Laparoscopic Electromyography and Electrostimulation of the Gastrointestinal Tract Before Placement of Theranostic Devices.

NEED: Electrical stimulation (ES) is a promising therapy for multisegmental gastrointestinal (GI) motility disorders such as gastroparesis with slow-transit constipation or chronic intestinal pseudo-obstruction. Wireless communicating GI devices for smart sensing and ES-based motility modulation will soon be available. Before placement, a potential benefit for each GI segment must be intraoperatively assessed. TECHNICAL SOLUTION: A minimally invasive multisegmental electromyography (EMG) analysis with ES of the GI tract is required. PROOF OF CONCEPT: Two porcine experiments were performed with a laparoscopic setup. Multiple hook-needle electrodes were subserosally applied in the stomach, duodenum, jejunum, ileum, and colon. EMG signals were acquired for computer-assisted motility analysis. Gastric ES, duodenal ES, jejunal ES, ileal ES, and colonic ES were applied. NEXT STEPS: Further technological and rapid regulatory solutions are desired to initialize a clinical trial of the next generation devices in the near future. CONCLUSION: We demonstrate a laparoscopic strategy with EMG analysis and ES of multiple GI segments. Thus, GI function may be evaluated before theranostic devices are placed. Extended GI resection or organ transplantation may be delayed or even avoided in affected patients.

A thin-film multichannel electrode for muscle recording and stimulation in neuroprosthetics applications.

OBJECTIVE: We propose, design and test a novel thin-film multichannel electrode that can be used for both recording from and stimulating a muscle in acute implants. APPROACH: The system is built on a substrate of polyimide and contains 12 recording and three stimulation sites made of platinum. The structure is 420 µm wide, 20 µm thick and embeds the recording and stimulation contacts on the two sides of the polyimide over an approximate length of 2 cm. We show representative applications in healthy individuals as well as tremor patients. The designed system was tested by a psychometric characterization of the stimulation contacts in six tremor patients and three healthy individuals determining the perception threshold and current limit as well as the success rate in discriminating elicited sensations (electrotactile feedback). Also, we investigated the possibility of using the intramuscular electrode for reducing tremor in one patient by electrical stimulation delivered with timing based on the electromyographic activity recorded with the same electrode. MAIN RESULTS: In the tremor patients, the current corresponding to the perception threshold and the current limit were 0.7 ± 0.2 and 1.4 ± 0.7 mA for the wrist flexor muscles and 0.4 ± 0.2 and 1.5 ± 0.7 mA for the extensors. In one patient, closed-loop stimulation resulted in a decrease of the tremor power >50%. In healthy individuals the perception threshold and current limits were 0.9 ± 0.6 and 2.1 ± 0.6 mA for the extensor carpi radialis muscle. The subjects could distinguish four or six stimulation patterns (two or three stimulation sites × two stimulation current amplitudes) with true positive rate >80% (two subjects) and >60% (one subject), respectively. SIGNIFICANCE: The proposed electrode provides a compact multichannel interface for recording electromyogram and delivering electrical stimulation in applications such as neuroprostheses for tremor suppression and closed-loop myoelectric prostheses.

Short-pulsed laser for the treatment of tattoos, pigmented lesions, scars and rejuvenation.

This review describes the use of picosecond lasers for the treatment of tattoos, pigmented lesions, scars, and their use in rejuvenation. These devices have delivered enhanced efficacy for the treatment of tattoos and pigmented lesions when compared to the older 40-50 nanosecond devices. The fractional delivery with the picosecond devices have opened up a new method of rejuvenation for photodamaged skin and the treatment of scars. The delivery of these high-energy short pulses have created zones of injury in the skin referred to as areas of laser-induced optical breakdown. These areas of damage appear to produce cytokines and chemokines which result in epidermal and dermal repair and remodeling. The dual use of these devices with the flat and the fractional optics have made these devices useful in many ways that have been unanticipated.

Extracorporeal photochemotherapy as systemic monotherapy of severe, refractory atopic dermatitis: results from a prospective trial.

BACKGROUND: Previous work has indicated that extracorporeal photochemotherapy (ECP) may be a safe and effective treatment in patients with severe atopic dermatitis. METHODS: We performed a prospective study to investigate the effect of a defined 20-week ECP protocol in patients with severe, refractory atopic dermatitis. The patient inclusion criteria included (i) disease duration of at least 1 year, (ii) SCORAD > 45, and (iii) resistance to first-line therapy, including topical steroids, topical calcineurin inhibitors, and one form of phototherapy (UVA, UVB, or PUVA) or one second-line therapy, including systemic steroids or cyclosporine. Ten patients (4 women and 6 men; age range 29 to 61 years) were enrolled and treated with two sessions of standard ECP in 2-week intervals for 12 weeks and 4-week intervals thereafter until week 20. The patients' clinical status and response was determined by SCORAD at baseline and every 2 weeks, and quality of life was assessed every 4 weeks using SKINDEX, SF-36, and FACT scores. RESULTS: There was a statistically significant (p = 0.015) reduction of the mean SCORAD by 10.3 (95% CI, 2.5 to 18.0) from 64.8 at baseline to 54.5 (i.e., 15.9% reduction) at week 20. In a subset of patients (all of female sex), the relative reduction in SCORAD after ECP was more than 25% at week 20. Improvement in quality of life measured by SKINDEX, SF-36, and FACT did not reach statistical significance. CONCLUSIONS: We detected a small but significant therapeutic effect of ECP in patients with severe, refractory atopic dermatitis.

Altered error processing following vascular thalamic damage: evidence from an antisaccade task.

Event-related potentials (ERP) research has identified a negative deflection within about 100 to 150 ms after an erroneous response--the error-related negativity (ERN)--as a correlate of awareness-independent error processing. The short latency suggests an internal error monitoring system acting rapidly based on central information such as an efference copy signal. Studies on monkeys and humans have identified the thalamus as an important relay station for efference copy signals of ongoing saccades. The present study investigated error processing on an antisaccade task with ERPs in six patients with focal vascular damage to the thalamus and 28 control subjects. ERN amplitudes were significantly reduced in the patients, with the strongest ERN attenuation being observed in two patients with right mediodorsal and ventrolateral and bilateral ventrolateral damage, respectively. Although the number of errors was significantly higher in the thalamic lesion patients, the degree of ERN attenuation did not correlate with the error rate in the patients. The present data underline the role of the thalamus for the online monitoring of saccadic eye movements, albeit not providing unequivocal evidence in favour of an exclusive role of a particular thalamic site being involved in performance monitoring. By relaying saccade-related efference copy signals, the thalamus appears to enable fast error processing. Furthermore early error processing based on internal information may contribute to error awareness which was reduced in the patients.

3D hybrid electrode structure as implantable interface for a vestibular neural prosthesis in humans.

Implantable interfaces are essential components of vestibular neural prostheses. They interface the biological system with electrical stimulation that is used to restore transfer of vestibular information. Regarding the anatomical situation special 3D structures are required. In this paper, the design and the manufacturing process of a novel 3D hybrid microelectrode structure as interface to the human vestibular system are described. Photolithography techniques, assembling technology and rapid prototyping are used for manufacturing.

Ethical issues in the development of a vestibular prosthesis.

During the development of a neural prosthesis, various ethical aspects have to be considered. These range from the basic design of the prosthesis and manufacturing of the various components and the system using biocompatible materials to extensive in vitro and in vivo testing and investigations in the animal model, before taking the final step and going to human trials. As medical systems, neural prostheses have to be proven absolutely safe before considering any clinical study. In this work, the various steps accompanying the development are described taking the example of a vestibular prosthesis currently developed within the European project CLONS.

Extracorporeal photopheresis as a treatment for patients with severe, refractory atopic dermatitis.

INTRODUCTION: Atopic dermatitis (AD) is a complex disease with a variety of possible treatment regimens. The study objective was to demonstrate that methoxsalen used in conjunction with the Uvar XTS photopheresis system (Therakos, Exton, Pa., USA) is safe and can have a clinical effect on the skin manifestations and the quality of life in patients with severe, refractory AD. METHODS: Single-arm, open-label treatment using the Uvar XTS photopheresis system. Seven patients (4 male and 3 female, median age: 47 years) with severe (SCORAD >45) AD of at least 12 months duration who in the preceding 12 months had been refractory to all 3 of the first-line therapies for AD, i.e. topical steroids, topical calcineurin inhibitors and one form of phototherapy (UVA, UVB or PUVA), or to one of the second-line therapies like systemic steroids or cyclosporine were included in the study. Treatment consisted of two extracorporeal photopheresis treatments (ExP) on successive days every 2 weeks for a minimum of 12 weeks to a maximum of 20 weeks. Quality of life assessment was performed with the SF-36 Health Survey and the Functional Assessment of Chronic Illness Therapy FACT-G Survey. Clinical improvement was documented with SCORAD assessment. RESULTS: ExP led to a significant decrease in the SCORAD score from 77.7 after 10 cycles to 55.6. Patients reported that they had begun to notice improvement of their skin conditions after 5 cycles of photopheresis. The FACT-G score showed significant improvement from 64.8 to 72.9 (p < 0.05) and the SF-36 Health Survey showed significant improvement in the emotional well-being subscores (p < 0.05). CONCLUSIONS: ExP can have a significant therapeutic effect on the skin and quality of life improvement in a selected group of patients with severe AD who are refractory to conventional forms of therapy. However, larger studies are needed to further evaluate its therapeutic potential.

A pilot study to optimize laser-assisted hair removal using real-time high-speed infrared imaging.

OBJECTIVE: The aim of this study was to investigate thermal effects on the skin surface during laser-assisted hair removal using real-time high-speed infrared imaging. BACKGROUND DATA: Although hair laser removal (HLR) can be considered an inherently safe treatment, there may be approaches to optimise the benefit/risk ratio of this common therapeutic and cosmetic procedure. METHODS: In this pilot study on three subjects, a ruby laser equipped with a cryogen spray cooling (CSC) system was used to investigate the effect of different CSC durations and delay times between CSC and the laser impulse. Skin surface temperature (SST) was assessed in real-time using a high-speed infrared camera (ThermaCam Phoenix) and a special image analysis software (analySIS Doku). RESULTS: There was no substantial difference of SST between the use of CSC spurts of 10 and 20 msec (6.1 degrees C versus 5.7 degrees C). The use of single laser and cooling parameters revealed baseline SST of 31.7 degrees C, immediately after CSC (10 ms) SST of 6.5 degrees C, and after laser pulse SST of 47 degrees C. Using fluences of 10-20 J/cm(2), a marked difference in temperature was observed between the skin surface and hair (e.g., 26.7 degrees C versus 57.5 degrees C). SST of 62-64 degrees C was observed using fluences of 18-20 J/cm(2), resulting in adverse effects. A maximum SST of 59 degrees C was observed using a CSC spurt of 40 msec, whereas a maximum SST of 60 degrees C was recorded for 30, 20, and 10 msec. The use of CSC delay time of 600 msec revealed baseline SST of 34.6 degrees C, immediately after CSC (10 msec) SST of 5.2 degrees C, after 600 msec delay SST of 21.5 degrees C, and SST of 60 degrees C following the laser pulse. By contrast, 100 msec delay time revealed baseline SST of 34.8 degrees C, immediately after CSC (10 ms) SST of 7 degrees C, after 100 msec delay SST of 7.5 degrees C, and SST of 55.2 degrees C following the laser pulse. CONCLUSION: Our preliminary data indicate that side effects of HLR can be avoided using CSC duration of 10 msec with a delay of about 200 msec. Short delay times between the CSC and laser pulse seem to result in lower post-irradiation SST and may therefore lead to less adverse effects. With regard to the fluence used in HLR, it is of importance that the maximum SST remains below 60 degrees C. Based on these preliminary results, real-time high-speed infrared imaging seems to be an interesting method to study the thermodynamics on skin surface during laser treatment.

Multisensory space representations in the macaque ventral intraparietal area.

Animals can use different sensory signals to localize objects in the environment. Depending on the situation, the brain either integrates information from multiple sensory sources or it chooses the modality conveying the most reliable information to direct behavior. This suggests that somehow, the brain has access to a modality-invariant representation of external space. Accordingly, neural structures encoding signals from more than one sensory modality are best suited for spatial information processing. In primates, the posterior parietal cortex (PPC) is a key structure for spatial representations. One substructure within human and macaque PPC is the ventral intraparietal area (VIP), known to represent visual, vestibular, and tactile signals. In the present study, we show for the first time that macaque area VIP neurons also respond to auditory stimulation. Interestingly, the strength of the responses to the acoustic stimuli greatly depended on the spatial location of the stimuli [i.e., most of the auditory responsive neurons had surprisingly small spatially restricted auditory receptive fields (RFs)]. Given this finding, we compared the auditory RF locations with the respective visual RF locations of individual area VIP neurons. In the vast majority of neurons, the auditory and visual RFs largely overlapped. Additionally, neurons with well aligned visual and auditory receptive fields tended to encode multisensory space in a common reference frame. This suggests that area VIP constitutes a part of a neuronal circuit involved in the computation of a modality-invariant representation of external space.

Morbihan's disease: treatment with CO2 laser blepharoplasty.

Morbihan's disease is a rare condition characterized by chronic persistent erythema and edema of the upper half of the face. Therapeutic regimens such as X-ray irradiation, lymphatic massage, interferon gamma injections, antihistamines, and high-dose antibiotics are often unsatisfactory. Promising results in some patients have been achieved by a systemic combination therapy of isotretinoin with ketotifen or clofazimine. Excision of redundant edematous tissue may be an alternative. We present a 67-year-old Caucasian patient with a two-year history of right lower and upper eyelid swelling and erythema. Systemic therapies with corticocosteroids and antibiotics were not successful, but CO2 laser blepharoplasty led to good cosmetic results with marked improvement of visual impairment and no recurrence during the six-month follow-up period.

Low-dose UVA1 phototherapy in systemic sclerosis: effects on acrosclerosis.

BACKGROUND: Increased collagen synthesis, vascular damage, and T-lymphocytic infiltration contribute to the development of systemic sclerosis. Preliminary studies revealed the effectiveness of low-dose UVA1 phototherapy in acrosclerosis. OBJECTIVE: We sought to confirm data of a pilot study revealing the efficacy of low-dose UVA1 irradiation in acrosclerosis in a larger number of patients. METHODS: Symptoms of 18 patients receiving low-dose UVA1 phototherapy were evaluated clinically and biometrically in an open, nonrandomized study. A number of pretherapeutic and posttherapeutic biopsy specimens were tested immunohistochemically for matrix-metalloproteinase-1. RESULTS: UVA1 irradiation led to softening of former stiffness reflected by a significant decrease of the hand score, increase of total skin distension, and reduction of skin thickness. Posttherapeutically, matrix-metalloproteinase-1 immunolabeling revealed a significant dermal elevation of collagenase. CONCLUSION: Low-dose UVA1 phototherapy is a capable treatment option for acrosclerosis. Its beneficial effect may be mediated by the induction of collagenases and a reduction of collagen deposition and cellular infiltration.

Representation of sound source direction in the superior colliculus of the guinea pig in a virtual auditory environment.

The deep layers of the superior colliculus (SC) receive visual, auditory, and somatosensory input. A major function of the SC is the control of orientation movements of the eye, head, and pinna. While a topographical map for sound source direction remains elusive in primary auditory structures of mammals, such a map for azimuthal sound source directions has been reported in the deep layers of the SC. Moreover, a gradient of elevation tuning has been also seen in the SC of ferrets and cats. Here we demonstrate that a virtual auditory environment can be used to reveal azimuthal and elevational topography for auditory spatial receptive fields in neurons in the SC of guinea pigs. Individual, head-related transfer functions (HRTF) were measured in ten guinea pigs for 122 directions in the upper hemispheric field and convolved with white noise. Many neurons (39%) in the deep layers showed robust responses to these virtual sounds, and the majority of these neurons had small spatial receptive fields that were restricted to the contralateral hemifield. Best directions varied from 0 degree to 135 degree azimuth along the contralateral side and from --10 degree to 60 degree elevation. Like previous studies using free-field stimulation, a gradient of best azimuth direction was found along the rostral-caudal axis, with rear directions represented caudally and front directions rostrally. The topographical organization for best elevations had not been studied previously in the guinea pig. We found that it roughly followed the mediolateral axis, with preference for high elevations represented medially and low elevations laterally. A similar organization using free-field stimulation has been reported in the ferret.

Low-dose ultraviolet A1 phototherapy for extragenital lichen sclerosus: results of a preliminary study.

BACKGROUND: Lichen sclerosus (LS) is a chronic inflammatory skin disease in which numerous therapies have been used, with only limited success. Because low-dose UVA1 phototherapy has been shown to be an effective treatment option for localized scleroderma, which shares several similar clinical and histologic features with LS, we initiated a clinical trial with this phototherapeutic modality in patients with LS. METHODS: Ten patients suffering from extragenital LS were treated with low-dose UVA1 phototherapy 4 times weekly with single UVA1 doses of 20 J/cm(2). Forty treatment sessions were performed within 10 weeks, resulting in a cumulative UVA1 dose of 800 J/cm(2). RESULTS: Low-dose UVA1 phototherapy resulted in a marked reduction of the clinical score and a significant (P <.05) decrease of ultrasonographically measured skin thickness as well as a highly significant (P <.001) increase of dermal density. The patients reported a remarkable softening and repigmentation of the affected skin. CONCLUSION: Analogous to the treatment results in localized scleroderma, low-dose UVA1 phototherapy seems to be an effective and well-tolerated treatment option for extragenital LS.