days later During discharge from hospital, catheter disconnection resulted in severe pain and readmission. Tunnelling, aseptic insertion technique, antibiotics and sterile infusate prepared by the pharmacy may have reduced the chance of infection. We propose that this is a suitable and effective technique in the long-term management of patients with terminal cancer and should be considered on a case-by-case basis.

An international survey of EEG use in the neonatal intensive care unit.

OBJECTIVE: To examine the extent of EEG monitoring in neonatal intensive care units (NICUs), and to survey the level of experience and training of those using it. STUDY DESIGN: A web-based survey, the link to which was circulated via e-mail, personal contact, specialist societies and professional groups. Survey data were exported to SPSS for analysis. RESULTS: In total 210 surveys were analysed; 124 from Europe, 54 from the US. Ninety percent of respondents had access to either EEG or aEEG monitoring; 51% had both. EEG was mainly interpreted by neurophysiologists (72%) whereas aEEG was usually interpreted by neonatologists (80%). Only 9% of respondents reported that they felt 'very confident' in their ability to interpret aEEG/EEG with 31% reporting that they were 'not confident'. Half had received no formal training in EEG. CONCLUSION: Both aEEG and conventional EEG were used extensively in the NICUs surveyed for this study. Most of the survey respondents were not confident in their ability to interpret EEGs despite the fact that they used monitoring routinely. There is an urgent need for a structured and appropriately targeted training programme in EEG methodologies and EEG interpretation for neonatal intensive care unit staff.

Resuscitation at the limits of viability--an Irish perspective.

BACKGROUND: Advances in neonatal care continue to lower the limit of viability. Decision making in this grey zone remains a challenging process. OBJECTIVE: To explore the opinions of healthcare providers on resuscitation and outcome in the less than 28-week preterm newborn. DESIGN/METHODS: An anonymous postal questionnaire was sent to health care providers working in maternity units in the Republic of Ireland. Questions related to neonatal management of the extreme preterm infant, and estimated survival and long-term outcome. RESULTS: The response rate was 55% (74% obstetricians and 70% neonatologists). Less than 1% would advocate resuscitation at 22 weeks, 10% of health care providers advocate resuscitation at 23 weeks gestation, 80% of all health care providers would resuscitate at 24 weeks gestation. 20% of all health care providers would advocate cessation of resuscitation efforts on 22-25 weeks gestation at 5 min of age. 65% of Neonatologists and 54% trainees in Paediatrics would cease resuscitation at 10 min of age. Obstetricians were more pessimistic about survival and long term outcome in newborns delivered between 23 and 27 weeks when compared with neonatologists. This difference was also observed in trainees in paediatrics and obstetrics. CONCLUSION: Neonatologists, trainees in paediatrics and neonatal nurses are generally more optimistic about outcome than their counterparts in obstetrical care and this is reflected in a greater willingness to provide resuscitation efforts at the limits of viability.

Rapid preparation of cyanobacterial DNA for real-time PCR analysis.

AIMS: To develop a rapid preparation method for real-time PCR analysis of cyanobacteria from cultures or field samples. METHODS AND RESULTS: Field samples and cultures containing Anabaena circinalis, Cylindrospermopsis raciborskii or Microcystis aeruginosa were subjected to three cell disruption treatments: (i) heating during thermocycling, (ii) microwave irradiation in the presence of detergent and (iii) probe sonication. Treated samples were directly added to the PCR reaction and analysed on two different real-time devices. A statistically significant difference was evident in the cycle thresholds for each of the treatments in all but one culture and one environmental sample, sonication and microwave treatments performing better than direct addition. The microwave treatment was also compared to the Qiagen DNA Mini kit and performance was equivalent when treated samples were analysed as above. CONCLUSIONS: Whilst microwave treatment was slightly less effective than probe sonication across all samples, it was more amenable to processing multiple samples and significantly better than heat treating the sample during thermocycling. SIGNIFICANCE AND IMPACT OF THE STUDY: The microwave method described here is a simple, rapid and effective preparation method for cyanobacterial DNA that can be easily deployed in the field, making the most of the speed and flexibility offered by fixed and portable real-time PCR devices.

Unsuccessful lumbar puncture in a paediatric patient with achondroplasia.

We present a case of an unsuccessful lumbar puncture performed on an anaesthetised 17-year-old girl with achondroplasia who was diagnosed with and being treated for acute lymphoblastic leukaemia. Magnetic resonance imaging (MRI) subsequently showed spinal stenosis and no observable cerebrospinal fluid around the nerve roots at the levels of the lumbar pedicles and discs. A recommendation is made to obtain MRI scans before proceeding with lumbar puncture and/or spinal anaesthesia in this patient group to ensure that the anatomical features of the insertion site are favourable to a successful outcome.

Walking in a city neighbourhood, paving the way.

BACKGROUND: There is an increasing interest in the use of walking routes to promote physical activity. We explored the stated attitudes of selected residents from two adjacent low-income city neighbourhoods towards walking. This was in response to negative results obtained in a quantitative study assessing the impact of the Slí-na-Sláinte (path to health), a signed heart health walking route. METHOD: This was a qualitative focus group study. RESULTS: The impact of the walking route was marginal. Four major themes influencing local walking emerged, centring on the social and physical environment. CONCLUSION: Findings suggest that the neighbourhoods are unreceptive to health promotion initiatives such as the Slí-na-Sláinte since residents are dealing with fundamental social and physical environmental issues. Initiatives such as the Slí-na-Sláinte need to be embedded in a supportive and facilitative environment if they are to achieve substantial impact.

Collecting, archiving and processing DNA from wildlife samples using FTA databasing paper.

BACKGROUND: Methods involving the analysis of nucleic acids have become widespread in the fields of traditional biology and ecology, however the storage and transport of samples collected in the field to the laboratory in such a manner to allow purification of intact nucleic acids can prove problematical. RESULTS: FTA databasing paper is widely used in human forensic analysis for the storage of biological samples and for purification of nucleic acids. The possible uses of FTA databasing paper in the purification of DNA from samples of wildlife origin were examined, with particular reference to problems expected due to the nature of samples of wildlife origin. The processing of blood and tissue samples, the possibility of excess DNA in blood samples due to nucleated erythrocytes, and the analysis of degraded samples were all examined, as was the question of long term storage of blood samples on FTA paper. Examples of the end use of the purified DNA are given for all protocols and the rationale behind the processing procedures is also explained to allow the end user to adjust the protocols as required. CONCLUSIONS: FTA paper is eminently suitable for collection of, and purification of nucleic acids from, biological samples from a wide range of wildlife species. This technology makes the collection and storage of such samples much simpler.

Photosensitizer initiated attacks on DNA under dry conditions and their inhibition: a DNA archiving issue.

Long-term aging of dry DNA is thought to be due to the attack of diverse cascades of reactive species with probably, no one single initiator of the cascades explaining all circumstances. Photosensitizer-initiated reactions from methylene blue and riboflavin were used to generate two model systems of reactive species around dry DNA in order to understand such systems and how to block them. Damage was assessed using plasmid DNA as a substrate with an in-situ microgel electrophoretic technique. Photodynamic methylene blue damage to DNA was very oxygen dependent but not that of riboflavin. This indicates that indirect type II pathways, probably via singlet oxygen were important for methylene blue but not for riboflavin. In both the absence and presence of oxygen, the DNA protection offered by dry caffeine and urate to both photodynamic agents indicated that most DNA attack was via electrophilic species. Overall, protection of dry archived DNA from spontaneously reactive species such as free radicals appears to be a real issue and, as expected, the predominant species in air appear to involve oxygen but not exclusively or necessarily so.

Species identity: conserved inverted LINE repeat clusters (ILRC) in the vertebrate genome as indicators of population boundaries.

The avian LINE CR1 generates multiply-superimposed insertions, resulting in apparently fortuitous inverted LINE repeat clusters (ILRCs). These loci display size micro-heterogeneity within populations, with few or no presence/absence polymorphisms, and yet only very closely related species share loci. Whilst the CR1 sequences that the ILRC loci are derived from are not species-specific, the loci themselves appear to be species-characteristic if not totally species specific. The mammalian LINE L1 is shown to act similarly to CR1 and also forms ILRCs. It is proposed that whilst the formation of these loci may be from a near-random process of super-insertion certain of them are in some way functional, explaining their conservation and rapid spread to population boundaries, whilst non-functional or inactive loci are quickly lost. ILRCs appear to decay from the element as formed by the accumulation of point mutations. ILRCs appear to an unusual example of non-polymorphic sequences being younger than polymorphic sequences with no obvious selective reason.

Laryngeal mask vs intubating laryngeal mask: insertion and ventilation by inexperienced resuscitators.

The laryngeal mask airway (LMA) has been shown to be useful in airway maintenance during resuscitation. The intubating laryngeal mask (ILM) is a modified LMA permitting both ventilation and rapid endotracheal intubation. We aimed to compare the LMA and the ILM with regard to ease of insertion and successful ventilation by inexperienced personnel. We have used anaesthetized, apnoeic, non-paralysed patients as a model to simulate resuscitation. Following standardized training, non-anaesthetic medical staff with no previous experience in laryngeal mask airway insertion (novices) inserted either the LMA or ILM in 55 patients following induction of anaesthesia. There were no differences between the two patient groups included in our study with regard to mean age and body mass index (BMI). The success rate for inserting the airway device and achieving a significant end-tidal CO2 recording within two minutes was 23/28 for the LMA (82.1%) and 22/27 for the ILM (81.5%). Reasons for failure included inability to insert the ILM past the teeth and insertion of the LMA upside down. There were no clinically relevant differences in the mean time to airway insertion and successful ventilation (62.6 vs 62 seconds) or expired tidal volume (781 vs 767 ml) for the LMA and ILM respectively. We conclude that the ILM is as easily inserted and effectively used as an LMA by novices and, because it allows the option offacilitating endotracheal intubation, may be the preferred device for maintaining an airway during resuscitation.

Reverse transcription of an RNA genome from databasing paper (FTA(R)).

The instability of RNA in solutions during storage and travel is an impediment to its utilization in routine diagnostics. A robust and simple approach to the problem of RNA protection and processing is offered by storage of RNA desiccated with processing procedures that do not solublize the RNA until the beginning of reverse transcription. The feasibility of this general approach was tested with coxsackievirus B4 (CVB-4) from blood or culture fluid held on a storage and transport medium (FTA(R)) and analysed by reverse transcriptase PCR (RT-PCR) without removing the RNA from the FTA(R) until reverse transcription. Phase-trapping techniques based on water-miscible solvents such as ethanol or phenol were compared with simple buffers and concentrated lithium chloride solutions. RT-PCR detection of viral RNA reached a sensitivity of approximately 0.1 fg, which is comparable with other non-nested PCR techniques. Whole blood as a virus vehicle significantly interfered with CVB-4 detection, but to an acceptable degree. Desiccation-storage of the RNA of CVB-4 appears to be unaffected by weeks on the storage medium under ambient conditions. These characteristics indicate that this approach forms a credible developmental base for RNA-based pathogen diagnostics with particular application to the problem of transporting potentially infectious body fluids to a centralized laboratory for analysis.

The mechanisms of pyknosis: hypercondensation and death.

Intense nuclear condensation with intense refractivity (pyknosis) is the ubiquitous terminus of all apoptosis and some necrosis of vertebrate cells, but its structural basis is unknown. Intense condensations were induced in a model system, the avian erythrocyte, and three different molecular processes distinguished from each other. Two of the hypercondensations, nucleolytic pyknosis, as in mammalian apoptosis, and anucleolytic pyknosis, as in necrosis, appear to be energetically spontaneous and appear to have a conformational basis with the third hypercondensation being a trans-nuclear membrane osmotic pressure compression effect. Nucleolytic pyknosis as per apoptosis was not intrinsic in this system and required exogenous nuclease. The pure anucleolytic pyknosis supported by this system was not induced by the apoptopic induction agents, staurosporine or antitopoisomerases (I and II), indicating a simple but unusual signaling pathway for anucleolytic pyknosis. Molecular weight determinations of the H5, H3, H4, H2a, and H2b, with final errors of +/-1 Da or less, seem to eliminate histone modifications as the basis of anucleolytic pyknosis. The molecular basis of pyknosis is proposed to be from internucleosomal rotational angle freedom that permits internucleosomal sharing of basic histone tails of adjacent nucleosomes and nucleofilaments. Much of the favorable conformational energy of pyknosis may be from the entropy increase of tail delocalization.