Alpha2 Antagonist Vatinoxan Does Not Abolish the Preconditioning Effect of Dexmedetomidine on Experimental Ischaemia-Reperfusion Injury in the Equine Small Intestine.

Pharmacological preconditioning with dexmedetomidine has been shown to ameliorate intestinal ischaemia reperfusion injury in different species, including horses. However, it remains unknown if this effect is related to alpha2 adrenoreceptor activity. Therefore, the aim of this study was to determine the effect of dexmedetomidine preconditioning with and without the administration of the peripheral alpha2 antagonist vatinoxan. This prospective randomized experimental trial included 12 horses equally divided between two treatment groups. Horses in group Dex received a bolus of dexmedetomidine followed by a continuous rate infusion (CRI), while group DexV additionally received vatinoxan as bolus and CRI. A median laparotomy was performed under general anaesthesia, and jejunal ischaemia was applied for 90 min, followed by 30 min of reperfusion. Mucosal damage was evaluated in full thickness biopsies by use of a semiquantitative mucosal injury score and by determining the apoptotic cell counts with immunohistochemical staining for cleaved caspase-3 and TUNEL. Comparisons between the groups and time points were performed using non-parametric tests (p < 0.05). During pre-ischaemia and ischaemia, no differences could be found in mucosal injury between the groups. After reperfusion, group DexV showed lower mucosal injury scores compared to group Dex. The apoptotic cell counts did not differ between the groups. In conclusion, antagonizing the peripheral alpha2 adrenoreceptors did not negatively affect dexmedetomidine preconditioning.

Development of a patient journey map for people living with cervical dystonia.

BACKGROUND: Patient journey maps are increasingly used as a tool that enables healthcare providers to refine their service provision to best meet patient needs. We developed a cervical dystonia patient journey map (CDPJM) that describes the holistic patient experience from pre-diagnosis through to long-term treatment. METHODS: The CDPJM was developed in 2 stages; a patient survey (open questions and multichoice) of 15 patients with CD was conducted to inform the design of the CDPJM, which was then refined and validated by an expert-patient focus group. RESULTS: Qualitative analysis of the patient survey supported five key stages of the patient journey: symptom onset, diagnosis and therapeutic relationship with healthcare professionals, initiation of care for CD, start of CD treatment, and living with treated CD. Following symptom onset, survey respondents described having multiple visits to their family doctor who prescribed strong pain killers and muscle relaxants and referred their patient to up to 10 different specialists for diagnosis. Over half (53.3%) of respondents had received ≥ 1 misdiagnosis. Respondents reported relief at having a diagnosis but a lack of understanding of the prognosis and treatment options; 46.7% said their neurologist did not spend enough time addressing their concerns. Survey respondents reported using a variety of alternative sources of information, including the internet (86.7%), self-help groups (66.7%) and information leaflets provided by health care professionals (60.0%). While botulinum toxin (BoNT) was consistently discussed as the main treatment option, some neurologists also mentioned physiotherapy, counselling, and other complementary approaches. However, patients were often left to seek complementary services themselves. Patients reported a 'rollercoaster' of relief with BoNT treatment with symptoms (and subsequent impact on daily life) returning towards the end of an injection cycle. "When BoNT works well I can return to an almost normal life … when the injections stop working so well, I have to rest more and avoid going to work and experience life restrictions." CONCLUSIONS: We present the first patient journey map for CD that can be used to guide local service mapping and to compare current provision with what patients say they want and need.

Preconditioning with lidocaine and xylazine in experimental equine jejunal ischaemia.

BACKGROUND: Pharmacological preconditioning of dexmedetomidine on small intestinal ischaemia/reperfusion injury has been reported in different animal models including horses. OBJECTIVES: The objective was to assess if xylazine and lidocaine have a preconditioning effect in an experimental model of equine jejunal ischaemia. STUDY DESIGN: Terminal in vivo experiment. METHODS: Ten horses under general anaesthesia were either preconditioned with xylazine (group X; n = 5) or lidocaine (group L; n = 5). A historical untreated control group (group C; n = 5) was used for comparison. An established experimental model of equine jejunal ischaemia was applied, and intestinal samples were taken pre-ischaemia, after ischaemia and following reperfusion. Histomorphological examination was performed based on a modified Chiu score. Immunohistochemical staining for cleaved caspase-3, TUNEL and calprotectin was performed, and positive cell counts were expressed in cells/mm2 . RESULTS: There was no progression of histomorphological mucosal injury from ischaemia to reperfusion, and there were no differences in histomorphology between the groups. After ischaemia, group X had significantly less caspase-positive cells compared to the control group with a median difference of 227% (P = .01). After reperfusion, group X exhibited significantly lower calprotectin-positive cell counts compared to the control group, with a median difference of 6.8 cells/mm2 in the mucosa and 44 cells in the serosa (P = .02 and .05 respectively). All groups showed an increase in caspase- and calprotectin-positive cells during reperfusion (P < .05). TUNEL-positive cells increased during ischaemia, followed by a decrease after reperfusion (P < .05). MAIN LIMITATIONS: The small sample size and the use of a historical control group. Preconditioning effects of the tested drugs may be masked by the protective effects of isoflurane in the anaesthetic protocol. CONCLUSIONS: Preconditioning with lidocaine did not have any effect on the tested variables. The lower cell counts of caspase- and calprotectin-positive cells in group X may indicate a beneficial effect of xylazine on ischaemia/reperfusion injury. Due to the absence of a concurrent reduction of histomorphological injury, the clinical significance remains uncertain.

Ischaemic preconditioning and pharmacological preconditioning with dexmedetomidine in an equine model of small intestinal ischaemia-reperfusion.

Small intestinal strangulation associated with ischaemia-reperfusion injury (IRI) is common in horses. In laboratory animals IRI can be ameliorated by ischaemic preconditioning (IPC) and pharmacological preconditioning (PPC) with dexmedetomidine. The aim of this study was to determine the effect of PPC with dexmedetomidine or IPC in an equine model of small intestinal ischaemia-reperfusion (IR). In a randomized controlled experimental trial, 15 horses were assigned to three groups: control (C), IPC, and PPC with dexmedetomidine (DEX). All horses were placed under general anaesthesia and 90% jejunal ischaemia was induced for 90 minutes, followed 30 minutes of reperfusion. In group IPC, three short bouts of ischaemia and reperfusion were implemented, and group DEX received a continuous rate infusion of dexmedetomidine prior to the main ischaemia. Jejunal biopsies were collected before ischaemia (P), and at the end of ischaemia (I) and reperfusion (R). Mucosal injury was assessed by the Chiu-Score, inflammatory cells were stained by cytosolic calprotectin. The degree of apoptosis and cell necrosis was assessed by cleaved-caspase-3 and TUNEL. Parametric data were analyzed by two-way ANOVA for repeated measurements followed by Dunnetts t-test. Non parametric data were compared between groups at the different time points by a Kruskal-Wallis-Test and a Wilcoxon-2-Sample-test. The mucosal injury score increased during I in all groups. After reperfusion, IRI further progressed in group C, but not in IPC and DEX. In all groups the number of cleaved caspase-3 and TUNEL positive cells increased from P to I. The number of TUNEL positive cells were lower in group DEX compared to group C after I and R. Infiltration with calprotectin positive cells was less pronounced in group DEX compared to group C, whereas in group IPC more calprotectin positive cells were seen. In conclusion, IPC and DEX exert protective effects in experimental small intestinal ischaemia in horses.

New life for old wires: electrochemical sensor method for neural implants.

OBJECTIVE: Electrochemical microsensors based on noble metals can give essential information on their microenvironment with high spatio-temporal resolution. However, most advanced chemo- and biosensors lack the long-term stability for physiological monitoring of brain tissue beyond an acute application. Noble metal electrodes are widely used as neural interfaces, particularly for stimulating in the central nervous system. Our goal was to recruit already deployed, unmodified noble metal electrodes (Pt, Pt/Ir) as in situ chemical sensors. APPROACH: With advanced electrochemical sensor methods, we investigated electrode surface processes, oxidizable species and oxygen as an indicator for tissue mass transport. We developed a unique, multi-step, amperometric/potentiometric sensing procedure derived from the investigation of Pt surface processes by chronocoulometry providing fundamental characterization of the electrode itself. MAIN RESULTS: The resulting electrochemical protocol preconditions the electrode, measures oxidizable and reducible species, and the open circuit potential (OCP). A linear, stable sensor performance was demonstrated, also in the presence of proteins, validating signal stability of our cyclic protocol in complex environments. We investigated our sensor protocol with microelectrodes on custom Pt/Ir-wire tetrodes by in vivo measurements in the rat brain for up to four weeks. Results showed that catalytic activity of the electrode is lost over time, but our protocol is repeatedly able to both quantify and restore electrode sensitivity in vivo. SIGNIFICANCE: Our approach is highly relevant because it can be applied to any existing Pt electrode. Current methods to assess the brain/electrode microenvironment mainly rely on imaging techniques, histology and analysis of explanted devices, which are often end-point methods. Our procedure delivers online and time-transient information on the chemical microenvironment directly at the electrode/tissue interface of neural implants, gives new insight into the charge transfer processes, and delivers information on the state of the electrode itself addressing long-term electrode degradation.

Characteristics, changes and influence of body composition during a 4486 km transcontinental ultramarathon: results from the TransEurope FootRace mobile whole body MRI-project.

BACKGROUND: Almost nothing is known about the medical aspects of runners doing a transcontinental ultramarathon over several weeks. The results of differentiated measurements of changes in body composition during the Transeurope Footrace 2009 using a mobile whole body magnetic resonance (MR) imager are presented and the proposed influence of visceral and somatic adipose and lean tissue distribution on performance tested. METHODS: 22 participants were randomly selected for the repeated MR measurements (intervals: 800 km) with a 1.5 Tesla MR scanner mounted on a mobile unit during the 64-stage 4,486 km ultramarathon. A standardized and validated MRI protocol was used: T1 weighted turbo spin echo sequence, echo time 12 ms, repetition time 490 ms, slice thickness 10 mm, slice distance 10 mm (breath holding examinations). For topographic tissue segmentation and mapping a modified fuzzy c-means algorithm was used. A semi-automatic post-processing of whole body MRI data sets allows reliable analysis of the following body tissue compartments: Total body volume (TV), total somatic (TSV) and total visceral volume (TVV), total adipose (TAT) and total lean tissue (TLT), somatic (SLT) and visceral lean tissue (VLT), somatic (SAT) and visceral adipose tissue (VAT) and somatic adipose soft tissue (SAST). Specific volume changes were tested on significance. Tests on difference and relationship regarding prerace and race performance and non-finishing were done using statistical software SPSS. RESULTS: Total, somatic and visceral volumes showed a significant decrease throughout the race. Adipose tissue showed a significant decrease compared to the start at all measurement times for TAT, SAST and VAT. Lean adipose tissues decreased until the end of the race, but not significantly. The mean relative volume changes of the different tissue compartments at the last measurement compared to the start were: TV -9.5% (SE 1.5%), TSV -9.4% (SE 1.5%), TVV -10.0% (SE 1.4%), TAT -41.3% (SE 2.3%), SAST -48.7% (SE 2.8%), VAT -64.5% (SE 4.6%), intraabdominal adipose tissue (IAAT) -67.3% (SE 4.3%), mediastinal adopose tissue (MAT) -41.5% (SE 7.1%), TLT -1.2% (SE 1.0%), SLT -1.4% (SE 1.1%). Before the start and during the early phase of the Transeurope Footrace 2009, the non-finisher group had a significantly higher percentage volume of TVV, TAT, SAST and VAT compared to the finisher group. VAT correlates significantly with prerace training volume and intensity one year before the race and with 50 km- and 24 hour-race records. Neither prerace body composition nor specific tissue compartment volume changes showed a significant relationship to performance in the last two thirds of the Transeurope Footrace 2009. CONCLUSIONS: With this mobile MRI field study the complex changes in body composition during a multistage ultramarathon could be demonstrated in detail in a new and differentiated way. Participants lost more than half of their adipose tissue. Even lean tissue volume (mainly skeletal muscle tissue) decreased due to the unpreventable chronic negative energy balance during the race. VAT has the fastest and highest decrease compared to SAST and lean tissue compartments during the race. It seems to be the most sensitive morphometric parameter regarding the risk of non-finishing a transcontinental footrace and shows a direct relationship to prerace-performance. However, body volume or body mass and, therefore, fat volume has no correlation with total race performances of ultra-athletes finishing a 4,500 km multistage race.

Analysis of intracranial pressure time series using wavelets (Haar basis functions).

PURPOSE: Transforming intracranial pressure (ICP) into frequency domain commenced in the early 1980s, arriving at the conclusion that cerebrospinal dynamics were mapped by ICP spectral composition. Classical analysis tools were not suitable for handling intrinsic signal non-stationarity. To overcome inherent obstacles we introduce a novel approach based upon wavelets. METHODS: During routine diagnostic volume pressure testing epidural ICP was acquired in 118 patients with suspected cerebrospinal fluid circulatory disorders. Pressure was digitised and conditioned to separate low frequent signal components (

Stationarity in neuromonitoring data.

PURPOSE: Signals reflecting the metabolic and circulatory status of an injured central nervous system are normally corrupted systematically. The patient is part of a therapeutic control-loop and the signals acquired are rather determined by the quality of control (stationarity of signals) than by the underlying pathological process. METHODS: To verify the control-loop hypothesis, neuromonitoring data from 12 randomly selected severely head injured patients (initial GCS ≤ 8, 7 men, 5 women) were analysed for circulatory (blood pressure, intracranial pressure [ICP], cerebral perfusion pressure [CPP]) and metabolic (arterial blood gases, jugular bulb oxygenation [SjvO(2)], brain tissue oxygen partial pressure [ptiO(2)]) variables (n = 10). A total of 120 time series of generally not equidistant sample intervals were assessed for stationarity by Wallis & Moore's runs test. RESULTS: Non-stationarity could only be proven in 23 time series, i.e. the control-loop hypothesis was violated. Trends were mainly found in CPP (n = 5) and ICP (n = 4). The remaining cases spread out on all but one (temperature) signal. Nine patients showed at least one time series with a trend. One patient had clear trends in five out of ten variables that focused on SjvO(2), ptiO(2), ICP and CPP. CONCLUSIONS: Absence of stationarity in about 20% of time series is credited to an effective therapeutic control-loop. For analytical purposes, however, the benefit seems to be overestimated. Consequently, neuromonitoring should be considered the analysis of short-term disturbances that are intentionally compensated for by a short response time. Information content is thus reduced even if the number of sensor devices increases.

Head trauma in children, part 3: clinical and psychosocial outcome after head trauma in children.

With the aim of determining long-term outcome, the authors approached 38 families (average 2.1 years after trauma) with a questionnaire, following the acute-clinical treatment of head trauma of their children. Long-term damage was restricted almost exclusively to patients presenting with a Glasgow Coma Score < or =8. Paresis (16%), cranial nerve damage (13%), incontinence (5%), or coordinative disturbances (18%) continued. The older children stated that they influenced their life to a great extent (11%). Furthermore, many had mental and cognitive problems that occur quite frequently even in children with light head trauma and often only manifest after release from hospital. This causes problems and results in inferior performance (26%), especially at school, which is further complicated through lengthy periods of absence. The parents, especially, mentioned behavioral problems such as social withdrawal or aggressive demeanor, which led to tension also inside the family. A persistent vegetative state is rare after head trauma in children.

Head trauma in children, part 1: admission, diagnostics, and findings.

The objective of this study is to describe and to determine the preclinical situation and early in-clinical situation, diagnostic findings, and factors influencing the outcome of severe head trauma in children. Records of 48 children (0-16 years) were analyzed during a 3-year interval. Correlations with the outcome (Glasgow Outcome Scale) were determined by focusing on different scales, clinical findings, biochemistry, and clinical course features. The initial shock index had a major relevance (P = .0089). Systolic blood pressure (P = .0002) and bradycardia (P = .035) were important factors. Assessing the severity of trauma according to the Glasgow Coma Score, the most accurate parameter for outcome is based on the detailed quality of ''eye opening'' (P = .0155). Pupillary motoricity at the accident site (P = .002) and emergency room (P = .0004) are strong predictors. Preclinical measurements of stabilization and oxygenation have the same impact as the in-clinical management.

Head trauma in children, part 2: course and discharge with outcome.

To minimize the secondary brain damage, we analyzed the effect of cerebral perfusion pressure-orientated management and tried to find factors of clinical management and biochemical findings that influence clinical, cognitive, and psychosocial outcome. Management at intensive care unit was standardized. A standardized (short form 36 health survey) and nonstandardized split questionnaire explored long-term outcome. Glutamic-oxaloacetic-transaminase, creatine kinase MB or glucose are markers for bad outcome (P < .05). Patients with cerebral perfusion pressure values below the recommended standard for just a single occurrence had significantly worse outcome (P = .0132). Mean arterial pressure, central venous pressure, and heart rate alone do not correlate with outcome. At least 1 occurrence of mean arterial pressure and central venous pressure below the lower limits resulted in a poor outcome (P = .035). Cerebral perfusion pressure-guided therapy seems to prevent further brain damage and results in outcome scores that are comparable to those children with head trauma exhibiting symptoms of mild brain edema.

The use of recombinant activated factor VII in neurosurgery.

BACKGROUND: Bleeding complications in neurosurgery often take alarming proportions without major hemodynamic effect or impairment of coagulation physiology because severe neurologic deficits are to be expected. Any measures used to stabilize or normalize coagulation are therefore of great interest. Administration of packed red cells, fresh frozen plasma, and platelet concentrates is associated with volume loading, which is suspected to multiply the secondary brain damage, for example, by the development of an edema. In this respect, the administration of rFVIIa may develop into a new option associated with low-volume administration. CASE DESCRIPTIONS: We report on 5 neurosurgical patients to whom rFVIIa was given at doses of 51 to 202 microg/kg of body weight for the treatment of severe intraoperative bleeding (n = 3) or as prophylaxis of bleeding (n = 2). The operation was completed successfully in all patients after administration of rFVIIa, with stabilization of the coagulation status. CONCLUSION: Therefore, reported cases constitute an approach in treatment and prophylaxis of bleeding complications in neurosurgery. There are reports of thromboembolic events in use of rFVIIa, particularly in unlabeled use. But according to our findings and current literature, there is no evidence of higher risk of thromboembolic adverse events in treatment with rFVIIa. However, the number of patients presented does not allow any final assessment to be made as to whether the properties of rFVIIa are of particular benefit for neurosurgical patients. Further studies with appropriate study design are required to verify effects observed in this investigation.

Fracture of the occipital condyle caused by minor trauma in child.

We report a case of fractured occipital condyle caused by minor trauma accompanied by light pain on palpation at the lateral cervical trigonum. A 15-year-old boy complained of nuchal pain, particularly pain on palpation at the left lateral cervical trigonum in the absence of neurologic deficits after head deceleration trauma. Computed tomography demonstrated a unilateral nonluxated fracture of the occipital condyle. Owing to consequent immobilization by means of cervical orthosis, pain disappeared after the first 48 hours. Follow-up examination 4 weeks later showed no neurologic deficits. The boy had no severe impairment of movements at the cervical spine.

Induction of the photoaging-associated mitochondrial common deletion in vivo in normal human skin.

Mutations of mitochondrial (mt) DNA such as the 4977 base-pair large-scale deletion, also called common deletion, are increased in photoaged skin. Direct evidence for their induction by chronic exposure to ultraviolet (UV) radiation in vivo in human skin has remained elusive however. Furthermore, their fate after induction is unclear. Previously unirradiated skin of 52 normal human individuals was repetitively exposed to physiological doses of UVA light. Skin and blood specimens were investigated for the presence of mtDNA mutations employing semiquantitative nested PCR, as well as real-time PCR, after 2 weeks of UV exposure and the content of the common deletion was followed up for up to 16 mo after cessation of irradiation. As assessed by both methods, repetitive UV exposure led to an approximately 40% increase in the levels of the common deletion in normal human skin. The majority of deletions were detectable in the dermis also showing the biggest increase, whereas in the epidermis only residual levels and no increase were found. Nine individuals were examined up to 16 mo after cessation of UV exposure and some showed accumulation up to 32-fold. Thus, mtDNA mutations are induced in the human skin by repetitive UV exposure. In addition, these mutations seem to represent long-term in-vivo biomarkers for actinic damage in the human skin.