Small-fibre neuropathy in a patient with dermatomyositis and severe scalp pruritus.

Dermatomyositis (DM) is commonly associated with scalp pruritus that can be severe. In addition, significant crawling and burning sensations have been reported in these cases. The aetiology of these scalp sensations in the context of DM is not fully understood. We report a 42-year-old female with treatment-resistant DM and structural changes in scalp epidermal and dermal nerve fibres. The patient presented with characteristic skin manifestations (Gottron's papules and poikiloderma), severely pruritic scalp, intermittent muscle weakness on neurological exam with electrodiagnostically confirmed myositis, and joint pain. Structural changes in scalp epidermal and dermal nerve fibres were discovered in a skin biopsy, suggesting that small-fibre neuropathy associated with scalp pruritus may be a manifestation of the DM syndrome. Further clinical experience combined with selective skin biopsy in patients with DM and symptomatic scalp will help determine the frequency of coexistent small nerve fibre involvement. Based on our limited findings, we suggest that pruritus in DM may be associated with abnormal epidermal and dermal nerve fibre structure.

A computational workflow for designing silicon donor qubits.

Developing devices that can reliably and accurately demonstrate the principles of superposition and entanglement is an on-going challenge for the quantum computing community. Modeling and simulation offer attractive means of testing early device designs and establishing expectations for operational performance. However, the complex integrated material systems required by quantum device designs are not captured by any single existing computational modeling method. We examine the development and analysis of a multi-staged computational workflow that can be used to design and characterize silicon donor qubit systems with modeling and simulation. Our approach integrates quantum chemistry calculations with electrostatic field solvers to perform detailed simulations of a phosphorus dopant in silicon. We show how atomistic details can be synthesized into an operational model for the logical gates that define quantum computation in this particular technology. The resulting computational workflow realizes a design tool for silicon donor qubits that can help verify and validate current and near-term experimental devices.

Photophysics and ex vivo biodistribution of ß-cyclodextrin-meso-tetra(m-hydroxyphenyl)porphyrin conjugate for biomedical applications.

Low aqueous solubility of porphyrin-based photosensitizers hampers their clinical use in photodynamic therapy because of complex delivery. In this study, we explore meso-tetra(m-hydroxyphenyl)-21,23H-porphyrin (mTHPP), a potent photosensitizer, covalently attached to ß-cyclodextrin (CD-mTHPP) with a focus on topical delivery and cellular uptake. The photophysical properties of CD-mTHPP were examined using steady-state fluorescence and lifetime measurements verifying increased aqueous solubility. Confocal and fluorescence lifetime imaging microscopy on human squamous carcinoma cells (A431) evidenced a cytoplasmic uptake of CD-mTHPP in predominantly monomeric form. CD-mTHPP was also delivered to human skin ex vivo and the skin penetration was assessed using two-photon fluorescence microscopy. The results indicated that CD-mTHPP exhibits improved skin distribution compared to mTHPP alone using aqueous vehicles. Thus the CD-mTHPP conjugate demonstrates improved biodistribution ex vivo compared to mTHPP and is a promising multimodal system for photodynamic therapy.

Vertically aligned carbon nanofiber as nano-neuron interface for monitoring neural function.

Neural chips, which are capable of simultaneous multisite neural recording and stimulation, have been used to detect and modulate neural activity for almost thirty years. As neural interfaces, neural chips provide dynamic functional information for neural decoding and neural control. By improving sensitivity and spatial resolution, nano-scale electrodes may revolutionize neural detection and modulation at cellular and molecular levels as nano-neuron interfaces. We developed a carbon-nanofiber neural chip with lithographically defined arrays of vertically aligned carbon nanofiber electrodes and demonstrated its capability of both stimulating and monitoring electrophysiological signals from brain tissues in vitro and monitoring dynamic information of neuroplasticity. This novel nano-neuron interface may potentially serve as a precise, informative, biocompatible, and dual-mode neural interface for monitoring of both neuroelectrical and neurochemical activity at the single-cell level and even inside the cell. FROM THE CLINICAL EDITOR: The authors demonstrate the utility of a neural chip with lithographically defined arrays of vertically aligned carbon nanofiber electrodes. The new device can be used to stimulate and/or monitor signals from brain tissue in vitro and for monitoring dynamic information of neuroplasticity both intracellularly and at the single cell level including neuroelectrical and neurochemical activities.

Lumateperone-mediated effects on prefrontal glutamatergic receptor-mediated neurotransmission: A dopamine D1 receptor dependent mechanism.

Lumateperone is a novel drug approved for the treatment of schizophrenia in adults and depressive episodes associated with bipolar depression in adults, as monotherapy and as adjunctive therapy with lithium or valproate treatment in the United States. Lumateperone simultaneously modulates key neurotransmitters, such as serotonin, dopamine, and glutamate, implicated in serious mental illness. In patients with schizophrenia, lumateperone was shown to improve positive symptoms along with negative and depressive symptoms, while also enhancing prosocial behavior. Moreover, in patients with bipolar I or II disorder, lumateperone improved depressive symptoms as well. To further understand the mechanisms related to lumateperone's clinical response, the aim of this study was to investigate the effect of lumateperone on dopaminergic- and glutamatergic signaling in the rat medial prefrontal cortex (mPFC). We used the conditioned avoidance response (CAR) test to determine the antipsychotic-like effect of lumateperone, electrophysiology in vitro to study lumateperone's effects on NMDA- and AMPA-induced currents in the mPFC, and the neurochemical techniques microdialysis and amperometry to measure dopamine- and glutamate release in the rat mPFC. Our results demonstrate that lumateperone; i) significantly suppressed CAR in rats, indicating an antipsychotic-like effect, ii) facilitated NMDA and AMPA receptor-mediated currents in the mPFC, in a dopamine D1-dependent manner, and iii) significantly increased dopamine and glutamate release in the rat mPFC. To the extent that these findings can be translated to humans, the ability of lumateperone to activate these pathways may contribute to its demonstrated effectiveness in safely improving symptoms related to neuropsychiatric disorder including mood alterations.

Metabolically stabilized long-circulating PEGylated polyacridine peptide polyplexes mediate hydrodynamically stimulated gene expression in liver.

A novel class of PEGylated polyacridine peptides was developed that mediate potent stimulated gene transfer in the liver of mice. Polyacridine peptides, (Acr-X)(n)-Cys-polyethylene glycol (PEG), possessing 2-6 repeats of Lys-acridine (Acr) spaced by either Lys, Arg, Leu or Glu, were Cys derivatized with PEG (PEG(5000 kDa)) and evaluated as in vivo gene transfer agents. An optimal peptide of (Acr-Lys)(6)-Cys-PEG was able to bind to plasmid DNA (pGL3) with high affinity by polyintercalation, stabilize DNA from metabolism by DNAse and extend the pharmacokinetic half-life of DNA in the circulation for up to 2 h. A tail vein dose of PEGylated polyacridine peptide pGL3 polyplexes (1 µg in 50 µl), followed by a stimulatory hydrodynamic dose of normal saline at times ranging from 5 to 60 min post-DNA administration, led to a high level of luciferase expression in the liver, equivalent to levels mediated by direct hydrodynamic dosing of 1 µg of pGL3. The results establish the unique properties of PEGylated polyacridine peptides as a new and promising class of gene delivery peptides that facilitate reversible binding to plasmid DNA, protecting it from DNase in vivo resulting in an extended circulatory half-life, and release of transfection-competent DNA into the liver to mediate a high-level of gene expression upon hydrodynamic boost.

Accounting for the association between childhood maltreatment and alcohol-use disorders in males: a twin study.

BACKGROUND: An association between childhood maltreatment and subsequent alcohol abuse and/or dependence (AAD) has been found in multiple studies of females. Less is known about the association between childhood maltreatment and AAD among males, and the mechanisms that underlie this association in either gender. One explanation is that childhood maltreatment increases risk for AAD. An alternative explanation is that the same genetic or environmental factors that increase a child's risk for being maltreated also contribute to risk for AAD in adulthood. METHOD: Lifetime diagnosis of AAD was assessed using structured clinical interviews in a sample of 3527 male participants aged 19-56 years from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders. The sources of childhood maltreatment-AAD association were estimated using both a matched case-control analysis of twin pairs discordant for childhood maltreatment and bivariate twin modeling. RESULTS: Approximately 9% of participants reported childhood maltreatment, defined as serious neglect, molestation, or physical abuse occurring before the age of 15 years. Those who experienced childhood maltreatment were 1.74 times as likely to meet AAD criteria compared with males who did not experience childhood maltreatment. The childhood maltreatment-AAD association largely reflected environmental factors in common to members of twin pairs. Additional exploratory analyses provided evidence that AAD risk associated with childhood maltreatment was significantly attenuated after adjusting for measured family-level risk factors. CONCLUSIONS: Males who experienced childhood maltreatment had an increased risk for AAD. Our results suggest that the childhood maltreatment-AAD association is attributable to broader environmental adversity shared between twins.

Heart rate variability (HRV) in adolescent females with anxiety disorders and major depressive disorder.

AIM: The aim of this study was to investigate heart rate variability (HRV) in a clinical sample of female adolescents with anxiety disorders (AD) and/or major depressive disorder (MDD) compared with healthy controls and to assess the effect of selective serotonin reuptake inhibitors (SSRI) on HRV. METHODS: Heart rate variability was measured in adolescent female psychiatric patients with AD and/or MDD (n = 69), mean age 16.8 years (range: 14.5-18.4), from 13 out-patient clinics and in healthy controls (n = 65), mean age 16.5 years (range: 15.9-17.7). HRV was registered in the sitting position during 4 min with no interventions. RESULTS: Logarithmically transformed high frequency HRV (HF), low frequency HRV (LF) and standard deviation of inter beat intervals (SDNN) were lower in the clinical sample compared with the controls (Cohen's d for HF = 0.57, LF = 0.55, SDNN = 0.60). This was not explained by body mass index, blood pressure or physical activity. Medication with SSRI explained 15.5% of the total variance of HF, 3.0% of LF and 6.5% of SDNN. CONCLUSIONS: Adolescent female psychiatric patients with AD and/or MDD show reduced HRV compared with healthy controls. Medication with SSRI explained a part of this difference.

Mechanistic studies of ethanol's interaction with the mesolimbic dopamine reward system.

Alcoholism is a chronic recurring brain disorder causing the afflicted a multitude of social and health problems and enormous costs to society. The psychosocial and pharmacological treatment options available have but small to moderate effect sizes, underlining the great need for new effective remedies. Alcohol like all other drugs of abuse acutely activates the mesolimbic dopamine system and, upon chronic administration, produces functional alterations of this important part of the brain reward system. Available data suggests that the mesolimbic dopamine system is involved both in the positive and negative reinforcing effects of ethanol. It hence becomes imperative to understand how ethanol interferes with this system. Increased knowledge about these mechanisms may open up for new targets for pharmacotherapies. We have investigated the tentative involvement of cys-loop ligand-gated ion-channels, which ethanol is known to interact with in relevant concentrations. Our data indicate that a neuronal circuitry involving glycine receptors in the nucleus accumbens, and, secondarily, nicotinic acetylcholine receptors in the ventral tegmental area is involved in the mesolimbic dopamine activating and reinforcing effects of ethanol. Manipulations of both these receptor populations have the potential to modulate ethanol consumption. The proposed neurocircuitry, has implications for understanding ethanol conditioned dopamine activation, chronic effects of ethanol on the mesolimbic dopamine system and the overall role/importance of dopamine and the nucleus accumbens for the reinforcing effects of ethanol. Computational neuroscience in conjunction with further emperical observations is likely to facilitate this process.

Bioavailability of aminolaevulinic acid and methylaminolaevulinate in basal cell carcinomas: a perfusion study using microdialysis in vivo.

BACKGROUND: Photodynamic therapy is becoming a popular treatment for superficial nonmelanoma precancerous and cancerous lesions, showing excellent cosmetic results. Nevertheless, the reported cure rates vary and the transdermal penetration of drugs has been discussed as a limiting factor, particularly for treatment of nodular basal cell carcinoma (BCC). OBJECTIVES: To investigate the transdermal penetration of aminolaevulinic acid (ALA) and methylaminolaevulinate (MAL) in BCC in vivo using a microdialysis technique. The different prodrugs were compared and the effect of curettage was studied. METHODS: Twenty patients with 27 histologically verified BCCs (13 superficial, 14 nodular) were included. All lesions were located at the front of the body (head and face excluded). The first 10 patients included were treated with MAL (13 BCCs), and the following 10 patients with ALA (14 BCCs). A light curettage was performed on every second lesion (curettage, n = 13; noncurettage, n = 14). Microdialysis catheters were inserted into the tumours at tissue depths varying from 0.4 to 1.9 mm. Dialysates were collected at 15-30-min intervals for 4 h and the interstitial concentrations of MAL and ALA were determined using high-performance liquid chromatography. RESULTS: No significant difference in interstitial drug concentration was observed between lesions treated with ALA or MAL during the 4-h measurement period. However, for the lesions with deeper catheter locations, i.e. at or below 1 mm (n = 11), drug concentrations above the detection limit were obtained in only six lesions. All but one BCC with superficial catheter location, i.e. < 1 mm (n = 16), exhibited detectable drug concentration (P = 0.026). The interstitial peak concentrations were reached within 90 min in 23 of the 27 BCCs, but were not found to be correlated with the depth of the catheters. No difference was found when comparing superficial and nodular BCCs, and the effect of curettage was found to be negligible. CONCLUSIONS: The results imply that there is no significant difference in transdermal penetration of ALA and MAL in tumour tissue. Detectable levels of drug were not obtained in almost 50% of the lesions where catheters were situated 1-1.9 mm in the lesion. Curettage was not found to affect the interstitial concentration, indicating that penetration of drug indeed might be a problem when treating BCCs thicker than 1 mm.

Nerve blocks provide effective pain relief during topical photodynamic therapy for extensive facial actinic keratoses.

BACKGROUND: Photodynamic therapy (PDT) is a first-line therapeutic option for skin areas with multiple actinic keratoses (AKs). Its main drawback is the pain perceived during the irradiative phase, especially when treating field cancerization in the facial area. Effective pain-relieving strategies are needed. AIM: To determine the effectiveness of peripheral nerve blocks in achieving pain relief during PDT for extensive facial AKs. METHODS: In total, 16 patients with symmetrically distributed facial AKs, mainly on the forehead, were enrolled in the study. Nerve blocks were applied unilaterally, and the nonanaesthetized side of the treatment area served as control. Maximum pain during PDT was evaluated using a visual analogue scale (VAS). Pain experienced after PDT was evaluated by telephone interview within 2 weeks of treatment. Cure rates were assessed at follow-up at least 4 weeks after treatment. RESULTS: Pain was significantly reduced on the anaesthetized side (P < 10(-8)). The mean +/- SEM VAS score on the blocked side of the face was 1.3 +/- 0.3 compared with 7.5 +/- 0.5 on the nonanaesthetized side. Pain relief persisted 1-2 h after PDT. The nerve block was generally not experienced as painful (14/16 patients). Almost all patients (15/16 patients) would like to receive nerve blocks bilaterally if future PDT were needed. Excellent clinical results were observed in all patients after 4-20 weeks. CONCLUSION: Nerve blocks provide efficient pain relief during PDT when treating patients with field cancerization of the forehead. Nerve blocks were not found to affect the clinical outcome of PDT, and were generally well tolerated by the patients.

Change in surface hardness of enamel by a cola drink and a CPP-ACP paste.

OBJECTIVES: This in vitro study used surface microhardness to evaluate whether a paste containing casein phosphopeptide amorphous calcium phosphate (CPP-ACP) can reharden tooth enamel softened by a cola drink, and how different saliva-substitute solutions affect the enamel hardness. METHODS: Twenty-four bovine incisors, each tooth consisting of treatment and control halves, were immersed in a cola drink (Coke) for 8 min, then placed under a 0.4 mL/min drip with various saliva-substitute solutions. The saliva-substitute solutions were: saliva-like solution (SLS) with 1 ppm fluoride, SLS without fluoride, and Biotene mouthwash. CPP-ACP paste was applied to the treatment halves for 3 min at 0, 8, 24, and 36 h. Knoop microhardness measurements were performed at baseline, after the cola drink immersion, and after 24 and 48 h contact with saliva-substitute solution. RESULTS: Enamel hardness significantly decreased after immersion in cola drink (ANOVA, p<0.05). After contact with saliva-like solutions for 48 h, those treated with CPP-ACP paste were significantly harder than those untreated regardless of the presence of 1 ppm fluoride in the saliva-like solution (ANOVA, p<0.05). Biotene mouthwash significantly softened the enamel surface (ANOVA, p<0.05). Two-way ANOVA showed significant effects of the CPP-ACP paste application and types of saliva-substitute solutions on the changes in surface hardness of the softened enamel at a significance level of 0.05. CONCLUSION: The application of CPP-ACP paste with continuous replenishment of saliva-like solution for 48 h significantly hardened enamel softened by a cola drink. Biotene mouthwash softened enamel surface after 48 h contact.

Characterization of a reversible thermally-actuated polymer-valve: A potential dynamic treatment for congenital diaphragmatic hernia.

BACKGROUND: Congenital diaphragmatic hernia (CDH) is a fetal defect comprising an incomplete diaphragm and the herniation of abdominal organs into the chest cavity that interfere with fetal pulmonary development. Though the most promising treatment for CDH is via interventional fetoscopic tracheal occlusion (TO) surgery in-utero, it has produced mixed results due to the static nature of the inserted occlusion. We hypothesize that a suitable noninvasively-actuatable, cyclic-release tracheal occlusion device can be developed to enable dynamic tracheal occlusion (dTO) implementation. OBJECTIVE: To conduct an in-vitro proof-of-concept investigation of the construction of thermo-responsive polymer valves designed for targeted activation within a physiologically realizable temperature range as a first step towards potential development of a noninvasively-actuatable implantable device to facilitate dynamic tracheal occlusion (dTO) therapy. METHODS: Six thermo-responsive polymer valves, with a critical solution temperature slightly higher than normal physiological body temperature of 37°C, were fabricated using a copolymer of n-isopropylacrylamide (NIPAM) and dimethylacrylamide (DMAA). Three of the valves underwent ethylene oxide (EtO) sterilization while the other three served as controls for EtO-processing compatibility testing. Thermal response actuation of the valves and their steady-state flow performances were evaluated using water and caprine amniotic fluid. RESULTS: All six valves consisting of 0.3-mole fraction of DMAA were tested for thermal actuation of caprine amniotic fluid flow at temperatures ranging from 30-44°C. They all exhibited initiation of valve actuation opening at ~40°C with full completion at ~44°C. The overall average coefficient of variation (CV) for the day-to-day flow performance of the valves tested was less than 12%. Based on a Student t-test, there was no significant difference in the operational characteristics for the EtO processed versus the non-EtO processed valves tested. CONCLUSIONS: We successfully fabricated and demonstrated physiological realizable temperature range operation of thermo-responsive polymer valves in-vitro and their suitability for standard EtO sterilization processing, a prerequisite for future in-vivo surgical implantation testing.

In vivo performance of a visible wavelength optical sensor for monitoring intestinal perfusion and oxygenation.

Traumatic injury resulting in hemorrhage is a prevalent cause of death worldwide. The current standard of care for trauma patients is to restore hemostasis by controlling bleeding and administering intravenous volume resuscitation. Adequate resuscitation to restore tissue blood flow and oxygenation is critical within the first hours following admission to assess severity and avoid complications. However, current clinical methods for guiding resuscitation are not sensitive or specific enough to adequately understand the patient condition. To better address the shortcomings of the current methods, an approach to monitor intestinal perfusion and oxygenation using a multiwavelength (470, 560, and 630 nm) optical sensor has been developed based on photoplethysmography and reflectance spectroscopy. Specifically, two sensors were developed using three wavelengths to measure relative changes in the small intestine. Using vessel occlusion, systemic changes in oxygenation input, and induction of hemorrhagic shock, the capabilities and sensitivity of the sensor were explored in vivo. Pulsatile and nonpulsatile components of the red, blue, and green wavelength signals were analyzed for all three protocols (occlusion, systemic oxygenation changes, and shock) and were shown to differentiate perfusion and oxygenation changes in the jejunum. The blue and green signals produced better correlation to perfusion changes during occlusion and shock, while the red and blue signals, using a new correlation algorithm, produced better data for assessing changes in oxygenation induced both systemically and locally during shock. The conventional modulation ratio method was found to be an ineffective measure of oxygenation in the intestine due to noise and an algorithm was developed based on the Pearson correlation coefficient. The method utilized the difference in phase between two different wavelength signals to assess oxygen content. A combination of measures from the three wavelengths provided verification of oxygenation and perfusion states, and showed promise for the development of a clinical monitor.

Heart rate variability in patients with untreated epilepsy.

BACKGROUND: Several studies have reported reduced heart rate variability (HRV) in patients with chronic epilepsy under treatment with antiepileptic drugs. This impairment in cardiac autonomic control might be of relevance in relation to the risk of sudden unexpected death in patients with chronic refractory epilepsy. Little information is, however, available on HRV in untreated patients with newly diagnosed epilepsy. METHODS: We used spectral analysis to assess HRV based on 24h ambulatory EKG recordings in 22 consecutive untreated patients with epilepsy (15 with localization-related, 4 with generalized idiopathic and 3 with undetermined epilepsy). The HRV in these patients was compared with 22 age and sex matched healthy controls. RESULTS: When analysing the full 24h recordings, there were no significant difference between the patients and the controls in any of the analyzed measures of HRV: standard deviation of RR-intervals (P=0.191), total power (P=0.170), very low frequency power (P=0.329), low frequency power (LF) (P=0.161), high frequency power (HF) (P=0.186) and the LF/HF ratio (P=0.472). The results were very similar for daytime and nighttime recordings. CONCLUSION: Our results suggest that there is no major effect of epilepsy as such on HRV in patients with untreated epilepsy. It should be emphasized that this study assessed newly diagnosed patients and that the results may not be applicable to patients with chronic epilepsy.

In-silico and in-vitro investigation of a photonic monitor for intestinal perfusion and oxygenation.

The quantification of visceral organ oxygenation after trauma-related systemic hypovolemia and shock is critical to enable effective resuscitation. In this work, a photoplethysmography-based (PPG) sensor was specifically designed for probing the perfusion and oxygenation condition of intestinal tissue with the ultimate goal to monitor patients post trauma to guide resuscitation. Through Monte Carlo modeling, suitable optofluidic phantoms were determined, the wavelength and separation distance for the sensor was optimized, and sensor performance for the quantification of tissue perfusion and oxygenation was tested on the in-vitro phantom. In particular, the Monte Carlo simulated both a standard block three-layer model and a more realistic model including villi. Measurements were collected on the designed three layer optofluidic phantom and the results taken with the small form factor PPG device showed a marked improvement when using shorter visible wavelengths over the more conventional longer visible wavelengths. Overall, in this work a Monte Carlo model was developed, an optofluidic phantom was built, and a small form factor PPG sensor was developed and characterized using the phantom for perfusion and oxygenation over the visible wavelength range. The results show promise that this small form factor PPG sensor could be used as a future guide to shock-related resuscitation.

Naltrexone modulates dopamine release following chronic, but not acute amphetamine administration: a translational study.

The opioid antagonist naltrexone has been shown to attenuate the subjective effects of amphetamine. However, the mechanisms behind this modulatory effect are currently unknown. We hypothesized that naltrexone would diminish the striatal dopamine release induced by amphetamine, which is considered an important mechanism behind many of its stimulant properties. We used positron emission tomography and the dopamine D2-receptor radioligand [11C]raclopride in healthy subjects to study the dopaminergic effects of an amphetamine injection after pretreatment with naltrexone or placebo. In a rat model, we used microdialysis to study the modulatory effects of naltrexone on dopamine levels after acute and chronic amphetamine exposure. In healthy humans, naltrexone attenuated the subjective effects of amphetamine, confirming our previous results. Amphetamine produced a significant reduction in striatal radioligand binding, indicating increased levels of endogenous dopamine. However, there was no statistically significant effect of naltrexone on dopamine release. The same pattern was observed in rats, where an acute injection of amphetamine caused a significant rise in striatal dopamine levels, with no effect of naltrexone pretreatment. However, in a chronic model, naltrexone significantly attenuated the dopamine release caused by reinstatement of amphetamine. Collectively, these data suggest that the opioid system becomes engaged during the more chronic phase of drug use, evidenced by the modulatory effect of naltrexone on dopamine release following chronic amphetamine administration. The importance of opioid-dopamine interactions in the reinforcing and addictive effects of amphetamine is highlighted by the present findings and may help to facilitate medication development in the field of stimulant dependence.

Resident neuroelectrochemical interfacing using carbon nanofiber arrays.

Carbon nanofiber electrode architectures are used to provide for long-term, neuroelectroanalytical measurements of the dynamic processes of intercellular communication between excitable cells. Individually addressed, vertically aligned carbon nanofibers are incorporated into multielement electrode arrays upon which excitable cell matrixes of both neuronal-like derived cell lines (rat pheochromocytoma, PC-12) and primary cells (dissociated cells from embryonic rat hippocampus) are cultured over extended periods (days to weeks). Electrode arrays are characterized with respect to their response to easily oxidized neurotransmitters, including dopamine, norepinephrine, and 5-hydroxytyramide. Electroanalysis at discrete electrodes following long-term cell culture demonstrates that this platform remains responsive for the detection of easily oxidized species generated by the cultured cells. Preliminary data also suggests that quantal release of easily oxidized transmitters can be observed at nanofiber electrodes following direct culture and differentiation on the arrays for periods of at least 16 days.

No apparent effect of surgery for temporal lobe epilepsy on heart rate variability.

BACKGROUND: Impaired cardiac autonomic function may contribute to the risk of sudden unexpected death in epilepsy (SUDEP). Clinical observations indicate that successful epilepsy surgery is associated with a reduced risk of SUDEP. However, in a previous study we found impaired cardiac control pre-surgically in patients with poor outcome of surgery, indicating an a priori lower risk in responders to epilepsy surgery. We have now examined the effect of surgery on cardiac autonomic control in the same patients. METHODS: We used 24 h EKG recordings to assess heart rate variability (HRV) by spectral analysis in 21 consecutive patients after temporal lobe epilepsy surgery. The HRV was compared with healthy controls, with pre-surgical HRV in the same patients, and analyzed in relation to seizure control 1 year after surgery. RESULTS: The patients with poor outcome after surgery had significantly lower SD of RR-intervals, total power, very low frequency power and low frequency power than matched healthy controls. The patients with favorable outcome did not differ from the controls, and the postoperative HRV was not different from HRV before surgery in any of the patient groups. CONCLUSION: We could not demonstrate any effect on HRV of temporal lobe epilepsy surgery in these patients. The observed lower HRV in the poor outcome group was present already before epilepsy surgery as previously reported. Although our results need confirmation in a larger study, the observations suggest that the increased risk of SUDEP in patients failing epilepsy surgery may be due to a common factor predisposing to surgical failure, impaired HRV as well as to an increased risk of SUDEP.