Clinical pilot study of transcranial direct current stimulation combined with Cognitive Emotional Training for medication resistant depression.

BACKGROUND: While the clinical results from transcranial direct current stimulation (tDCS) for the treatment of depression have been promising, antidepressant effects in patients with medication resistance have been suboptimal. There is therefore a need to further optimise tDCS for medication resistant patients. In this clinical pilot study we examined the feasibility, safety, and clinical efficacy of combining tDCS with a psychological intervention which targets dysfunctional circuitry related to emotion regulation in depression, Cognitive Emotional Training (CET). METHODS: tDCS was administered during CET three times a week for a total of 18 sessions over 6 weeks. Mood, cognition and emotion processing outcomes were examined at baseline and after 3 and 6 weeks of treatment. RESULTS: Twenty patients with medication resistant depression participated, of whom 17 were study completers. tDCS combined with CET was found to be feasible, safe, and associated with significant antidepressant efficacy at 6 weeks, with 41% of study completers showing treatment response (≥ 50% improvement in depression score). There were no significant cognitive enhancing effects with the exception of improved emotion recognition. Responders demonstrated superior recognition for the emotions fear and surprise at pre-treatment compared to non-responders, suggesting that better pre-treatment emotion recognition may be associated with antidepressant efficacy. LIMITATIONS: This was an open label study. CONCLUSIONS: tDCS combined with CET has potential as a novel method for optimising the antidepressant efficacy of tDCS in medication resistant patients. Future controlled studies are required to determine whether tDCS combined with CET has greater antidepressant efficacy compared to either intervention alone.

Improvement to the scanning electron microscope image adaptive Canny optimization colorization by pseudo-mapping.

An improvement to the previously proposed adaptive Canny optimization technique for scanning electron microscope image colorization is reported. The additional feature, called pseudo-mapping technique, is that the grayscale markings are temporarily mapped to a set of pre-defined pseudo-color map as a mean to instill color information for grayscale colors in chrominance channels. This allows the presence of grayscale markings to be identified; hence optimization colorization of grayscale colors is made possible. This additional feature enhances the flexibility of scanning electron microscope image colorization by providing wider range of possible color enhancement. Furthermore, the nature of this technique also allows users to adjust the luminance intensities of selected region from the original image within certain extent.

Clinical management and functional neuromonitoring in traumatic brain injury in children.

PURPOSE OF REVIEW: Traumatic brain injury is the main cause of childhood disability and death. In this review, we highlight recent original findings and emerging themes from published literature on children with serious traumatic brain injury. RECENT FINDINGS: We focus this review on lessons learned from our recent randomized clinical trial of hypothermia therapy in severe traumatic brain injury in children and on bedside neuromonitoring. We propose that integrating the measurement of biomarkers into clinical care as surrogate endpoints and as potential prognostic markers would allow us to evaluate earlier the effect of injury and clinical care in children after traumatic brain injury. Several methods are now more readily available to monitor cerebral physiology in children. These methods include indices evaluating the integrity of cerebral autoregulation, such as the pressure reactivity index derived from values obtained from intracranial pressure measurements, flow velocity measurements from transcranial Doppler ultrasonography or from cerebral oximetry. Other methods allow the evaluation of coma with the nonlinear analysis of electroencephalography or the evaluation of cerebral metabolism and cell death pathways with biomarkers from serum, cerebral spinal fluid, and cerebral microdialysis. SUMMARY: We suggest expanding clinical functional neuromonitoring to help clinicians understand the burden of exposure to physiological variables and response to therapies during intensive care in order to enhance the management of critically ill children with traumatic brain injury.

Effective performance of a new post-operative cardiac resuscitation simulation training scheme in the Paediatric Intensive Care Unit.

OBJECTIVE: This feasibility study aimed to describe and evaluate the effectiveness of a novel chest re-opening paediatric resuscitation scenario training scheme. METHODS: A novel scheme offering training on specialist skills required for post-operative cardiac patients such as chest re-opening and cardiac pacing via simulation was described. A prospective audit of the first 23 consecutive training sessions was conducted to assess the scheme's effectiveness. Parameters assessed included timing of chest re-opening or cardiac pacing orders, and any delays in carrying out these orders. RESULTS: The median time required for the medical team leader to order chest re-opening was 4 min. New medical leaders took significantly longer to order chest re-opening than experienced medical team leaders (P = 0.02, Mann-Whitney U test). The performance of the team-in-training deteriorated with the introduction of new members but was correctable with serial training. CONCLUSIONS: Effective simulation training integrating chest re-opening and cardiac pacing into standard paediatric resuscitation guidelines may be achieved without high fidelity simulation equipment.

Modulating effect of apolipoprotein E polymorphisms on secondary brain insult and outcome after childhood brain trauma.

OBJECTIVE: The aim of this study was to determine the relationship between apolipoprotein E (APO E) alleles, the amount of cerebral perfusion pressure (CPP) insult and outcome in children after brain trauma. MATERIALS AND METHODS: In a prospective two-centre case-control study, the APO E genotypes of 65 critically ill children admitted after brain trauma were correlated with age-related CPP insult quantification, conscious state at the time of discharge from intensive care and global outcome at 6 months post-injury. One hundred sixty healthy age- and sex-matched children were genotyped as controls. RESULTS: The CPP insult level among the e4 carriers with poor outcome was significantly less than the non-e4 carriers (p=0.03). Homozygotic e3 patients with good recovery did so despite having suffered nearly 26 times more CPP insult than those who were not e3 homzygous (p=0.02). CONCLUSION: Different APO E alleles may potentially affect cerebral ischaemic tolerance differently in children after brain trauma.

Specialist team retrieval of head injured patients: fact, fiction, or formula?

OBJECTIVE: This feasibility study aimed to determine the maximum theoretical distance the Edinburgh Paediatric Retrieval Team (EPRT) could travel to retrieve head injured children without additional delay in reaching definitive care. DESIGN: A prospective audit was conducted over 2 years to determine the current practice for paediatric head injury transfers (stabilisation, referral, and transfer time) undertaken by primary hospital staff, and the performance (mobilisation and travel time) of the EPRT. A novel formula was devised and used to determine the theoretical maximum radius within which the EPRT could reach a referring hospital during their stabilisation of head injured patients. MEASUREMENTS AND RESULTS: During the study period, 27 head injured patients were transferred to our unit by road and the EPRT conducted 194 road retrievals. The median stabilisation time for the head injured patients was 3.6 h. Median time to refer these patients to neurosurgical services was 1 h after presenting to primary hospitals. Median mobilisation time for EPRT was 1 h. Using our novel formula, 67 miles was the theoretical maximum radius within which the EPRT could reach a referring hospital during their stabilisation of head injured patients. CONCLUSIONS: Specialist team retrieval of paediatric head injury is a possibility, but not without significant organisational changes such as availability of second teams, early referral of patients and utilisation of the mobilisation time as a cancellation window. Our novel formula offers other teams a starting point to assess their own performance and to develop services.

Are head injury guidelines changing the outcome of head injured children? A regional investigation.

BACKGROUND: Secondary pathophysiological CPP insult is related to outcome after head injury, and improved management would be expected to reduce secondary brain insult. Paediatric head injury management guidelines have been published in recent years, by SIGN (2000), RCPCH (2001), NICE (June 2003), and jointly by Critical/Intensive Care Societies (C/ICS July 2003). We investigated whether outcome of children's head injury (and total burden of secondary CPP insult) has changed (1) annually; (2) before and after the introduction of any HI guidelines, and (3) following other service changes. METHODS: Seventy-six children (aged 1-14 years with severe HI) were admitted to the Edinburgh Regional Head Injury Service between 1989 and 2006, and dichotomised at various time points and compared in terms of: demographic factors, intracranial pressure (ICP), cerebral perfusion pressure (CPP) insults [e.g. age-banded pressure-time index (PTI)], and Glasgow Outcome Scale (GOS) score (assessed at 6 months post injury). FINDINGS: When dichotomised around the SIGN guidelines, there were no statistically significant differences between the two group's demography or in primary brain injury, but the outcomes were different (p = 0.03), with 6 vs 4 GOS1 (died), 2 vs 4 GOS3 (severely disabled), 5 vs 16 GOS4 (moderately disabled) and 23 vs 14 GOS5 (good recovery), when comparing before and after year 2000. GOS4 was significantly different (chi-square = 7.99, p < 0.007). There was a (non-significant) trend for the later years to have longer insult durations of ICP, hypertension, CPP, hypoxia, pyrexia, tachycardia and bradycardia, greater PTI for both CPP and ICP, and more CPP insults (p = 0.003). There was, however, significantly less CPP insult (p = 0.030) after the introduction of the more management-oriented C/ICS guidelines. CONCLUSIONS: The most recent paediatric HI guidelines appear to have reduced the burden of secondary insult, but more time is required to determine if this will be reflected in improved outcomes.

Critical thresholds of intracranial pressure and cerebral perfusion pressure related to age in paediatric head injury.

BACKGROUND: The principal strategy for managing head injury is to reduce the frequency and severity of secondary brain insults from intracranial pressure (ICP) and cerebral perfusion pressure (CPP), and hence improve outcome. Precise critical threshold levels have not been determined in head injured children. OBJECTIVE: To create a novel pressure-time index (PTI) measuring both duration and amplitude of insult, and then employ it to determine critical insult thresholds of ICP and CPP in children. METHODS: Prospective, observational, physiologically based study from Edinburgh and Newcastle, using patient monitored blood pressure, ICP, and CPP time series data. The PTI for ICP and CPP for 81 children, using theoretical values derived from physiological norms, was varied systematically to derive critical insult thresholds which delineate Glasgow outcome scale categories. RESULTS: The PTI for CPP had a very high predictive value for outcome (receiver operating characteristic analyses: area under curve = 0.957 and 0.890 for mortality and favourable outcome, respectively) and was more predictive than for ICP. Initial physiological values most accurately predicted favourable outcome. The CPP critical threshold values determined for children aged 2-6, 7-10, and 11-15 years were 48, 54, and 58 mm Hg. respectively. CONCLUSIONS: The PTI is the first substantive paediatric index of total ICP and CPP following head injury. The insult thresholds generated are identical to age related physiological values. Management guidelines for paediatric head injuries should take account of these CPP thresholds to titrate appropriate pressor therapy.

Quantification of secondary CPP insult severity in paediatric head injured patients using a pressure-time index.

This paper describes and validates a new Cumulative Pressure-Time Index (CPT) which takes into account both duration and degree of cerebral perfusion pressure (CPP) derangement and determines critical thresholds for CPP, in a paediatric head injury dataset. Sixty-six head-injured children, with invasive minute-to-minute intracranial pressure (ICP) and blood pressure monitoring, had their pre-set CPP derangement episodes (outside the normal range) identified in three childhood age-bands (2-6, 7-10, and 11-16 years) and global outcome assessed at six months post injury. The new cumulative pressure-time index more accurately predicted outcome than previously used summary measures and by varying the threshold CPP values, it was found that these physiological threshold values (< or = 48, < or = 52 and < or = 56 mmHg for 2-6, 7-10, and 11-16 years respectively) best predicted brain insult in terms of subsequent mortality and morbidity.

Inner calvarial erosion from traumatic subdural haematoma in infancy.

CASE REPORT: This is a report of a case of a subdural haematoma in infancy of possible non-accidental aetiology with raised pericerebral pressure, which we postulate has eroded the inner table of the cranial bones and resulted in leakage of marrow precursor cells into the extradural space. RESULT: Subdural tapping via the fontanelle has created a channel allowing subsequent ingress of nucleated red cell precursors into the subdural space. This addition to the subdural collection has prolonged its course necessitating subduro-peritoneal shunting.

Influence of aggregate pre-wetting and fly ash on mechanical properties of lightweight concrete.

This study has examined the mechanical properties of lightweight aggregate concrete with a density of 1800 kg/m3. The effects of the following parameters on the concrete properties have been analyzed: the pre-wetting time of the lightweight aggregate and the percentage of pulverized fly ash used as cementitious replacement material. The strength of the lightweight aggregate was found to be the primary factor controlling the strength of high-strength lightweight concrete. An increase in the cementitious content from 420 to 450 kg/m3 does not significantly increase the strength of lightweight aggregate concrete. The relationship between the flexural and compressive strength at 28 days can be represented by the equation fr=0.69/fck. The elastic modulus was found to be much lower than that of normal weight concrete, ranging from 15.0 to 20.3 GPa. The addition of PFA increases the slump and density of lightweight aggregate concrete.

Cerebral atrophy following shaken impact syndrome and other non-accidental head injury (NAHI).

PURPOSE OF THE STUDY: To determine the frequency of cerebral atrophy and microcephaly in a group of children with sequential MRI brain scans after surviving a non-accidental head injury (n = 16). METHODS: Serial head circumference measurements (OFC) were extracted and plotted on standard growth charts for each child retrospectively to determine the frequency of secondary microcephaly. Cerebral atrophy was diagnosed and quantified by measurement of the ventricular/cortical ratio on coronal images of the sequential scans. RESULTS: Acquired microcephaly was found in 15 children (93.8%) over a median follow-up period of 67.93 weeks. There was a significant reduction in the median Z-score for the OFC at the most recent follow-up when compared with that at presentation (p < 0.001, Wilcoxon Signed Rank Test). Cerebral atrophy was found to be the cause of the microcephaly in eight of the 15 children and was evident as early as 9 days after presentation. CONCLUSION: A large proportion of the cohort (93.8%) develops acquired microcephaly after an inflicted head injury and cerebral atrophy is responsible in half of these cases.

Graphical display of variability and inter-relationships of pressure signals in children with traumatic brain injury.

A prospective observational study was undertaken to examine time series ICU data of pressure variables (mean arterial pressure (MAP), intracranial pressure (ICP) and cerebral perfusion pressure (CPP)) and relate their variability (SD) to outcome, together with simple graphical displays which could be useful at the ICU bedspace. Forty-three children (aged < 1-15 years) were admitted to the intensive care unit for Regional Neurosurgical Service, Edinburgh, following traumatic brain injury (TBI). The standard deviations from 221,291 validated pressure data measurements (representing three variables) were calculated for the duration of ICP monitoring (and in 48 h epochs from the time of injury). Data were displayed on polygraphs, and several well-defined 'patterns' were described. The standard deviations of MAP, ICP and CPP for the total duration of monitoring were found to be significantly related to survival (p = 0.003, <0.001 and 0.005, respectively), while the SD of ICP alone was strongly related to global recovery (p = 0.008) in the first 48 h post-injury. Patterns in 104 epochs (each of 48 h) were identified. Ninety-two were of the type I (MAP > CPP > ICP) pattern and 12 were of the non-type I pattern. Glasgow Outcome Scale scores at 12 months were significantly related to the dichotomized pattern type (Fisher's exact test p < 0.001 for both alive versus dead and independent versus dependent outcomes). Only one patient with type I pattern died in this series. While variability of ICP during the first 48 h post-injury is predictive of the outcome, the pattern behaviour of three pressure signals gives useful outcome prediction information throughout monitoring. These displays may help interpret some of the plethora of data produced at the bedside.

Long-term risks and benefits of a separate CSF access device with ventriculoperitoneal shunting in childhood hydrocephalus.

To determine the long-term risks and benefits of a separate CSF reservoir in the management of 52 children (23 males, 29 females) with shunted hydrocephalus, a retrospective study was performed comparing the use and complications after separate reservoir insertion, with a prereservoir control period. Median age at first shunt insertion was 1 month and median age at reservoir insertion was 2 years 6 months. Median follow-up for shunt with the additional reservoir was 19 years 1 month. There was no mortality due to shunt failure nor CNS infection, and there were significantly fewer episodes of ventriculitis (p < 0.01) and shunt blockage (p < 0.0001) compared with the prereservoir period. There was no hemiplegia, epilepsy, visual, nor cognitive loss from the additional reservoir. The reservoir was used for access in 344 attendances (mean 6.62 attendances per patient) for diagnosis or treatment of raised pressure or CNS infection. It was concluded that a separate CSF reservoir is useful in the long-term management of patients with shunted hydrocephalus and is without mortality or significant increased morbidity.

Bronchial Rn dose survey for residences.

The bronchial dosimeter for Rn progeny proposed by Yu and Guan in 1998 was employed to survey the bronchial dose from Rn progeny in 30 residences in Hong Kong. An average bronchial deposition fraction of Rn progeny was obtained as 0.0334, which gave an average dose conversion factor (DCF) of 8.5 mSv WLM-1. The mean values of potential alpha energy concentration (PAEC) deposited in the tracheobronchial region (PAECT-B), total PAEC in air (PAECT), annual effective dose (E), concentration of Rn gas (RC) and annual dose conversion factor (ADCF) for all the residential sites combined were 0.11 +/- 0.05, 3.1 +/- 1.4 mWL, 1.2 +/- 0.5 mSv yr-1, 23 +/- 10 Bq m-3 and 0.055 +/- 0.020 (mSv yr-1 per Bqm-3), respectively, with air-conditioned sites (AC sites) and non-AC sites having significantly different mean ADCF values. The indoor relative humidity affected PAECT and RC with high confidence levels (> 95%).

Ionic mechanisms for the antiarrhythmic action of cinnamophilin in rat heart.

We investigated the electrophysiological effect and antiarrhythmic potential of cinnamophilin (Cinn), a thromboxane A(2) antagonist isolated from Cinnamomum philippinense, on rat cardiac tissues. Action potential and ionic currents in single rat ventricular cells were examined by current clamp or voltage clamp in a whole-cell configuration. In 9 episodes of ischemia-reperfusion arrhythmia, 10 microM Cinn converted 6 of them to normal sinus rhythm. Cinn suppressed the maximal rate of rise of the action potential upstroke (V(max)) and prolonged the action potential duration at 50% repolarization (APD(50)). Voltage clamp study showed that the suppression of V(max) by Cinn was associated with an inhibition of sodium inward current (I(Na), IC(50) = 10.0 +/- 0.4 microM). At 30 microM, V(1/2) for the steady-state inactivation curve of I(Na) was shifted from -84.1 +/- 0.2 to -93.0 +/- 0.5 mV. Cinn also reduced calcium inward current (I(Ca)) dose-dependently with an IC(50) value of 9.5 +/- 0.3 microM. Cinn (10 microM) reduced the I(Ca) with a negative shift of V(1/2) for the steady-state inactivation curve of I(Ca) from -32.2 +/- 0.3 to -50.7 +/- 0.4 mV. The prolongation of APD(50) was associated with an inhibition of the integral of potassium outward current with IC(50) values between 4.8 and 7.1 microM. At 10 microM, Cinn reduced I(Na) without a negative shift of its voltage-dependent steady-state inactivation curves. The inhibition of transient outward current (I(to)) by Cinn (3-30 microM) was associated with an acceleration of its time constant of inactivation and negative shift of its potential-dependent steady-state inactivation curves. The equilibrium dissociation constant (K(d)) of Cinn to inhibit open state I(to) channels, as calculated from the time constant of developing block, was 18.3 microM. The time constant of recovery of I(to) from inactivation state was unaffected by Cinn. The rate constant for the relief from the depolarization-dependent block of I(to) was calculated to be 23. 9 ms. As compared with its effect on I(to), Cinn exerted about half the potency to block I(Na) and I(Ca). These results indicate that the inhibition of I(Na), I(Ca) and I(to) may contribute to the antiarrhythmic activity of Cinn against ischemia-reperfusion arrhythmia.

Prognostic significance of DNA flow cytometric analysis in patients with nasopharyngeal carcinoma.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a prevalent malignant tumor among Southern Chinese. Previously, the authors described the prognostic significance of a serum antibody assay to a recombinant Epstein-Barr virus Bam HI-Z replication activator protein (ZEBRA) in NPC patients with long term follow-up. In this study, the authors further reported the use of DNA flow cytometry (DNA-FCM) as an additional technique for determining the prognosis of NPC patients in the same series. METHODS: One hundred and forty-three archival biopsies from 110 NPC patients were deparaffinized and subjected to DNA-FCM analysis. DNA ploidy state and various proliferative indices (PI) of the tumors were correlated with patient survival and frequency of recurrence. RESULTS: Among the biopsies analyzed, 119 were histologically positive NPC and 24 were negative. Fifty-one tumor biopsies that fulfilled the guideline criteria of the DNA Cytometry Consensus Conference were correlated with the clinical manifestations of the patients. Among them, 43 tumors (84%) were DNA diploid and 8 (16%) were aneuploid. Two PI, S-phase fraction (SPF) and proliferation fraction (PF), appear to be potentially useful prognostic indicators. For example, PF in patients who developed locoregional recurrence (15.1%) and distant recurrence (16.4%) after radiation therapy both were significantly higher than PF in patients who were in complete remission (8.2%) (P = 0.0005 and P = 0.004, respectively). Significant differences in SPF between patients with distant recurrence (10.6%) and those in remission (5.7%) also was found (P = 0.005). Using Kaplan-Meier analysis, patients with high PF, high SPF, and aneuploid tumors had significantly poorer 12-year survival rates (35%, 26%, and 28%, respectively) than those patients with low PF, low SPF, and diploid tumors (77%, 67%, and 59%, respectively) (P < 0.0009, P < 0.004, and P < 0.01, respectively). CONCLUSIONS: Determination of tumor PI and DNA ploidy state by DNA-FCM at diagnosis of NPC can be potentially useful in selecting a poor prognostic subgroup of NPC patients. These parameters may enable oncologists to plan for more stringent treatment strategies such as hyperfractionated and accelerated radiation therapy or concomitant chemoradiotherapy for these patients.