Minimally ablative resurfacing with the confluent 2,790 nm erbium:YSGG laser: a pilot study on safety and efficacy.

BACKGROUND: The 2,790 nm Er:YSGG wavelength has a lower water absorption coefficient than the 2,940 nm Er:YAG, but a higher coefficient than the 10,600 nm CO(2) laser. This allows ablative resurfacing with mild thermal coagulation, which may increase clinical efficacy while reducing patient downtime. OBJECTIVES: To evaluate the efficacy and safety of the confluent 2,790 nm Erbium:YSGG (Pearl™, Cutera) laser for facial rejuvenation. STUDY DESIGN/MATERIALS AND METHODS: Eleven subjects (mean age 50, skin types I-III) with mild to moderate photodamage and wrinkles had two facial treatments with the 2,790 nm Er:YSGG laser using a fluence of 3.5 J/cm(2), pulse duration of 0.4 msecond, and 20% overlap. Treatments were performed 6 weeks apart. Pre-auricular biopsies from five subjects were evaluated at baseline and 6 weeks after the final treatment. Data from blinded photo assessments and subjects' self-assessment of improvement were analyzed 6 weeks after the final treatment. Additionally, long-term safety and efficacy were evaluated 2 years after the final treatment. RESULTS: Histologically, 80% of subjects had new collagen formation in the dermal grenz zone, and 60% had increased epidermal thickness. Almost all subjects (91%) showed improvement in tone/texture, 82% of subjects showed improvement in dyschromia and fine lines, and 54% showed improvement in wrinkles 6 weeks after the final treatment. Subjects' self assessment indicated "significant" to "dramatic" improvement in dyschromia (91% of subjects) and tone/texture (82%) 6 weeks after the final treatment. All subjects saw "mild" to "significant" improvement in fine lines and wrinkles. At the 2-year follow-up visit, 57% of the overall improvement achieved at 6 weeks was maintained. No adverse events were reported throughout the study. CONCLUSION: Ablative resurfacing with the 2,790 nm Er:YSGG laser demonstrated visible improvement in photodamage with good tolerability and minimal downtime. Subjects were highly satisfied, especially with respect to dyschromia, skin tone, and texture.

Survey of regional laser centers: a Minnesota perspective.

BACKGROUND: Laser use in medicine is rapidly expanding as patients seek treatment for medical and cosmetic purposes. Concern is mounting about the unsupervised use of lasers and similar devices by nonphysician personnel. Minnesota is currently one of the few states with no legislation regarding the uses of lasers. OBJECTIVE: To determine whether laser centers in Minnesota meet professional standards and guidelines for patient safety. METHODS AND MATERIALS: Public resources were used to identify all businesses with laser services in Minnesota cities with a population of at least 1,000 people. Each laser center was contacted, and a "secret shopper," a person who posed as a potential patient administered a telephone survey. RESULTS: A wide range of physicians and nonphysician personnel offer laser services in Minnesota. Supervision was not standardized and varied widely across the laser centers. CONCLUSIONS: As the demand for laser services increases, the use of lasers must be clearly defined and regulated to prevent patient injury. The authors have indicated no significant interest with commercial supporters.

Histologic analysis of a 2,940 nm fractional device.

BACKGROUND AND OBJECTIVES: An evaluation of the histological effects of a 2,940 nm fractional erbium:YAG (Er:YAG) laser device with adjustable depth and coagulation settings in a human abdominoplasty model. The goal of this study was to use light and confocal microscopy to determine the dimensions of the microthermal zones (MTZs) created by this device in the epidermal and dermal layers. STUDY DESIGN/MATERIALS AND METHODS: Three subjects were consented and treated after being randomly assigned to a laser depth of either 250 µm, 500 µm, or 1,000 µm. Four coagulation levels were tested in each subject. Two biopsies were taken immediately, 1 and 2 weeks post-treatment from each zone and viewed by light and confocal microscopy. Two blinded observers examined the sections for changes in collagen and measured depth and width of the MTZs. Coagulation was assessed and recorded as the depth and width of denaturation; measured as the depth and width of ablation plus surrounding thickness of thermal necrosis from dissipated heat. RESULTS: Light microscopy findings in all treated samples showed a perforated epidermis and dermis immediately after treatment. The depths of ablation produced did not accurately reflect the three different laser settings. Depths of denaturation also did not increase with increased coagulation level settings as expected. The width of ablation in the MTZs, a non-adjustable setting, was the most accurate and reproducible in all subjects. Confocal microscopy samples revealed the presence of collagen remodeling in the dermis, which increased significantly at 1 and 2 weeks post-treatment. CONCLUSIONS: Treatment with the 2,940 nm Er:YAG device led to significant changes of the dermis at light microscopy levels. The adjustable laser depth and coagulation settings did not produce predictable depths of ablation or denaturation, possibly as a result of the variation of tissue hydration properties among individuals. Increased collagen remodeling was seen in the dermis in all subjects at 1 and 2 weeks post-treatment.

Semi-Automated method of analysis of horizontal histological sections of skin for objective evaluation of fractional devices.

BACKGROUND AND OBJECTIVE: The treatment of skin with fractional devices creates columns of micro-ablation or micro-denaturation depending on the device. Since the geometric profiles of thermal damage depend on the treatment parameters or physical properties of the treated tissue, the size of these columns may vary from a few microns to a few millimeters. For objective evaluation of the damage profiles generated by fractional devices, this report describes an innovative and efficient method of processing and evaluating horizontal sections of skin using a novel software program. MATERIALS AND METHODS: Ex vivo porcine skin was treated with the Lux1540/10, Lux1540 Zoom and Lux2940 with 500 optics. Horizontal (radial) sections of biopsies were obtained and processed with H&E and NBTC staining. Digital images of the histologic sections were taken in either transmission or reflection illumination and were processed using the SAFHIR program. RESULTS: NBTC- and H&E-stained horizontal sections of ex vivo skin treated with ablative and non-ablative fractional devices were obtained. Geometric parameters, such as depth, diameter, and width of the coagulated layer (if applicable), and micro-columns of thermal damage, were evaluated using the SAFHIR software. The feasibility of objective comparison of the performance of two different fractional devices was demonstrated. CONCLUSION: The proposed methodology provides a comprehensive, objective, and efficient approach for the comparison of various fractional devices. Correlation of device settings with the objective dimensions of post-treatment damage profiles serve as a powerful tool for the prediction and modulation of clinical response.

Pilot investigation of the correlation between histological and clinical effects of infrared fractional resurfacing lasers.

METHODS: Yucatan Black pig skin was treated with a 1,540-nm erbium (Er):glass laser (Lux1540, 15 and 30 mJ) and two 1,550-nm Er-doped fiber lasers (Fraxel SR750 and SR1500, 8, 10, and 12 mJ). Histologic sections were examined to determine the depth of damage and to correlate subjects' clinical response. Concurrently, six subjects with photodamaged skin received three split-face and ipsilateral dorsal hand treatments with the 1,540-nm Er:glass laser on one side and one of the 1,550-nm Er-doped lasers (Fraxel SR750) on the other. RESULTS: The 1,550-nm Er-doped lasers, using lower fluences and higher densities, produced shallower micro-columns than the 1,540-nm Er:glass device at higher fluences and lower densities (mean depths 250-275 microm vs 425-525 microm, respectively). Blinded assessors found greater overall improvement in pigmentation with the 1,550-nm Er-doped laser and better overall improvement in texture with the 1,540-nm Er:glass laser. CONCLUSIONS: Greater densities of shallower damage columns at lower energies may better improve pigmentation, whereas deeper injuries, using higher energies and moderate densities, may better improve texture. This pilot study did not compare similar fluences and histologic damage between the two systems, and newer available systems allow for greater depth of penetration.

Ultrastructural effects of an infrared handpiece on forehead and abdominal skin.

BACKGROUND: Collagen fibril contraction has been shown to be associated with tissue tightening by nonablative skin rejuvenation. Transmission electron microscopy has proven to be an effective method for characterizing collagen contraction delivered by ablative and nonablative devices used on human skin. OBJECTIVE: The purpose of this two-part study was to evaluate ultrastructural changes in cadaveric forehead skin and live abdominal skin by transmission electron microscopy for different fluence levels using the Titan infrared handpiece (Cutera, Inc., Brisbane, CA). This device is a noncoherent selectively filtered infrared device operating in the 1,100- to 1,800-nm bandwidth, intended to provide dermal heating. METHODS AND MATERIALS: Cadaveric forehead skin at 37 degrees C was treated with a 1x1.5-cm spot at fluences of 50 and 100 J/cm2. Informed consent was obtained and abdominal skin of one patient (before abdominoplasty) was treated in vivo with a 1x1.5-cm spot at fluences of 30, 45, and 65 J/cm2. Punch biopsies of the treatment areas and a control area were obtained immediately after treatment. Transmission electron microscopy at depths of 0 to 1 and 1 to 2 mm was performed for each biopsy to evaluate morphologic alterations of collagen fibrils in treated areas compared to the control area. RESULTS: In the cadaveric forehead skin samples, the collagen fibril alteration was greatest in the depth range of 1 to 2 mm for both fluence settings. In the abdominal skin samples, collagen fibril alteration was not seen in the control site but was observed at all treatment levels at both the 0 to 1 and the 1 to 2-mm depths, with the least alteration seen at the shallow depth and the lowest fluence. CONCLUSIONS: Our findings suggest that collagen fibril denaturation, consistent with fibril thermocontraction, occurs immediately after infrared tissue tightening. Collagen denaturation occurs at a depth range appropriate for deep dermal treatments. The peak in collagen fibril alteration at 1 to 2 mm is consistent with contact cooling protecting the more superficial layers of the skin.

Ultrastructural evaluation of multiple pass low energy versus single pass high energy radio-frequency treatment.

BACKGROUND AND OBJECTIVE: The radio-frequency (RF) device is a system capable of volumetric heating of the mid to deep dermis and selective heating of the fibrous septa strands and fascia layer. Clinically, these effects promote dermal collagen production, and tightening of these deep subcutaneous structures. A new technique of using multiple low energy passes has been described which results in lower patient discomfort and fewer side effects. This technique has also been anecdotally described as giving more reproducible and reliable clinical results of tissue tightening and contouring. This study will compare ultrastructural changes in collagen between a single pass high energy versus up to five passes of a multiple pass lower energy treatment. STUDY DESIGN/MATERIALS AND METHODS: Three subjects were consented and treated in the preauricular region with the RF device using single or multiple passes (three or five) in the same 1.5 cm(2) treatment area with a slight delay between passes to allow tissue cooling. Biopsies from each treatment region and a control biopsy were taken immediately, 24 hours or 6 months post treatment for electron microscopic examination of the 0-1 mm and 1-2 mm levels. Sections of tissue 1 mm x 1 mm x 80 nm were examined with an RCA EMU-4 Transmission Electron Microscope. Twenty sections from 6 blocks from each 1 mm depth were examined by 2 blinded observers. The morphology and degree of collagen change in relation to area examined was compared to the control tissue, and estimated using a quantitative scale. RESULTS: Ultrastructural examination of tissue showed that an increased amount of collagen fibril changes with increasing passes at energies of 97 J (three passes) and 122 J (five passes), respectively. The changes seen after five multiple passes were similar to those detected after much more painful single pass high-energy treatments. CONCLUSIONS: This ultrastructural study shows changes in collagen fibril morphology with an increased effect demonstrated at greater depths of the skin with multiple low-fluence passes and at lesser depths with single pass higher fluence settings. Findings suggest that similar collagen fibril alteration can occur with multiple pass low-energy treatments and single pulse high-energy treatments. The lower fluence multiple pass approach is associated with less patient discomfort, less side effects, and more consistent clinical results.

Histological and ultrastructural evaluation of the effects of a radiofrequency-based nonablative dermal remodeling device: a pilot study.

BACKGROUND: Many light- and laser-based systems are used to reduce cutaneous wrinkles, and some have been shown to stimulate dermal collagen production. Using the ThermaCool TC radiofrequency device to treat bovine tendon and human abdominal skin, we documented the cutaneous effects of a radiofrequency-based system for nonablative treatment. OBSERVATIONS: Electron microscopy of bovine tendon treated at varied heat and cooling settings revealed collagen fibrils with increased diameter and loss of distinct borders as deep as 6 mm. Human skin treated at varied heat and cooling settings and examined by means of routine light microscopy demonstrated no significant changes in the epidermis or dermal ground substance immediately after treatment; there was scattered mild perivascular and periadnexal inflammation. Three and 8 weeks after treatment, no observable changes were noted. Ultrastructural analysis, however, disclosed isolated, scattered areas of collagen fibrils with increased diameter and loss of distinct borders. In addition, Northern blot analysis demonstrated an increase in collagen type I messenger RNA steady-state expression. CONCLUSIONS: Our findings suggest that collagen fibril contraction occurs immediately after treatment and gives rise to tissue contraction and thermally mediated wounding, which induces new collagen production.

Purkinje cell size is reduced in cerebellum of patients with autism.

1. The authors' goal was to compare the size and density of Purkinje cells in the cerebellum of subjects with and without autism. Blocks of cerebellum were dissected at autopsy from the brains of age, sex- and postmortem-intervaled (PMI) groups of autistic and normal control individuals (N = 5 per group). Frozen, unfixed blocks were sectioned and stained with 1% cresyl violet. 2. The linear, molecular, granular densities and cross-sectional area of Purkinje cells were measured using computer-assisted image analysis. The average cross-sectional areas of Purkinje cells of the patients with autism were smaller by 24% when compared to the normal subjects. Two of the five autistic subjects had mean Purkinje cell sizes that corresponded to greater than 50% reduction in size. There was a substantial effect size difference in Purkinje cell size (eta2 = 0.29) between control and autistic brains (F(1, 8) = 3.32, P = 0.106). No differences in Purkinje cell densities were observed between the two groups 3. These data indicate the possibility of Purkinje cell atrophy in autism with significant neurohistological heterogeneity among individuals diagnosed with this disorder.

Prenatal viral infection leads to pyramidal cell atrophy and macrocephaly in adulthood: implications for genesis of autism and schizophrenia.

We investigated the role of maternal exposure to human influenza virus (H1N1) in C57BL/6 mice on Day 9 of pregnancy on pyramidal and nonpyramidal cell density, pyramidal nuclear area, and overall brain size in Day 0 neonates and 14-week-old progeny and compared them to sham-infected cohorts. Pyramidal cell density increased significantly (p < 0.0038) by 170% in Day 0 infected mice vs. controls. Nonpyramidal cell density decreased by 33% in Day 0 infected progeny vs. controls albeit, nonsignificantly. Pyramidal cell nuclear size decreased significantly (p < 0.0465) by 29% in exposed newborn mice vs. controls. Fourteen-week-old exposed mice continued to show significant increases in both pyramidal and nonpyramidal cell density values vs. controls respectively (p < 0.0085 E1 (exposed group 1), p < 0.0279 E2 (exposed group 2) pyramidal cell density; p < 0.0092 E1, p < 0.0252 E2, nonpyramidal cell density). By the same token, pyramidal cell nuclear size exhibited 37-43% reductions when compared to control values; these were statistically significant vs. controls (p < 0.04 E1, p < 0.0259 E2). Brain and ventricular area measurements in adult exposed mice also showed significant increases and decreases respectively vs. controls. Ventricular brain ratios exhibited 38-50% decreases in exposed mice vs. controls. While the rate of pyramidal cell proliferation per unit area decreased from birth to adulthood in both control and exposed groups, nonpyramidal cell growth rate increased only in the exposed adult mice. These data show for the first time that prenatal exposure of pregnant mice on Day 9 of pregnancy to a sublethal intranasal administration of influenza virus has both short-term and long-lasting deleterious effects on developing brain structure in the progeny as evident by altered pyramidal and nonpyramidal cell density values; atrophy of pyramidal cells despite normal cell proliferation rate and final enlargement of brain. Moreover, abnormal corticogenesis is associated with development of abnormal behavior in the exposed adult mice.