Whither lung EIT: where are we, where do we want to go and what do we need to get there?

Breathing moves volumes of electrically insulating air into and out of the lungs, producing conductivity changes which can be seen by electrical impedance tomography (EIT). It has thus been apparent, since the early days of EIT research, that imaging of ventilation could become a key clinical application of EIT. In this paper, we review the current state and future prospects for lung EIT, by a synthesis of the presentations of the authors at the 'special lung sessions' of the annual biomedical EIT conferences in 2009-2011. We argue that lung EIT research has arrived at an important transition. It is now clear that valid and reproducible physiological information is available from EIT lung images. We must now ask the question: How can these data be used to help improve patient outcomes? To answer this question, we develop a classification of possible clinical scenarios in which EIT could play an important role, and we identify clinical and experimental research programmes and engineering developments required to turn EIT into a clinically useful tool for lung monitoring.     

Application of a multi-route physiologically based pharmacokinetic model for manganese to evaluate dose-dependent neurological effects in monkeys

Manganese (Mn) is an essential element that is neurotoxic under certain exposure conditions. Monkeys and humans exposed to Mn develop similar neurological effects; thus, an improved understanding of the dose-response relationship seen in nonhuman primates could inform the human health risk assessment for this essential metal. A previous analysis of this dose-response relationship in experimental animals (Gwiazda, R., Lucchini, R., and Smith, D., 2007, Adequacy and consistency of animal studies to evaluate the neurotoxicity of chronic low-level manganese exposure in humans, J. Toxicol. Environ. Health Part A 70, 594-605.) relied on estimates of cumulative intake of Mn as the sole measure for comparison across studies with different doses, durations, and exposure routes. In this study, a physiologically based pharmacokinetic model that accurately accounts for the dose dependencies of Mn distribution was used to estimate increases in brain Mn concentrations in monkeys following Mn exposure. Experimental studies evaluated in the analysis included exposures by inhalation, oral, iv, ip, and sc dose routes, and spanned durations ranging from several weeks to over 2 years. This analysis confirms that the dose-response relationship for the neurotoxic effects of Mn in monkeys is independent of exposure route and supports the use of target tissue Mn concentration or cumulative target tissue Mn as the appropriate dose metric for these comparisons. These results also provide strong evidence of a dose-dependent transition in the mode of action for the neurological effects of Mn that needs to be considered in risk assessments for this essential metal.     

Biologics: the next generation of analgesic drugs?

For many decades, there have been few novel therapies for pain, and the number of promising targets that have been genuinely validated in the clinic is small. Discovery and development of biologic therapies for analgesia provides a better opportunity to test such targets, potentially providing new and effective therapies. Biologics have revolutionised the treatment of many diseases, with the greatest advances seen in oncology and inflammatory disorders. Across a broad spectrum of severe, chronic pain disorders - including inflammatory pain, neuropathic pain and cancer pain - biologics could offer patients safer and more-effective alternatives to currently available treatments. As such, progression of large-molecule therapies is becoming a strategic priority for companies as they look to advance their portfolios.     

Ca2+-Dependent Regulation of Ca2+ Currents in Rat Primary Afferent Neurons: Role of CaMKII and the Effect of Injury

Currents through voltage-gated Ca(2+) channels (I(Ca)) may be regulated by cytoplasmic Ca(2+) levels ([Ca(2+)](c)), producing Ca(2+)-dependent inactivation (CDI) or facilitation (CDF). Since I(Ca) regulates sensory neuron excitability, altered CDI or CDF could contribute to pain generation after peripheral nerve injury. We explored this by manipulating [Ca(2+)](c) while recording I(Ca) in rat sensory neurons. In uninjured neurons, elevating [Ca(2+)](c) with a conditioning prepulse (-15 mV, 2 s) inactivated I(Ca) measured during subsequent test pulses (-15 mV, 5 ms). This inactivation was Ca(2+)-dependent (CDI), since it was decreased with elimination of Ca(2+) influx by depolarization to above the I(Ca) reversal potential, with high intracellular Ca(2+) buffering (EGTA 10 mm or BAPTA 20 mm), and with substitution of Ba(2+) for extracellular Ca(2+), revealing a residual voltage-dependent inactivation. At longer latencies after conditioning (>6 s), I(Ca) recovered beyond baseline. This facilitation also proved to be Ca(2+)-dependent (CDF) using the protocols limiting cytoplasmic Ca(2+) elevation. Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) blockers applied by bath (KN-93, myristoyl-AIP) or expressed selectively in the sensory neurons (AIP) reduced CDF, unlike their inactive analogues. Protein kinase C inhibition (chelerythrine) had no effect. Selective blockade of N-type Ca(2+) channels eliminated CDF, whereas L-type channel blockade had no effect. Following nerve injury, CDI was unaffected, but CDF was eliminated in axotomized neurons. Excitability of sensory neurons in intact ganglia from control animals was diminished after a similar conditioning pulse, but this regulation was eliminated by injury. These findings indicate that I(Ca) in sensory neurons is subject to both CDI and CDF, and that hyperexcitability following injury-induced loss of CDF may result from diminished CaMKII activity.     

Emergency Neurological Life Support: Airway,Ventilation, and Sedation

Airway management is central to the resuscitation of the neurologically ill. These patients often have evolving processes that threaten the airway and adequate ventilation. Therefore, airway, ventilation, and sedation were chosen as an Emergency Neurological Life Support (ENLS) protocol. Reviewed topics include airway management; the decision to intubate; when and how to intubate with attention to cardiovascular status; mechanical ventilation settings; and the use of sedation, including how to select sedative agents based on the patient’s neurological status.     

Reducing the use of seclusion for mental disorder in a prison: implementing a high support unit in a prison using participant action research

Background

Vulnerable prisoners and mentally disordered offenders who present with risk of harm to self or others were accommodated in Special Observation Cells (SOCs) isolated from others for considerable periods of time. This practice has been criticised by the Council of Europe Committee for the Prevention of Torture. The objective of this initiative was to reduce the use of seclusion within the prison and to improve the care of vulnerable and mentally ill prisoners within the prison.

Results

The prison studied is a committal centre for sentenced prisoners with an official bed capacity of 630. The forensic mental health in-reach team, in co-operation with the prison health service followed the 'spiral' of planning, action and fact finding about the results of the action. In December 2010 a 10 bed High Support Unit (HSU) was established within the prison. During the first year, 96 prisoners were admitted. A third (35%) reported psychotic symptoms, 28% were referred due to the immediate risk of self-harm, 17% were accommodated for medical treatments and increased observation, 13% received specialised treatment by the Addiction Psychiatry team, 6% presented with emotional distress. One prisoner was accommodated on the HSU due to the acute risk he posed to others. A major mental illness was diagnosed in 29%, 20% required short-term increased support for crisis intervention and were found not to have a mental illness. A further 10% were deemed to be feigning symptoms of mental illness to seek refuge in the HSU. 7% had personality disorder as their primary diagnosis and 4% had a learning disability. Stratifying risk within the prison population through the provision of the HSU decreased the total episodes of seclusion in the prison by 59% (p < 0.001) in addition to providing a more effective psychiatric in-reach service to the prison. Pathways between the prison and the forensic psychiatric hospital saw no change in activity but improved continuity of care.

Conclusions

The next step is to further stratify risk by establishing a low support unit to serve as a step-down from the high support unit.

     

Cervical dystonia after ear surgery

BackgroundThe pathophysiology of primary focal dystonia remains insufficiently understood, but may be explained by a ‘double-lesion’ model, in which a particular trigger on top of an intrinsic susceptibility due to a certain genetic predisposition can induce dystonia.Case-reportHere, we describe a patient who developed cervical dystonia soon after ear surgery (revision stapedectomy), which had caused vestibular hypofunction.DiscussionWe also discuss other cases of dystonia associated with vestibular lesions and with other reported triggers, and put these into the context of the possible pathophysiology.     

A Content Analysis of Visual Cancer Information: Prevalence and Use of Photographs and Illustrations in Printed Health Materials

Researchers and practitioners have an increasing interest in visual components of health information and health communication messages. This study contributes to this evolving body of research by providing an account of the visual images and information featured in printed cancer communication materials. Using content analysis, 147 pamphlets and 858 images were examined to determine how frequently images are used in printed materials, what types of images are used, what information is conveyed visually, and whether or not current recommendations for the inclusion of visual content were being followed. Although visual messages were found to be common in printed health materials, existing recommendations about the inclusion of visual content were only partially followed. Results are discussed in terms of how relevant theoretical frameworks in the areas of behavior change and visual persuasion seem to be used in these materials, as well as how more theory-oriented research is necessary in visual messaging efforts.