Clinical evaluation of a new fractional ablative 2910 nm erbium laser on photodamaged skin: A pilot study.

OBJECTIVE: To examine the efficacy and safety of a new fractional, ablative erbium:glass fiber (Er:glass) laser (2910 nm) at improving clinical signs of photodamaged skin. MATERIALS AND METHODS: Thirty-seven healthy participants aged 38-75 years with photodamaged skin were enrolled into two treatment groups. Group A (n = 14) received up to four laser treatments with mild settings, and focal facial subunits were treated with deeper settings. Group B (n = 23) received a single treatment using deeper settings. Following treatment, pain scores and severity and duration of skin responses (erythema, edema, and pinpoint bleeding) were assessed. Primary outcome was the improvement in participant and investigator Global Aesthetic Improvement Scale (GAIS) at 3-month follow-up. Secondary outcomes were participant satisfaction with treatment and whether they would repeat treatment. RESULTS: Thirty-five participants completed the study (n = 1 lost to follow up in each group). Both groups had similar mean participant and investigator GAIS scores of 3/5 corresponding to "Improvement." All but two patients (both from Group A) reported improvement, satisfaction with treatment, and would repeat treatment. Posttreatment skin responses were mild-to-moderate, lasting up to 5 days. There was no scarring or dyspigmentation. CONCLUSION: The 2910 nm Er:glass laser provided improvement in photoaging with high patient satisfaction.

Eccentric Versus Concentric Exercises in Patients With Rheumatoid Arthritis and Rotator Cuff Tendinopathy: A Randomized Comparative Study.

OBJECTIVE: To determine the efficacy of concentric vs. eccentric exercise in improving shoulder function, pain, and tendon characteristics for patients with rheumatoid arthritis and rotator cuff tendinopathy. METHODS: Forty patients with rheumatoid arthritis and rotator cuff tendinopathy were divided into either concentric or eccentric exercise groups, with 20 patients in each group. Patients received 12 sessions at a pace of 3 sessions per week. Shoulder Pain and Disability Index (SPADI), the visual analogue scale (VAS), supraspinatus and subscapularis thickness, echo pixels, and the Disease Activity Score-28-erythrocyte sedimentation rate (DAS-28-ESR) were assessed at baseline and post-treatment. RESULTS: There was a significant difference between the concentric and eccentric groups regarding SPADI and VAS scores in favor of the eccentric group. However, there was no significant difference between the two groups regarding tendon thickness, echo pixels, or DAS-28-ESR. CONCLUSION: Eccentric exercises were more effective than concentric exercises in improving shoulder function and pain intensity. However, neither of the two types of exercises was superior in improving tendon characteristics or disease activity.

Sparsity-based method for ring artifact elimination in computed tomography.

Ring artifact elimination is one of the popular problems in computed tomography (CT). It appears in the reconstructed image in the form of bright or dark patterns of concentric circles. In this paper, based on the compressed sensing theory, we propose a method for eliminating the ring artifact during the image reconstruction. The proposed method is based on representing the projection data by a sum of two components. The first component contains ideal correct values, while the latter contains imperfect error values causing the ring artifact. We propose to minimize some sparsity-induced norms corresponding to the imperfect error components to effectively eliminate the ring artifact. In particular, we investigate the effect of using different sparse models, i.e. different sparsity-induced norms, on the accuracy of the ring artifact correction. The proposed cost function is optimized using an iterative algorithm derived from the alternative direction method of multipliers. Moreover, we propose improved versions of the proposed algorithms by incorporating a smoothing penalty function into the cost function. We also introduce angular constrained forms of the proposed algorithms by considering a special case as follows. The imperfect error values are constant over all the projection angles, as in the case where the source of ring artifact is the non-uniform sensitivity of the detector. Real data and simulation studies were performed to evaluate the proposed algorithms. Results demonstrate that the proposed algorithms with incorporating smoothing penalty and their angular constrained forms are effective in ring artifact elimination.

Safety and Efficacy of Nanosecond Pulsed Electric Field Treatment of Seborrheic Keratoses.

BACKGROUND: Nanosecond pulsed electric field technology (also known as Nano-Pulse Stimulation or NPS) is a nonthermal, drug-free, energy-based technology that has demonstrated effects on cellular structures of the dermis and epidermis in previous clinical studies. OBJECTIVE: To evaluate the safety and efficacy of a single NPS treatment for clearing seborrheic keratoses (SKs). MATERIALS AND METHODS: This study was a prospective, randomized, open-label, multisite, nonsignificant risk trial in which each subject served as their own control. Fifty-eight subjects had 3 of 4 confirmed SK lesions treated, resulting in 174 total treated lesions. Subjects returned for 5 to 6 follow-up evaluations and photographs. RESULTS: At 106 days after NPS treatment, 82% of treated seborrheic keratoses were rated clear or mostly clear by the assessing physician. Seventy-one percent of lesions were rated clear or mostly clear by the 3 independent reviewers based on the 106-day photographs. All treated subjects returned for all study visits, and 78% of the subjects were satisfied or mostly satisfied with the outcome of the treatment. No adverse events were reported. CONCLUSION: The NPS procedure was well tolerated and effective in the removal of SKs.

Safety and Efficacy of Nanosecond Pulsed Electric Field Treatment of Sebaceous Gland Hyperplasia.

BACKGROUND: Nanosecond pulsed electric field (nsPEF) technology involves delivery of ultrashort pulses of electrical energy and is a nonthermal, drug-free technology that has demonstrated favorable effects on cellular structures of the dermis and epidermis. OBJECTIVE: Determine the tolerability and effectiveness of nsPEF treatment of sebaceous gland hyperplasia (SGH). METHODS: This study was a prospective, randomized, open-label, multisite, nonsignificant risk trial in which each subject served as their own control. After injection of local anesthetic, high-intensity, ultrashort pulses of electrical energy were used to treat 72 subjects resulting in a total of 222 treated lesions. Subjects returned for 3 to 4 follow-up evaluations with photographs. RESULTS: At the final study visit, 99.6% of treated SGH lesions were rated clear or mostly clear and 79.3% of the subjects were satisfied or mostly satisfied with the outcome. At 60 days after nsPEF treatment, 55% of the lesions were judged to have no hyperpigmentation and 31% exhibited mild post-treatment hyperpigmentation. At the last observation for all lesions, 32% of the 222 lesions were noted as having slight volume loss. CONCLUSION: Nanosecond pulsed electric field procedure is well tolerated and is very effective in the removal of SGHs. TRIAL REGISTRATION: ClinicalTrials.gov NCT03612570.

Fast-adapting mechanoreceptors are important for force control in precision grip but not for sensorimotor memory.

Sensory feedback from cutaneous mechanoreceptors in the fingertips is important in effective object manipulation, allowing appropriate scaling of grip and load forces during precision grip. However, the role of mechanoreceptor subtypes in these tasks remains incompletely understood. To address this issue, psychophysical tasks that may specifically assess function of type I fast-adapting (FAI) and slowly adapting (SAI) mechanoreceptors were used with object manipulation experiments to examine the regulation of grip force control in an experimental model of graded reduction in tactile sensitivity (healthy volunteers wearing 2 layers of latex gloves). With gloves, tactile sensitivity decreased significantly from 1.9 ± 0.4 to 12.3 ± 2.2 µm in the Bumps task assessing function of FAI afferents but not in a grating orientation task assessing SAI afferents (1.6 ± 0.1 to 1.8 ± 0.2 mm). Six axis force/torque sensors measured peak grip (PGF) and load (PLF) forces generated by the fingertips during a grip-lift task. With gloves there was a significant increase of PGF (14 ± 6%), PLF (17 ± 5%), and grip and load force rates (26 ± 8%, 20 ± 8%). A variable-weight series task was used to examine sensorimotor memory. There was a 20% increase in PGF when the lift of a light object was preceded by a heavy relative to a light object. This relationship was not significantly altered when lifting with gloves, suggesting that the addition of gloves did not change sensorimotor memory effects. We conclude that FAI fibers may be important for the online force scaling but not for the buildup of a sensorimotor memory.

Peripheral Innervation in Children With Global Developmental Delay: Biomarker for Risk for Self-Injurious Behavior?

The relation between somatosensory mechanisms and self-injury among children with neurologic impairments associated with developmental delay is not well understood. We evaluated the feasibility of procuring skin biopsies to examine epidermal nerve fiber density and reported self-injury. Following informed parental consent, epidermal skin biopsies were obtained from a distal leg site with no pre-existing skin damage from 11 children with global developmental delay (55% male; mean age = 36.8 months, 17-63 months). Visual microscopic examination and quantitative analyses showed extremely high epidermal nerve fiber density values for some children. Children with reported self-injury (5/11) had significantly (P < .02) greater density values (138.8, standard deviation = 45.5) than children without self-injury (80.5, standard deviation = 17.5). Results from this novel immunohistologic analysis of skin in very young children with neurodevelopmental delays suggest it may be a useful tool to study peripheral innervation as a possible sensory risk factor for self-injury.

Postganglionic sudomotor denervation in patients with multiple system atrophy.

OBJECTIVE: To evaluate postganglionic autonomic involvement in multiple system atrophy (MSA). METHODS: We quantified sudomotor innervation in skin biopsy of 29 patients with MSA (19 male and 10 female; age 60.0 ± 7.7 years) and 29 age- and sex-matched healthy subjects. Samples were obtained from thigh and leg and, in 20 out of the 29 cases, also from fingertip. Dysautonomic complaints were evaluated by SCOPA-AUT, a self-administered questionnaire. Sudomotor function was evaluated in a subgroup of patients by the silastic imprint test. Skin samples were processed by indirect immunofluorescence using pan-neuronal and selective cholinergic markers. Total length of sudomotor nerves was measured on digital confocal images using a semiautomated morphometric approach. RESULTS: Measurements of sudomotor nerve density (total length of nerve per volume of glandular tissue) favorably correlated to values obtained using a stereologic unbiased method. Sudomotor nerve density was lower in patients compared to controls in all the examined sites (0.9 ± 0.2 vs 1.9 ± 0.4 nm/µm(3), p < 0.001, in fingertip; 0.7 ± 0.2 vs 1.9 ± 0.5 nm/µm(3), p < 0.001, in thigh; 0.6 ± 0.2 vs 1.8 ± 0.4 nm/µm(3), p < 0.001, in leg). CONCLUSIONS: Our data support the hypothesis that postganglionic impairment occurs in MSA and may contribute with the coexisting degeneration of central structures to the development of dysautonomic disorders in this condition.

Enlarged vestibular aqueduct in congenital non-syndromic sensorineural hearing loss in egypt.

To estimate the frequency of isolated enlarged vestibular aqueduct (EVA) in patients with non-syndromic sensorineural hearing loss (SNHL) in an Egyptian population sample and to correlate its size with the degree of hearing loss. The study group comprised 16 patients (32 ears) suffering from non-syndromic SNHL since childhood. After a complete basic audiological evaluation, all patients were submitted to non contrast CT scan of the petrous bone in both axial & coronal planes. Vestibular aqueduct (VA) was measured at two points (midpoint & operculum) on right & left sides. The study group was divided according to VA size into three groups: group A, B and C. Group A included 6 ears (4 patients) with EVA, group B included 11 ears (7 patients) with borderline EVA and group C included 15 ears (9 patients) with normal VA size. There were no statistically significant differences between the three groups as regards laterality, degree of hearing loss and audiometric configuration. There was no correlation between VA midpoint & operculum and different variables (age and average pure tone thresholds). However, a significant correlation between VA midpoint & operculum was found. EVA was diagnosed in 6 out of 32 ears (18.75%) in the study sample. EVA size was not related to the degree of hearing loss or configuration. Despite the insignificant findings, moderate and high frequency sloping SNHL were considered the most common findings seen in patients with EVA.

Variation in quantitative sensory testing and epidermal nerve fiber density in repeated measurements.

Quantitative sensory testing (QST) is commonly used to evaluate peripheral sensory function in neuropathic conditions. QST measures vary in repeated measurements of normal subjects but it is not known whether QST can reflect small changes in epidermal nerve fiber density (ENFd). This study evaluated QST measures (touch, mechanical pain, heat pain and innocuous cold sensations) for differences between genders and over time using ENFd as an objective-independent measure. QST was performed on the thighs of 36 healthy volunteers on four occasions between December and May. ENFd in skin biopsies was determined on three of those visits. Compared to men, women had a higher ENFd, a difference of 12.2 ENFs/mm. They also had lower tactile and innocuous cold thresholds, and detected mechanical pain (pinprick) at a higher frequency. Heat pain thresholds did not differ between genders. By the end of the 24-week study, men and women showed a small reduction (p<0.05) in the frequency of sharp mechanical pain evoked by pinprick whereas tactile and thermal thresholds showed no change. This coincided with a small decrease in ENFd, 4.18 ENFs/mm. Variation in measurements over time was large in a fraction of normal subjects. We conclude that most QST measures detect relatively large differences in epidermal innervation (12.2 ENFs/mm), but response to mechanical pain was the only sensory modality tested with the sensitivity to detect small changes in innervation (4.18 ENFs/mm). Since some individuals had large unsystematic variations, unexpected test results should therefore alert clinicians to test additional locations.

A randomized, controlled, open-label study of the long-term effects of NGX-4010, a high-concentration capsaicin patch, on epidermal nerve fiber density and sensory function in healthy volunteers.

UNLABELLED: Desensitization of nociceptive sensory nerve endings is the basis for the therapeutic use of capsaicin in neuropathic pain syndromes. This study evaluated the pharmacodynamic effects of a single 60-minute application of NGX-4010, a high-concentration (8% w/w) capsaicin patch, on both thighs of healthy volunteers. Epidermal nerve fiber (ENF) density and quantitative sensory testing (QST) using thermal, tactile, and sharp mechanical-pain (pinprick) stimuli were evaluated 1, 12 and 24 weeks after capsaicin exposure. After 1 week, there was about an 80% reduction of ENF density compared to unexposed sites. In addition, there was about an 8% increase in tactile thresholds compared to baseline and the proportion of stimuli reported as sharp mechanical pain decreased by about 15 percentage points. Twelve weeks after exposure to capsaicin, ENF regeneration was evident, but not complete, and sharp mechanical-pain sensation and tactile thresholds did not differ from unexposed sites. Nearly full (93%) ENF recovery was observed at 24 weeks. No statistically significant changes in heat- or cold-detection thresholds were observed at any time point. NGX-4010 was generally well tolerated. Transient, mild warming or burning sensations at the site of application were common adverse effects. PERSPECTIVE: This article evaluates the effect of a single 60-minute NGX-4010 application on ENF density and QST in healthy volunteers followed for 24 weeks. The results help predict the long-term safety of NGX-4010 applications in patients.

Sensory deficit in Parkinson's disease: evidence of a cutaneous denervation.

Sensory disturbances are part of the clinical picture of Parkinson's disease. Abnormalities in sensory processing, through a basal ganglia involvement, are thought to be responsible for the sensory dysfunction since sensory nerve conduction velocity (NCV) is usually normal. However, NCV does not examine small fibres or terminal endings of large sensory fibres, whereas skin biopsy is more suitable for these purposes. To evaluate peripheral sensory nerves in Parkinson's disease, we studied cutaneous free and encapsulated sensory nerve endings in 18 patients and 30 healthy controls using 3-mm punch biopsies from glabrous and hairy skin. Ten patients had additional skin biopsies from the contralateral side. Further evaluation included NCV and Quantitative Sensory Testing. Parkinson's disease patients showed a significant increase in tactile and thermal thresholds (P < 0.01), a significant reduction in mechanical pain perception (P < 0.01) and significant loss of epidermal nerve fibres (ENFs) and Meissner corpuscles (MCs) (P < 0.01). In patients with bilateral biopsies, loss of pain perception and ENFs was higher on the more affected side (P < 0.01). We found evidence suggesting attempts at counteracting degenerative processes as increased branching, sprouting of nerves and enlargement of the vascular bed. Morphological and functional findings did not correlate with age or disease duration. Disease severity correlated with loss of MCs and reduction in cold perception and pain perception. We demonstrated a peripheral deafferentation in Parkinson's disease that could play a major role in the pathogenesis of the sensory dysfunction.

Stimulated growth of human and pig epidermal nerve fibers by tape stripping.

Nerve growth studies in adults usually rely upon nerve regeneration that follows axon disruption. In this study elongation of the epidermal nerve fibers occurred in human and pig epidermis stimulated to hypertrophy by removing the stratum corneum with repetitive applications of tape (tape stripping). Epidermal thickening was accompanied by elongation of the epidermal nerve fibers. This study demonstrates that changing the cellular and chemical environment of nerves by tape stripping is a feasible method to study nerve fiber growth in a physiological manner.

Light patch: preliminary report of a novel form of blue light delivery for the treatment of actinic keratosis.

OBJECTIVE: To evaluate a novel light patch formulated for blue light delivery and topical activation of gamma-aminolevulinic acid (ALA) during photodynamic therapy for the treatment of actinic keratosis (AK). MATERIALS AND METHODS: Ten volunteers with past unsuccessful treatment of AK were enrolled. Areas with AK lesions were treated with 20% ALA (Levulan) for an incubation period of 1 hour. Half of the area was treated with blue light patches (the patch emits 431 to 515 nm wavelength, 55.6 mJ/cm2 over 20 minutes), and the other half was left uncovered (control). The percentage of visible AK lesions cleared at the 3-month follow-up determined therapeutic efficacy. RESULTS: The mean lesion count for all treatment areas was decreased from 7.60 to 2.40 (p<.01). The subjects had slight burning or itching and mild to moderate erythema. One subject developed a blister at the treatment site. Controls had clearance of 30%, 17%, and 20% for the face, scalp, and hands, respectively. Patients were satisfied with the results and noticed an improvement in skin texture. CONCLUSION: Preliminary results show that the blue light patch is a potentially safe, effective, and alternative method for light delivery and topical ALA activation during photodynamic therapy of AK.

Confocal microscopy study of nerves and blood vessels in untreated and treated port wine stains: preliminary observations.

BACKGROUND AND OBJECTIVE: Vascular ectasia in port wine stain birthmarks (PWS) might result from reduced innervation with loss of autonomic stimulation. We investigated this theory and evaluated nerve and blood vessel density, and mean blood vessel size in untreated and treated PWS skin. METHODS: Skin biopsy specimens were obtained from uninvolved skin, untreated PWS, PWS with a good response to laser treatment and PWS with a poor response to laser treatment. Confocal microscopy was performed to determine nerve and blood vessel density, and mean blood vessel size. RESULTS: Nerve density was significantly decreased in all PWS sites compared to uninvolved skin. Mean blood vessel diameter was larger in untreated compared to treated PWS. PWS with a good response to treatment had decreased nerve density but blood vessel density and mean diameter was relatively normal. PWS with a poor response to treatment had decreased nerve density but increased blood vessel density and mean blood vessel diameter compared to normal skin. CONCLUSION: Nerve density was decreased in all evaluated PWS sites and this may be a factor in lesion pathogenesis. PWS blood vessel size correlated with pulsed dye laser response and may prove to be a useful prognostic indicator of therapeutic outcome.