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Neue Entwicklungen in der Lasertherapie
Abstract
Basierend auf der 1916 von Albert Einstein inaugurierten Theorie der stimulierten Emission von Licht wurden in den 1960er-Jahren die ersten Laser entwickelt. Der erste klinische Einsatz eines Lasers in einer Universitätshautklinik in Deutschland erfolgte 1978 in der Dermatologischen Klinik der Ludwigs-Maximilian-Universität München unter der Leitung des damaligen Direktors, Herrn Prof. Dr. med. Dr. h.c. mult. O. Braun-Falco. Seitdem ist eine rasante Weiterentwicklung der Lasermedizin zu verzeichnen. Heute ist die Lasertechnologie eine interdisziplinär genutzte Therapieform, die insbesondere in der Dermatologie klinisch wie auch wissenschaftlich fest verwurzelt ist. Die Behandlung zahlreicher Indikationen der klassischen und auch der ästhetischen Dermatologie erfolgt heute standardmäßig – teilweise ausschließlich – mittels Lasertechnologie. In der vorliegenden Arbeit soll auf aktuelle Entwicklungen der Lasermedizin eingegangen werden. Hier zeichnet sich in der jüngsten Vergangenheit ein Trend zu Kombinationsbehandlungen ab. Mit dem Ziel der Wirkungsverstärkung werden hierbei verschiedene Lichtsysteme komplementär angewendet oder der Laser mit einer dezidierten Arzneimittelapplikation kombiniert.
Background:
Fibroblasts are the main cells involved in regeneration during wound healing. The objective was to determine the effect of 940 nm diode laser on cultured human fibroblasts using different irradiation regimens.
Methods:
The CCD-1064Sk human epithelial fibroblast cell line was treated with a 940 nm diode laser at different energy doses (power: 0.2-1 W and energy density: 1-7 J/cm²) using different transmission modes (continuous or pulsed). The effect on cell growth at 24 and 72 h post-treatment was examined by measuring the proliferative capacity, the impact on the cell cycle, and the effect on cell differentiation.
Results:
fibroblast proliferative capacity was increased at 24 and 72 h post-treatment as a function of the energy dose. The greatest increase was observed with a power of 0.2 or 0.5 W and energy density between 1 and 4 J/cm²; no difference was observed between continuous and pulsed modes. There were no significant differences in cell cycle between treated groups and controls. α-actin expression was increased by treatment, indicating enhanced cell differentiation.
Conclusion:
The 940 nm diode laser has biostimulating effects on fibroblasts, stimulating proliferative capacity and cell differentiation without altering the cell cycle. Further researches are necessary to explore its potential clinical usefulness in wound healing.
The treatment of leg veins is routinely performed in clinical practice using near infrared (NIR) lasers. However, due to low absorption of NIR light in blood vessels, the clinical results are still suboptimal. The absorption of the NIR light can be significantly increased with intravenous introduction of an indocyanine green (ICG) dye. In this work a mathematical model was used to delineate clinically valid settings for ICG and NIR lasers for the treatment of leg veins.
A finite element commercial package was used to simulate light propagation and absorption and heat generation in a skin-like geometry. The simulations were conducted for 755 nm and 810 nm light wavelengths, which are emitted by alexandrite and diode lasers, respectively. Five different laser settings, six different vessel diameters (0.1-2 mm) and three ICG concentrations (0, 1 or 2 mg/kg body weight (BW)) were used to calculate the temperature field spatial distribution as a function of time.
The diameter of the blood vessels affects the temperature distribution during and following laser irradiation, with and without ICG. Adding 1 or 2 mg/kg bw of ICG will cause significant temperature increase (15-35°C, p ≤ 0.001) in blood vessels with a diameter of 0.1-1 mm and steep temperature gradients in 1.5-2 mm diameter blood vessels.
Intravenous application of ICG at 1-2 mg/kg may improve coagulation of blood vessels with 0.1-1 mm diameter irradiated with either a diode or alexandrite laser. This should be confirmed with clinical trials in the near future.
In the literature, non-ablative fractionated photothermolysis (nFP) is accredited with improvement of wrinkles and scars combined with a reduced downtime. The purpose of this work was to evaluate the impact of a combination laser (1,320/1,440 nm) for nFP on hypertrophic scars, acne scars, and facial wrinkles. Thirty-six patients suffering from hypertrophic scars (n = 7), acne scars (n = 9), and wrinkles (n = 20) were treated using a combination Nd:YAG laser [λ(em) = 1,320 and 1,440 nm, pulse duration: 3-ms single pulse, fluence: 8.0-9.0 J/cm(2) (1,320 nm); 2.0-2.5 J/cm(2) (1,440 nm)]. The appearance of the treated condition was evaluated in a retrospective study by two blinded investigators based on follow-up photographs and by patient self-assessment. The frequency of side-effects was also assessed. Both patients and blinded observers rated the treatment results for hypertrophic scars and acne scars as slight improvement, and for wrinkles as equal as compared to baseline. No serious side-effects were reported. The light device used did not lead to a considerable clinical improvement of hypertrophic scars, acne scars, or wrinkles in this study.
Conventional immunosuppressive drugs have been used effectively to prevent immunologic rejection in organ transplantation. Individuals taking these drugs are at risk, however, for the development and recurrence of cancer. In the present study we show that the new immunosuppressive drug rapamycin (RAPA) may reduce the risk of cancer development while simultaneously providing effective immunosuppression. Experimentally, RAPA inhibited metastatic tumor growth and angiogenesis in in vivo mouse models. In addition, normal immunosuppressive doses of RAPA effectively controlled the growth of established tumors. In contrast, the most widely recognized immunosuppressive drug, cyclosporine, promoted tumor growth. From a mechanistic perspective, RAPA showed antiangiogenic activities linked to a decrease in production of vascular endothelial growth factor (VEGF) and to a markedly inhibited response of vascular endothelial cells to stimulation by VEGF. Thus, the use of RAPA, instead of cyclosporine, may reduce the chance of recurrent or de novo cancer in high-risk transplant patients.
The flashlamp-pumped pulsed dye laser (FPDL) is regarded as the gold standard in the treatment of port wine stains. The purpose of this prospective, intra-individual, comparative clinical study was to investigate whether a frequency-doubled variable pulsed Nd:YAG laser (frequency-doubled Nd:YAG) is equally as safe and effective as established lasers. Forty-three patients with port wine stains were included in the study. Test treatments were performed using the frequency-doubled Nd:YAG laser (532 nm; 4 mm psi; 5-50 ms; 5.5 to 15 J/cm2) versus the FPDL (585 nm; 450 micros; 7 mm psi; 6 J/cm2). After 6 weeks, a full lesional treatment was performed using the device and the parameters showing the best clearance and the fewest side effects. The clearance of the lesions was generally good to fair. With the exception of poor results at 5 ms and 5.5 J/cm2 with the frequency-doubled Nd:YAG laser, there were no significant differences between the two laser devices. Scar formation, nevertheless, occurred in only 3% of the FPDL-treated sites versus up to 18% of the frequency-doubled Nd:YAG sites, increasing with pulse duration. In port wine stains, the FPDL remains the therapy of choice because of the somewhat better results and a lower frequency of side effects, especially scarring.
Complete clearance of port wine stains (PWS) is difficult to achieve, mainly because of the resistance of small blood vessels to laser irradiation. Indocyanine green (ICG)-augmented diode laser treatment (ICG+DL) may overcome this problem.
This pilot study evaluates the feasibility of ICG-augmented diode laser therapy of PWS and compares safety and efficacy of ICG+DL to the flashlamp-pumped pulsed dye laser (FPDL).
In a prospective randomized controlled clinical study, 31 patients with PWS were treated with FPDL (λem =585nm, 6J/cm², 0.45ms pulse duration) and ICG+DL (λem=810nm, 20–50J/cm², 10–25ms pulse duration, ICG-concentration: 2mg/kg b.w.) in a split-face modus that included histological examination (H&E, CD34). Two blinded investigators and the patients assessed clearance rate and cosmetic appearance.
ICG+DL therapy induced photocoagulation of medium and large blood vessels (>20µm diameter) but not of small blood vessels. According to the investigators' assessment, clearance rates and cosmetic appearance were better after ICG+DL therapy than after FPDL treatment (p=0.114, p=0.291), although not up to a statistically significant level, whereas patients considered these parameters superior (p=0.003, p=0.006).
ICG+DL represents a new and promising treatment modality for PWS, but laser parameters and ICG-concentration need to be further optimized.
• Background and Design.—
Anecdotal reports and clinical observations have suggested that the response of port-wine stains to treatment with the pulsed dye laser is variable and dependent on the anatomical location of the lesion. To investigate anatomical variation in response to treatment, a retrospective study of 259 adults and children with port-wine stains of the head and neck treated with the pulsed dye laser was undertaken. Evaluation was performed by comparing simultaneously projected pretreatment and completiontreatment photographs. Anatomical differences in response were evaluated in three ways: (1) by anatomical subdivision of the head and neck into regions, (2) by dermatomal distribution, and (3) by response for midline lesions. The head and neck was subdivided into eight anatomical regions, which were independently evaluated for response. In addition, response for individual dermatomes and for midline lesions was evaluated. Response in all cases was assessed by determining the percentage of lightening from 0% to 100% (where 100% represents complete response) at the completion of treatment. Response grades were also assigned, using grades poor (0% to 25% lightening), fair (26% to 50% lightening), good (51% to 75% lightening), or excellent (76% to 100% lightening).
Results.—
One hundred thirty-seven adults and 122 children were included in the study. Evaluation by subdivision of the head and neck into regions revealed that in adults and children the centrofacial regions (medial aspect of the cheek, upper cutaneous lip, and nose) responded less favorably than the other grouped regions (periorbital, forehead/temple, lateral aspect of the cheek, neck, and chin); the centrofacial regions showed a good response (mean lightening, 70.7%), while the other grouped regions of the head and neck showed an excellent response (mean lightening, 82.3%). Evaluation by dermatomal distribution revealed that dermatome V2 showed a good response (mean lightening of 73.8%), while combined dermatomes V1, V3, and C2/C3 showed an excellent response (mean lightening of 82.4%). Evaluation of midline lesions revealed excellent responses in adults and children (mean lightening, 92.4%).
Conclusions.—
Port-wine stains of the head and neck in adults and children demonstrate differences in response to treatment with the pulsed dye laser according to their anatomical location. Centrofacial lesions and lesions involving dermatome V2 in adults and children respond less favorably than lesions located elsewhere on the head and neck. Midline lesions respond very favorably in adults and children.(Arch Dermatol. 1993;129:182-188)
Editorial comment Therapies that selectively target diseased cells while sparing normal tissue remain the goal of modern medicine. Photodynamic therapy (PDT) achieves double selectivity both by the degree that preferential accumulation of the photosensitizer occurs in the targeted cells and the extent to which the illumination is spatially localized to the target. Dr. GI Stables has reviewed the burgeoning literature on this oxygen-requiring technique by discussing its essential components (photosensitizers, light sources) and its many applications including benign, premalignant, and malignant disease. Most studied has been the use of 5 -aminolaevulinic acid PDT for psoriasis, actinic keratoses and non-melanoma skin cancer. While residents and trainees have reason to be excited about these developments, all readers should be cautioned that PDT's role in routine dermatological practice awaits comparison to carefully controlled trials involving comparison to more standardized techniques.
Background:
Unwanted hair is a widespread cosmetic problem. Many temporary methods of hair removal exist, with laser hair removal rapidly becoming the most widely used modality.
Objectives:
Our objective was to evaluate the efficacy and side effects of a long-pulsed ruby laser for epilation in patients with varying skin types and hair color 6 weeks and 6 months after treatment.
Methods:
Seventy-four patients received one to four treatments with a long-pulsed ruby laser (694 nm, 5-msec pulse length, 6 mm spot size, 17.5-32 J/cm2) in different body areas.
Results:
After a mean number of treatments of 1.98 (range 1-4) the mean clearance was 51-75% after 6 weeks and less than 25% after 6 months. A lower percentage of hair regrowth was observed in the facial region than on the trunk or legs and in dark hair compared to blond hair.
Conclusion:
Laser epilation provides a quick and relatively comfortable, but nonpermanent modality for hair removal with few side effects.
Basic theoretical considerations of the optical and thermal transfer processes that govern the thermal damage induced in tissue by lasers are discussed. An approximate, predictive model and data are proposed for the purpose of selecting a laser that maximizes damage to cutaneous blood vessels and minimizes damage to the surrounding connective tissue and the overlying epidermis. The variables of wavelength, exposure duration, and incident energy density are modeled, and a flashlamp-pumped dye laser operating at or near the 577 nm absorption band of HbO2, with a pulsewidth (0.3 μsec) less than the estimated, approximately 1 millisecond, thermal relaxation times for microvessels is chosen for experimental exposures of normal Caucasian skin. Highly specific laser-induced damage to blood vessels is demonstrated both clinically and histologically. This is in striking contrast to the previously reported widespread, diffuse necrosis caused by other lasers. The incident energy and preliminary observations of wavelength and temperature dependence for vascular damage thresholds are consistent with theoretical predictions. Whereas typically 20 joules/cm2 of argon laser irradiation (514 and 488 nm, ∼100 msec) is required to induce widespread thermal damage, the pulsed dye laser requires only about 2 joules/cm2 to induce highly specific vascular damage. The potential usefulness of dye laser-induced selective vascular damage as a treatment modality for portwine stain hemangiomas and other vascular lesions is discussed. In addition to possible treatment applications, the dye laser or other sources meeting the requirements for producing such damage may also offer a useful experimental tool for inducing predictable damage to microvas-culature. Histopathologic and clinical studies related to these possibilities are in progress.
Telangiectatic leg veins, which affect about 40-50% of adults, represent a frequent cosmetic rather than a medical problem. Besides sclerotherapy, various laser devices are common treatment options. However, complete clearance rates can only be achieved in a small number of patients.
In this proof-of-concept study, the safety and efficacy of indocyanine green (ICG)-augmented diode laser therapy (808 nm) was evaluated for the treatment of telangiectatic leg veins.
ICG (2 mg/kg body weight) was intravenously administered in 15 female patients (skin type II to III) with telangiectatic leg veins (measuring between 0.25 and 3 mm in diameter). Immediately after ICG injection, diode laser pulses with different radiant exposures (50-110 J/cm(2)) were applied as one single treatment. Safety and efficacy were assessed 1 and 3 months after treatment by a blinded investigator and the patient. Treatments with the pulsed dye laser (PDL) and the diode laser without ICG served as reference therapies.
The safety of ICG application and diode laser treatment was excellent in all patients with no persisting side effects. Vessel clearance was dose-dependent. Diode laser treatment at radiant exposures between 100 and 110 J/cm(2) resulted in good vessel clearance, which even improved to excellent after the application of double pulses. Diode laser therapy without ICG and PDL treatment induced poor to moderate clearance of telangiectatic leg veins.
ICG-augmented diode laser therapy has proved to be a safe and effective treatment option for telangiectatic leg veins.
Complete clearance of port-wine stains (PWS) is difficult to achieve, mainly because of the resistance of small blood vessels to laser irradiation. Indocyanine green (ICG)-augmented diode laser treatment (ICG+DL) may overcome this problem.
To evaluate the feasibility of ICG+DL therapy of PWS and to compare the safety and efficacy of ICG+DL with the standard treatment, flashlamp-pumped pulsed dye laser (FPDL).
In a prospective randomized controlled clinical study, 31 patients with PWS were treated with FPDL (λ(em)=585 nm, 6 J cm(-2) , 0.45 ms pulse duration) and ICG+DL (λ(em)=810 nm, 20-50 J cm(-2) , 10-25 ms pulse duration, ICG-concentration: 2 mg kg(-1) body weight) in a split-face modus in one single treatment setting that included histological examination (haematoxylin and eosin, CD34). Two blinded investigators and the patients assessed clearance rate, cosmetic appearance and side-effects up to 3 months after treatment.
ICG+DL therapy induced photocoagulation of medium and large blood vessels (>20 μm diameter) but not of small blood vessels. According to the investigators' assessment, clearance rates and cosmetic appearance were better after ICG+DL therapy than after FPDL treatment (P=0.114, P=0.291, respectively), although not up to a statistically significant level, whereas patients considered these parameters superior (P=0.003, P=0.006, respectively). On a 10-point scale indicating pain during treatment, patients rated ICG+DL to be more painful (5.81 ± 2.12) than FPDL treatment (1.61 ± 1.84).
ICG+DL represents a new and promising treatment modality for PWS, but laser parameters and ICG concentration need to be further optimized.
Vitiligo is a common acquired depigmentation disorder caused by the loss of melanocytes. Despite the numerous treatment modalities available for vitiligo, responses to treatment are still unsatisfactory. For this reason, new treatment modalities and approaches are needed.
To investigate the effects of fractional carbon dioxide (CO(2) ) laser therapy followed by systemic narrowband ultraviolet B (NB-UVB) phototherapy on nonsegmental vitiligo (NSV) as a prospective and randomized left-right comparative study.
Ten patients with NSV who presented symmetrical vitiligo lesions with no further improvement despite more than 1 year of conventional treatment were enrolled. Two sessions of half-body fractional CO(2) laser therapy were performed at a 2-month interval. NB-UVB phototherapy was then administered to the entire body 5 days after each fractional laser treatment twice a week, increasing the dose incrementally by 15% at each session. Objective clinical assessments were made by two blinded dermatologists using a quartile grading scale, and the patients' overall satisfaction was evaluated using a 10-point visual analogue scale.
Two months after the last treatment, mean improvement scores, assessed by physicians, were significantly higher for those treated with half-body fractional CO(2) laser therapy followed by NB-UVB phototherapy, compared with those treated with NB-UVB alone (P=0·034). In addition, according to subjective assessment, the half-body laser treatment followed by NB-UVB showed significantly higher improvements compared with NB-UVB treatment alone (P=0·023). Noticeable adverse events, such as infection, scarring and Koebner phenomenon, were not found in any patient.
This study suggests that fractional CO(2) laser therapy followed by NB-UVB phototherapy could be used effectively and safely as an alternative modality for the treatment of refractory vitiligo.
Several laser technologies exist for improving rhytides, pigmentation, and skin texture. Recent advances in technology introduced a new wavelength, 2,790 nm, erbium:yttrium-scandium-galium-garnet (Er:YSGG) for treatment of photoaging. 2,790 nm Er:YSGG has a water absorption coefficient between CO(2) laser and Er:YAG laser and has both ablative and fractional-ablative capabilities.
To evaluate the efficacy and safety of combining the ablative (confluent) and fractional-ablative modes of 2,790 nm Er:YSGG laser for treatment of photoaging.
In this uncontrolled, open label, prospective study, 10 subjects were enrolled and had a single treatment of combined confluent and fractional-ablative 2,790 nm lasers for photoaging. The primary clinical end point of the study was the change in Fitzpatrick wrinkle score from baseline at different time points as determined by blinded reviewer assessments. Secondary clinical end points were the improvement in fine lines, tone/texture, and pigmentation; the subjects' self assessment; the incidence of side effects; and the tolerability of treatments.
Based on blinded photo-assessments by two independent dermatologists, subjects showed clinically and statistically significant mean improvement of 1.9 (95% CI: 1.1-2.6), 1.6 (95% CI: 0.8-2.3), and 1.2 (95% CI: 0.5-2.0) in Fitzpatrick wrinkle scores at 6 weeks, 3 and 6 months, respectively. Of the 90% of subjects who showed improvement in Fitzpatrick wrinkle scores, 78% continued to have improvement at the 6-month follow-up visit. Mild erythema observed post-treatment was resolved by the 6-week follow-up visit in all subjects. No transient or permanent post-inflammatory hyperpigmentation (PIH); or serious adverse events were reported.
A combined confluent and fractional-ablative 2,790 nm Er:YSGG laser treatment improves photodamaged skin for at least 6 months. The treatment was well-tolerated and PIH was not found in our study.
The aim of this study was to evaluate the ability of a low-fluence fractional erbium:yttrim-aluminum-garnet (Er:YAG) laser, with a wavelength of 2940 nm, for enhancing and controlling the skin permeation of imiquimod and macromolecules such as polypeptides and fluorescein isothiocyanate (FITC)-labeled dextran (FD). The in vitro permeation has been determined using a Franz diffusion cell, with porcine skin and nude mouse skin as the barriers. Hyperproliferative and ultraviolet (UV)-irradiated skins were also used as barrier models to mimic the clinical therapeutic conditions. Confocal laser scanning microscopy (CLSM) was used to examine the in vivo nude mouse skin uptake of peptide, FITC, and FD. Both in vitro and in vivo results indicated an improvement in permeant skin delivery by the laser. The laser fluence and number of passes were found to play important roles in controlling drug transport. Increases of 46- and 127-fold in imiquimod flux were detected using the respective fluences of 2 and 3 J/cm(2) with 4 pulses. An imiquimod concentration of 0.4% from aqueous vehicle with laser treatment was sufficient to approximate the flux from the commercial cream with an imiquimod dose of 5% without laser treatment, indicating a reduction of the drug dose by 125-fold. The enhancement of peptide permeation was size and sequence dependent, with the smaller molecular weight (MW) and more-hydrophilic entities showing greater enhancing effect. Skin permeation of FD with an MW of at least 150 kDa could be achieved with fractional laser irradiation. CLSM images revealed intense green fluorescence from the permeants after exposure of the skin to the laser. The follicular pathway was significant in laser-assisted permeation.
Port-wine stains (PWS) are congenital, progressive vascular malformations of the dermis that are often disfiguring, particularly when located in a cosmetically relevant area. Thus, the successful clearance of PWS is of highest medical relevance, and laser therapy is the treatment of choice for this indication. Numerous trials have shown the effectiveness of both lasers and incoherent light sources. Laser or IPL treatments achieve good clearance in the majority of PWS, but complete clearance is rare. Thus, new therapeutic options are urgently required. Photodynamic therapy is a relatively new approach in the treatment of PWS. Our review aims to summarize therapy options of port-wine stains, depending on treatment area, patient age, and vessel architecture. Recent developments in this field and new insights into the pathogenesis of PWS are discussed. The review also highlights practical aspects, complications that can occur, and how to prevent them.
A handpiece with a 35 × 22-mm treatment window that uses vacuum technology has been designed for the diode laser system. Vacuum suction stretches the skin and brings the hair follicle closer to the surface with the intent to damage the hair follicle at a lower surface fluence. The objective of this study was to compare the degree of follicular thermal damage between the sapphire-cooled smaller handpiece at a higher fluence versus the larger vacuum-assisted handpiece at a lower fluence.
Five male patients with Fitzpatrick skin types I-IV were enrolled in the study. Three test spots on the right back were treated with the vacuum-assisted laser handpiece at a setting of 10-12 J/cm², and 61-ms pulse duration. Three test spots on the left back were treated with the sapphire-cooled handpiece with a setting of 30-34 J/cm² and a pulse duration of 14-16 ms. A punch biopsy was obtained from one treated area for each handpiece type. The biopsies were sectioned horizontally and examined for the degree of thermal damage to the hair follicle at the level of the isthmus and the bulb. Immediate treatment response, pain score, and total treatment time were recorded.
Biopsies from the skin treated with the sapphire-cooled handpiece and the vacuum-assisted handpiece showed the mean hair follicle diameter was 258.3 µm (SE [standard error] 41.7) and 225.1 µm (SE 17.1), respectively. The mean thermal damage diameter to hair diameter ratio was 0.91 (SE 0.10) and 0.72 (SE 0.12), respectively. The mean immediate treatment response, the mean pain severity, and the mean total treatment time were all lower for the vacuum-assisted handpiece.
Treatment with the vacuum-assisted handpiece is faster and has a tendency to be more comfortable. Thermal damage to the hair follicle was greater with the sapphire-cooled handpiece.
Leg telangiectasias have been reported to have been treated with a variety of lasers. This study was designed to measure response to treatment of leg telangiectasias with a unique coupled 585 nm and 1064 nm pulse.
Sixty female patients (24-62 y.o., skin types II-IV) with leg vein varicosities were treated with pulses of a combined 585 nm long pulsed dye (LPDL) and 1064 nm Nd:YAG lasers, which were delivered sequentially using a novel dual laser device. Pulses were placed along the entire length of the targeted veins. A beam diameter of 7 mm with pulses of 10 ms and 9 J/cm² of fluence for LPDL, and pulses of 30 ms and 80 J/cm² for the 106 nm Nd:YAG were utilized and these remained uniform. Time delays between sequential LPDL and Nd:YAG pulses were 125 ms, 250 ms and 500 ms depending on vein diameter of 4, 3 and 2 mm respectively. One or two treatments were given at 2 month intervals, with post-treatment assessments at 6 months following the final treatment. Patients subjectively assessed the treatment and their results were used to draw up a satisfaction index (SI). Objective assessment was based on clinical photography and computer-generated data using a vein clearance detection computer program.
The overall patient satisfaction rate was 47 of 60 patients and the objective assessments, based on blinded evaluation of clinical photography as well as computer assessment, demonstrated good to very good improvement in 47 by photograph evaluation and 49 of 60 patients by computer edge detection data.
The combination of LPDL and Nd:YAG laser pulses offered efficient treatment of leg veins irrespective of skin type. Results were better on blue and vessels larger than 1 mm. Side effects were minimal and transient.
In dermatology, topical photodynamic therapy (PDT) is a well established treatment modality which has mainly shown to be effective for dermato-oncologic conditions like actinic keratosis, Bowen's disease, in-situ squamous cell carcinoma and superficial basal cell carcinoma. However, a therapeutical benefit of PDT is also evident for inflammatory dermatoses like localized scleroderma, acne vulgaris and granuloma annulare as well as for aesthetic indications like photo aged skin or sebaceous gland hyperplasia. Recent work has been focused on the development and evaluation of topical photosensitizers like the hem precursor 5-aminolevulinic acid or its methyl ester inducing photosensitizing porphyrins. These drugs do not induce strong generalized cutaneous photosensitization like the systemically applied porphyrins or their derivatives. For dermatological purposes incoherent lamps or LED arrays can be used for light activation. Depending on the applied light dose and the concentration of the photosensitizer either cytotoxic effects resulting in tumor destruction or immunomodulatory effects improving the inflammatory conditions occur. Treating superficial oncologic lesions (tumor thickness < 2-3 mm) cure rates achieved by PDT are equal to the cure rates of the respective standard therapeutic procedure. The benefits of PDT are the low level of invasiveness and the excellent cosmetic results after treatment.
So far, pulsed dye lasers have been regarded as the gold standard in the treatment of port-wine stains (PWS). Recently, intense pulsed light (IPL) has been reported to achieve more pronounced fading in some patients.
To evaluate the efficacy and the side effects of IPL treatment of PWS in a direct comparison to the short-pulsed dye laser (SPDL) and the long-pulsed dye laser (LPDL).
Test spots (n = 158) were applied with IPL (λ(em) = 555-950 nm, pulse duration: 8-14 milliseconds (single pulse), fluence: 11-17.3 J/cm(2)), the SPDL (λ(em) = 585 nm, pulse duration: 0.45 milliseconds, fluence: 6 J/cm(2)), and the LPDL (λ(em) = 585/590/595/600 nm, pulse duration: 1.5 milliseconds, fluence: 12/14/16/18 J/cm(2)) in a side-by-side modus in untreated (n = 11) and previously treated (n = 14) patients with PWS. Lesion clearance was evaluated by three blinded investigators based on follow-up photographs 6 weeks after treatment. Incidence of side effects was assessed.
In previously untreated PWS as well as in pretreated PWS, IPL treatments were rated significantly (P<0.05) better than treatments with the SPDL. In both groups, IPL and LPDL treatments did not differ significantly. Side effects were few in all settings.
In PWS resistant to dye laser therapy, IPL showed additional lesion clearance. The use of IPL increases the therapeutic possibilities in PWS.
It has been suggested that the adjunctive use of 5-aminolevulinic acid (ALA) with intense pulsed light (IPL), known as ALA-IPL photodynamic therapy (PDT), increases the benefits of IPL therapy for photoaging.
To evaluate the efficacy and safety of ALA-IPL PDT for photoaging in Chinese subjects with Fitzpatrick skin types III and IV.
This was a prospective, controlled, split-face study with 26 subjects. Subjects received three split-face treatments 4 weeks apart. A blinded investigator assessed the signs of photodamage. Satisfaction was also assessed.
Twenty-four subjects completed the trial. Better results were achieved for global score, fine lines, and coarse wrinkles on the PDT/IPL treated side than on the IPL-only side at the final visit (50% vs 12.5%p=.005 for global score, 70.8% vs 33.3%p=.009 for fine lines, 50% vs. 12.5%, p=.005 for coarse wrinkles). Phototoxic reactions such as erythema and edema were the primary side effects, as well as an increase in postinflammatory hyperpigmentation.
ALA-IPL PDT has superior rejuvenation effects over IPL alone in Chinese subjects. Taking reasonable precaution to prevent the postinflammatory hyperpigmentation is the most important point in making ALA-IPL PDT a successful therapy.
5-Aminolaevulinic acid (ALA) is used in photodynamic therapy (PDT). Response rates of PDT vary widely, which may be because of the limited uptake of topically applied photosensitisers. We investigated skin penetration and fluorescence induction of protoporphyrin IX (PpIX) after applying either 20% ALA cream or 20% aminolaevulinic acid solution on laser-stripped stratum corneum (SC) in an ex vivo full-thickness porcine skin model. Both formulations are used in clinical practice. To enhance the skin penetration of ALA, we used two different 2940-nm erbium:yttrium-aluminium-garnet (Er:YAG) laser systems to partially ablate the SC: continuous and fractional ablation. Different fluences were applied ranging from 0.5 to 1.5 J/cm(2) (continuous ablation) and from 4 to 24 J/cm(2) (fractional ablation). Fluorescence microscopy was used for detecting PpIX-induced fluorescence. Compared to skin without laser pretreatment, mean fluorescence intensity (MFI) of PpIX was enhanced 13.8-fold after continuous ablation with 1.0 J/cm(2) and 7.3-fold after fractional ablation with 4 J/cm(2); each laser procedure was followed by 4-h incubation with lipophilic ALA cream. Optimal parameters for continuous ablation without damage to the epidermis were 1 J/cm(2) for both formulations, fractional ablation was best with 4 J/cm(2). Histological evaluations of laser-treated skin showed necrosis and apoptosis, depending on light dose. In laser-stripped skin, PpIX fluorescence was detected earlier and reached deeper epidermal layers than in untreated skin. Continuous laser ablation induced higher PpIX fluorescence levels than fractional ablation. This method offers a promising new tool for enhancing ALA penetration in PDT without damaging the underlying tissue.
Photodynamic therapy (PDT) has become an established treatment modality for dermatooncologic conditions like actinic keratosis, Bowen's disease, in situ squamous cell carcinoma and superficial basal cell carcinoma. There is also great promise of PDT for many non-neoplastic dermatological diseases like localized scleroderma, acne vulgaris, granuloma anulare and leishmaniasis. Aesthetic indications like photo-aged skin or sebaceous gland hyperplasia complete the range of applications. Major advantages of PDT are the low level of invasiveness and the excellent cosmetic results. Here, we review the principal mechanism of action, the current developments in the field of photosensitizers and light sources, practical aspects of topical PDT and therapeutical applications in oncologic as well as non-oncologic indications.
Port-wine stains (PWS) represent a group of vascular malformations that are usually accompanied by psychological distress for affected patients, often reflected in high treatment demand. Although the pulsed-dye laser (PDL) was established as standard therapy for PWS more than a decade ago, therapeutic outcome may be unsatisfactory. One of the main drawbacks to successful PDL therapy is PWS revascularization shortly after laser exposure. Therefore, inhibition of revascularization should improve therapeutic outcome of PDL therapy. In this study, we first evaluated the effects of various light energies on normal cutaneous vessels over a period of 14 days, particularly the proliferation and stem cell marker expression of dermal endothelial cells, which were found to be highest 8 days following laser exposure. We found that PDL exposure induced dose-dependent damage of dermal vessels up to energy densities of 6 J/cm(2), above which no increase in PDL-induced effects were observed with the energies employed in this study. In dermal endothelial cells of PDL-exposed skin, we found strong expression of the proliferation marker Ki-67 as well as the stem cell marker nestin but not other stem cell markers such as CD133 and CD166. The influence of rapamycin (RPM), used as an adjuvant to PDL exposure, was also investigated. RPM administration reduced Ki-67 and nestin expression in dermal endothelial cells and increased PDL-induced destruction of dermal vessels, indicating that the use of RPM after PDL exposure may be an interesting new approach for prolonging and improving PWS laser therapeutic outcome.
High efficacy and safety, coupled with in-office, short contact protocols have made photodynamic therapy (PDT) with aminolevulenic acid (ALA) for the treatment of actinic keratoses a mainstay option over the last decade. Clinical improvement in photoaged skin has also been reported to accompany PDT treatments. The study objective was to maximize epidermal penetration and subsequent activation of ALA for the treatment of photodamaged facial skin, utilizing a microneedle roller prior to incubation and combined irradiation with red light and broadband pulsed light in a single treatment.
A full-face treatment of 21 patients was performed with 630 nm light and broadband pulsed light after multiple passes with a microneedle roller and 1-hour ALA incubation. The primary endpoint was clinical improvement, scored during two separate live assessments by three physicians blinded to previous scores, using a 5-point standardized photoaging scale. The secondary endpoint was evaluation of patient satisfaction based on a quartile scale comparing baseline to 6-month post-treatment photography.
Statistically significant improvement was seen in the global photoaging scores, as well as sub-components of the scale (fine lines, mottled pigmentation, sallowness, tactile roughness, and telangiectasias) at 3 months as compared with baseline live assessment, and at 6-month live assessment compared with the 3 months. In addition, 90% of patients judged clinical improvement to be greater than 50% at 6 months compared to baseline photography.
Use of a microneedle roller to "pre-treat" prior to application of ALA appears to be well tolerated and allows for even absorption and perhaps deeper penetration of ALA following a defined incubation period. Use of red light and broadband pulsed light allowed for deeper activation of ALA, potentially accounting for marked clinical improvement in photoaging.
Complete blanching of port wine stain (PWS) birthmarks after laser therapy is rarely achieved for most patients. We postulate that the low therapeutic efficacy or treatment failure is caused by regeneration and revascularization of photocoagulated blood vessels due to angiogenesis associated with the skin's normal wound healing response. Rapamycin (RPM), an antiangiogenic agent, has been demonstrated to inhibit growth of pathological blood vessels. Our objectives were to (1) investigate whether topical RPM can inhibit reperfusion of photocoagulated blood vessels in an animal model and (2) determine the effective RPM concentration required to achieve this objective.
For both laser-only and combined laser and RPM treated animals, blood vessels in the dorsal window chambers implanted on golden Syrian hamsters were photocoagulated with laser pulses. Structural and flow dynamics of blood vessels were documented with color digital photography and laser speckle imaging to evaluate photocoagulation and reperfusion. For the combined treatment group, topical RPM was applied to the epidermal side of the window daily for 14 days after laser exposure.
In the laser-only group, 23 out of 24 photocoagulated blood vessels reperfused within 5-14 days. In the combined treatment group with different RPM formulae and concentrations, the overall reperfusion rate of 36% was much lower as compared to the laser-only group. We also found that the reperfusion rate was not linearly proportional to the RPM concentration.
With topical RPM application, the frequency of vessel reperfusion was considerably reduced, which implies that combined light and topical antiangiogenic therapy might be a promising approach to improve the treatment efficacy of PWS birthmarks.
Recently, there has been much debate regarding the long-term efficacy of fractional resurfacing devices. While pulsed CO(2) laser resurfacing is considered a highly effective treatment, fractionated resurfacing is a newer modality and its long-term efficacy has yet to be assessed. We report the long-term outcomes of subjects previously treated with fractional CO(2) resurfacing for photodamaged skin and acne scars.
Ten subjects from our previous studies who received fractional resurfacing for the treatment of acne scarring and photodamage returned for long-term follow-up visits at 1 and 2 years, respectively. Investigators graded maintenance of improvement on a quartile scale based on clinical photography.
Subjects maintained 74% of their overall improvement at their long-term visits compared to 3-month follow-up visits. While clinical improvement was maintained long-term, the results were not as remarkable as those seen at 3-month visits. The authors speculate that results seen at 3 months may be enhanced by persistent inflammatory changes, as evidenced by heat shock protein 47 activity and ongoing collagen remodeling seen in previous histologic studies. Relaxation of tightening is to be expected with any procedure along with the natural progression of aging. However, patient satisfaction was upheld long-term.
Fractional CO(2) laser resurfacing does have long-term efficacy and persistence of improvement of acne scarring and photodamage compared to baseline. However, additional treatments may be necessary to enhance long-term results.
Ablative fractional lasers were introduced for treating facial rhytides in an attempt to achieve results comparable to traditional ablative resurfacing but with fewer side effects. However, there is conflicting evidence on how well this goal has generally been achieved as well as on the comparative value of fractional CO(2) and Er:YAG lasers. The present study compares these modalities in a randomized controlled double-blind split-face study design.
Twenty-eight patients were enrolled and completed the entire study. Patients were randomly assigned to receive a single treatment on each side of the peri-orbital region, one with a fractional CO(2) and one with a fractional Er:YAG laser. The evaluation included the profilometric measurement of wrinkle depth, the Fitzpatrick wrinkle score (both before and 3 months after treatment) as well as the assessment of side effects and patient satisfaction (1, 3, 6 days and 3 months after treatment).
Both modalities showed a roughly equivalent effect. Wrinkle depth and Fitzpatrick score were reduced by approximately 20% and 10%, respectively, with no appreciable difference between lasers. Side effects and discomfort were slightly more pronounced after Er:YAG treatment in the first few days, but in the later course there were more complaints following CO(2) laser treatment. Patient satisfaction was fair and the majority of patients would have undergone the treatment again without a clear preference for either method.
According to the present study, a single ablative fractional treatment session has an appreciable yet limited effect on peri-orbital rhytides. When fractional CO(2) and Er:YAG lasers are used in such a manner that there are comparable post-operative healing periods, comparable cosmetic improvement occurs. Multiple sessions may be required for full effect, which cancels out the proposed advantage of fractional methods, that is, fewer side effects and less down time.
Intense pulsed light (IPL) devices use flashlamps and bandpass filters to emit polychromatic incoherent high-intensity pulsed light of determined wavelength spectrum, fluence, and pulse duration. Similar to lasers, the basic principle of IPL devices is a more or less selective thermal damage of the target. The combination of prescribed wavelengths, fluences, pulse durations, and pulse intervals facilitates the treatment of a wide spectrum of skin conditions.
To summarize the physics of IPL, to provide guidance for the practical use of IPL devices, and to discuss the current literature on IPL in the treatment of unwanted hair growth, vascular lesions, pigmented lesions, acne vulgaris, and photodamaged skin and as a light source for PDT and skin rejuvenation.
A systematic search of several electronic databases, including Medline and PubMed and the authors experience on intense pulsed light.
Numerous trials show the effectiveness and compatibility of IPL devices.
Most comparative trials attest IPLs similar effectiveness to lasers (level of evidence: 2b to 4, depending on the indication). However, large controlled and blinded comparative trials with an extended follow-up period are necessary.
Ablative fractional resurfacing (AFR) creates vertical channels that might assist the delivery of topically applied drugs into skin. The purpose of this study was to evaluate drug delivery by CO(2) laser AFR using methyl 5-aminolevulinate (MAL), a porphyrin precursor, as a test drug.
Two Yorkshire swine were treated with single-hole CO(2) laser AFR and subsequent topical application of MAL (Metvix(R), Photocure ASA, Oslo, Norway), placebo cream and no drug. MAL-induced porphyrin fluorescence was measured by fluorescence microscopy at skin depths down to 1,800 microm. AFR was performed with a 10.6 microm wavelength prototype CO(2) laser, using stacked single pulses of 3 millisecond and 91.6 mJ per pulse.
AFR created cone-shaped channels of approximately 300 microm diameter and 1,850 microm depth that were surrounded by a 70 microm thin layer of thermally coagulated dermis. There was no porphyrin fluorescence in placebo cream or untreated skin sites. AFR followed by MAL application enhanced drug delivery with significantly higher porphyrin fluorescence of hair follicles (P<0.0011) and dermis (P<0.0433) versus MAL alone at skin depths of 120, 500, 1,000, 1,500, and 1,800 microm. AFR before MAL application also enhanced skin surface (epidermal) porphyrin fluorescence. Radial diffusion of MAL from the laser-created channels into surrounding dermis was evidenced by uniform porphyrin fluorescence up to 1,500 microm from the holes (1,000, 1,800 microm depths). Skin massage after MAL application did not affect MAL-induced porphyrin fluorescence after AFR.
Ablative fractional laser treatment facilitates delivery of topical MAL deeply into the skin. For the conditions of this study, laser channels approximately 3 mm apart followed by MAL application could produce porphyrins throughout essentially the entire skin. AFR appears to be a clinically practical means for enhancing uptake of MAL, a photodynamic therapy drug, and presumably many other topical skin medications.
Photodynamic therapy (PDT) is a modern therapy modality, based upon the application of a photosensitizing agent like aminolevulinic acid, a physiological precursor of porphyrins, onto the tissue followed by illumination with light of the visible wavelength spectrum. During this oxygen-dependent reaction, reactive oxygen species (ROS) are generated that have immunomodulatory or cytotoxic effects. PDT shows excellent cosmetic results especially for its key indication in dermatology - the treatment of non-melanoma skin cancer. The associated pain and the low tissue penetration are the most frequent limiting factors of PDT. We review basic principles and recent developments in photosensitizers and light sources. Key oncological and non-oncological indications are presented as well.
Repeated exposure to ultraviolet radiation from the sun results in premature photoaging. Photodynamic therapy (PDT) has been shown to be effective for treatment of photoaging, although the data from most studies have been based on clinical observation.
We investigated whether 5-aminolevulinic acid (ALA)-PDT induced histologic changes suggesting photorejuvenation.
Fourteen patients with one to three actinic keratoses on the face were treated twice with ALA-PDT by using a 1200 W metal halogen lamp at 1-month intervals. Skin biopsy before and 1 month after the PDT was performed. Twenty-five pairs of specimens were obtained. We examined the specimens with routine and immunohistochemical staining and evaluated the parameters associated with photoaging by using image analysis.
After ALA-PDT, the mean epidermal thickness and dermal inflammatory infiltrate were reduced. The total collagen volume in the dermis significantly increased with expression of type I and III procollagen. The level of transforming growth factor beta and transforming growth factor beta type II receptors in the epidermis also increased. The elastotic material with co-localizing fibrillin-1 and tropoelastin expression in the dermis decreased after treatment. The expression of matrix metalloproteinases-1, -3, and -12 also decreased.
The study was limited by the small sample size.
ALA-PDT resulted in histological changes indicating restoration of photoaged skin. These data suggest that ALA-PDT could be effective for photorejuvenation.
Treatment of vascular malformations is one of the main indications for laser application in dermatology. The argon laser is suitable for coagulation of superficial lesions, the Nd:YAG laser for thicker ones. Vaporization or excision of vascular lesions can be performed by means of the CO2 laser. International standard of argon laser therapy of port wine stains are 60 to 70% good results in adult patients afflicted with red and purple lesions. In contrast argon laser therapy of pink lesions and of children is less successful. But more recently the flashlamp pumped dye laser has improved treatment results in children, since this laser acts much more vessel specific than the argon laser. Other congenital vascular lesions that respond to laser therapy are capillary hemangiomas, cavernous hemangiomas, and lymphangiomas. Future development may expand application of laser in the treatment of vascular malformations.
Suitably brief pulses of selectively absorbed optical radiation can cause selective damage to pigmented structures, cells, and organelles in vivo. Precise aiming is unnecessary in this unique form of radiation injury because inherent optical and thermal properties provide target selectivity. A simple, predictive model is presented. Selective damage to cutaneous microvessels and to melanosomes within melanocytes is shown after 577-nanometer (3 x 10(-7) second) and 351-nanometer (2 x 10(-8) second) pulses, respectively. Hemodynamic, histological, and ultrastructural responses are discussed.
Basic theoretical considerations of the optical and thermal transfer processes that govern the thermal damage induced in tissue by lasers are discussed. An approximate, predictive model and data are proposed for the purpose of selecting a laser that maximizes damage to cutaneous blood vessels and minimizes damage to the surrounding connective tissue and the overlying epidermis. The variables of wavelength, exposure duration, and incident energy density are modeled, and a flashlamp-pumped dye laser operating at or near the 577 nm absorption band of HbO2, with a pulse width (0.3 microsecond) less than the estimated, approximately 1 millisecond, thermal relaxation times for microvessels is chosen for experimental exposures of normal Caucasian skin. Highly specific laser-induced damage to blood vessels is demonstrated both clinically and histologically. This is in striking contrast to the previously reported widespread, diffuse necrosis caused by other lasers. The incident energy and preliminary observations of wavelength and temperature dependence for vascular damage thresholds are consistent with theoretical predictions. Whereas typically 20 joules/cm2 of argon laser irradiation (514 and 488 nm, approximately 100 msec) is required to induce widespread thermal damage, the pulsed dye laser requires only about 2 joules/cm2 to induce highly specific vascular damage. The potential usefulness of dye laser-induced selective vascular damage as a treatment modality for portwine stain hemangiomas and other vascular lesions is discussed. In addition to possible treatment applications, the dye laser or other sources meeting the requirements for producing such damage may also offer a useful experimental tool for inducing predictable damage to microvasculature. Histopathologic and clinical studies related to these possibilities are in progress.
Two-hundred and fifty-seven patients (136 adults and 121 children) with port-wine stains of the head and neck were treated with the flashlamp-pumped pulsed dye laser. The head and neck was subdivided into 8 anatomical regions (forehead/temple, periorbital, medial cheek, nose, upper cutaneous lip, lateral cheek, chin and neck) which were independently evaluated for response. Response to treatment was found to be associated with the anatomical location of the lesion; in both adults and children the mid-facial region (medial cheek, nose and upper cutaneous lip) responded less favorably to treatment than the other regions of the head and neck (periorbital, forehead/temple, lateral cheek, neck and chin). In adults and children, mean percent lesional lightening of the mid-facial regions was 70.7% compared to 82.3% of the other regions of the head and neck with an estimated difference of 11.6% (95% confidence interval: 8.7% - 14.6%). The mean number of treatments for adults was 3.7, while this number in children was 3.9. All side effects were transient, and included cutaneous depressions, hypopigmentation and hyperpigmentation.
The flashlamp-pumped pulsed dye laser (FPDL) was the first laser system specifically developed for the treatment of cutaneous vascular lesions such as port-wine stains (PWS), telangiectases and haemangiomas. Its theoretical advantages have been verified by numerous excellent clinical results. As there are few systematic studies on the adverse effects of this laser system, we investigated 100 consecutive patients who received FPDL therapy of PWS. Pain during and after laser therapy was a common complaint. Post-treatment erythema occurred in 29%, oedema in 73%, formation of bullae in 1%, and serous crusting in 46-83% of patients (based on our observations and the patients histories, respectively), all of which lasted for a maximum of 7 days. Furthermore, complications such as impetigo-like crusting occurred in 25%, bleeding in 12%, a pyogenic granuloma in 1%, hyperpigmentation in 27%, hypopigmentation in 1%, atrophic scarring in 3%, and an hypertrophic scar in 1%. Although most of these changes were only focal, and were predominantly transient, our results indicate that the incidence of side-effects and complications produced by the FPDL (wavelength 585 nm, pulsewidth 450 microseconds) may be higher than previously documented in the literature.
Preliminary results indicate that pulsed dye lasers (PDL) with 1.5 ms pulsewidth and 595 nm wavelength are effective in the treatment of leg telangiectasia. The aim of this study was to evaluate if the clinical results could be improved by a) an effective skin cooling with ice cubes and b) the longer wavelength of 600 nm.
In 87 patients with vessels up to 1 mm in diameter, 257 single test treatments were performed using wavelengths of 595 and 600 nm, fluences of 16, 18, and 20 J/cm2, a 1.5 ms pulse duration, and an elliptical spot of 2 x 7 mm. In 7 patients, the skin surface temperature curve was measured after cooling with ice cubes vs hydrogel dressings, and spot geometry and fluence were investigated with and without the gel dressing.
Vessel clearance was evaluated 6-8 weeks after treatment. 20 J/cm2 were most effective (80% clearance >50%), and 18 J/cm2 were more effective than 16 J/cm2 (66.2 vs 52.5% clearance >50%). There was a tendency towards better results with 595 nm, but the differences were not significant. Vessels with a diameter <0.5 mm cleared significantly better than those with 0.5-1 mm (69.1 vs 31.9% clearance >50%). Hypo- and hyperpigmentation were seen in 32% of the patients. Cooling with ice cubes proved to be far more effective than with hydrogel dressings (temperature decrease approx 15 vs 5 degrees C). Additionally, the gel dressing caused an energy loss of approx 35% and an irregular spot geometry as shown on burn paper.
Treatment of leg telangiectasia with the 1.5 ms-PDL is safe and effective, especially in vessels smaller than 0.5 mm in diameter; 595 nm and 18 J/cm2 seem to be somewhat more effective as 600 nm and 16 J/cm2; and 20 J/cm2 are even more effective, but persistent hyperpigmentation cannot yet be excluded due to insufficient follow-up time. Cooling with ice cubes is more effective and less expensive than gel dressings, and the short term clinical results are equivalent, even if the frequency of transient pigmentary changes is increased.
Rapamycin in transplantation: A review of the evidence. The calcineurin inhibitors have been the mainstays of immunosuppression for solid organ transplantation over the last two decades, but nephrotoxicity limits their therapeutic benefit. Rapamycin is a new drug with both immunosuppressant and antiproliferative properties that has a unique mechanism of action distinct from that of the calcineurin inhibitors. It has a role as a maintenance immunosuppressant either alone or in combination with a calcineurin inhibitor and can also be used to treat refractory acute rejection. Theoretical evidence suggests that it may limit the development and progression of chronic rejection in transplant recipients, but this has yet to be confirmed. This review examines the current in vitro animal and human work underlying the use of rapamycin and, in addition, comments on the pharmacokinetics and side-effect profile of this promising new agent.
Presenting the long-term results of flashlamp-pumped pulsed dye laser treatment in 617 hemangiomas to evaluate this treatment modality.
In 548 children, 692 hemangiomas were treated with the flashlamp-pumped pulsed dye laser (FPDL) SPTL 1B (Candela Corporation, Wayland, MA). The objective of treatment was the inhibition of further growth or the induction of regression. The treatment results were documented by the treating physician as well as by means of a questionnaire delivered to the parents. A total of 617 treatment results could be evaluated.
After 1--12 treatments (mean, 2.5), we could achieve our treatment objective to stop the further growth of the lesion in 96.6% of all hemangiomas. In 13.8%, the treatment resulted in a complete remission, a significant regression was seen in 14.9%, and 67.9% of the treated lesions showed a discontinuation of growth. The percentage of complete remission was especially high in small superficial (42.6%) and superficial (19%) hemangiomas.
In the vast majority of the hemangiomas, it was possible to stop further progression or induce regression by FPDL treatment. Total regression could be achieved in nearly half of the small superficial hemangiomas. Because the treatment is fast, effective, and nearly without side effects, we recommend early laser treatment especially in superficial and small childhood hemangiomas.
At present, laser therapy of port-wine stains (PWS) using the flashlamp-pumped dye laser (FPDL) at 450 micros is accepted as the optimal approach. A few years ago, a new long-pulsed tunable dye laser (LPTDL, 1.5 ms) was introduced for the treatment of leg veins.
To investigate the efficacy and side-effects of FPDL vs. LPTDL therapy of PWS.
Sixty-two patients with untreated PWS underwent test treatments with the FPDL (585 nm; 7-mm spot size; 5.75--7.0 J cm(-2) fluence) and LPTDL (585, 590, 595, 600 nm; 5-mm spot size; 11--20 J cm(-2) fluence). With the LPTDL, the epidermis was additionally cooled (Spray cooling device). The fading was evaluated clinically 6 weeks after the test treatments.
Optimal fading was achieved by the LPTDL (> or = 585 nm) in 30 patients and by the FPDL in 12 patients. No difference was found in 20 patients. At 585 nm, the lasers worked equally well in 12 (FPDL) and 13 (LPTDL) patients, respectively. Results were independent of the localization of the PWS and of the patient's age. In spite of the longer pulse duration, the LPTDL treatment did not result in more side-effects as long as sufficient cooling was provided.
The results provide evidence that wavelengths longer than 585 nm can increase the efficacy of treatment in some PWS. Owing to the reduced light absorption by haemoglobin at longer wavelengths and consequently increased depth of the vascular injury, larger vessels can be damaged more adequately using an increased fluence. The LPTDL at 585 nm seemed to be slightly superior to the FPDL, while accepting that due to technical reasons the laser parameters were not directly comparable. Availability of both lasers increases the therapeutic possibilities in PWS.
The aim was to investigate the efficacy, side effects, and the long-term results of a long pulsed Nd:YAG-Laser for hair removal in different hair colors and skin types.
We performed a prospective clinical study with 29 volunteers. Treatment was performed on the lower leg with a long pulsed Nd:YAG-Laser. Five test areas were treated 1-5 times in monthly intervals; one served as control. Follow-up investigations were performed at each session, and 3, 6, and 12 months after the last therapy. No depilatory treatment except shaving was allowed during the time of follow-up. Percentual hair loss, short- and long-term side effects, and pain during the treatment were evaluated.
After one month, a hair loss of greater than 50% was found in 44.9% of the areas treated once. With up to five treatments, this percentage increased up to 71.5%. One year after therapy, a greater than 50% hair reduction was still present in 40% of the five-treatment-areas and in 0% of the areas treated only once. There were no permanent side effects despite one small scar after a folliculitis.
The long pulsed Nd:YAG is suitable to remove hair for more than 12 months effectively, although 4-5 sessions are necessary for these results. Blond hair can also be removed, although much less effective. No lasting side effects could be seen. Darker skin types or tanned skin can also be treated without side effects. A cooling may be advisable due to the pain reported by the volunteers.
The need for repeated treatment of restenosis of a treated vessel remains the main limitation of percutaneous coronary revascularization. Because sirolimus (rapamycin) inhibits the proliferation of lymphocytes and smooth-muscle cells, we compared a sirolimus-eluting stent with a standard uncoated stent in patients with angina pectoris.
We performed a randomized, double-blind trial to compare the two types of stents for revascularization of single, primary lesions in native coronary arteries. The trial included 238 patients at 19 medical centers. The primary end point was in-stent late luminal loss (the difference between the minimal luminal diameter immediately after the procedure and the diameter at six months). Secondary end points included the percentage of in-stent stenosis of the luminal diameter and the rate of restenosis (luminal narrowing of 50 percent or more). We also analyzed a composite clinical end point consisting of death, myocardial infarction, and percutaneous or surgical revascularization at 1, 6, and 12 months.
At six months, the degree of neointimal proliferation, manifested as the mean (+/-SD) late luminal loss, was significantly lower in the sirolimus-stent group (-0.01+/-0.33 mm) than in the standard-stent group (0.80+/-0.53 mm, P<0.001). None of the patients in the sirolimus-stent group, as compared with 26.6 percent of those in the standard-stent group, had restenosis of 50 percent or more of the luminal diameter (P<0.001). There were no episodes of stent thrombosis. During a follow-up period of up to one year, the overall rate of major cardiac events was 5.8 percent in the sirolimus-stent group and 28.8 percent in the standard-stent group (P<0.001). The difference was due entirely to a higher rate of revascularization of the target vessel in the standard-stent group.
As compared with a standard coronary stent, a sirolimus-eluting stent shows considerable promise for the prevention of neointimal proliferation, restenosis, and associated clinical events.
The treatment of larger leg veins with laser or intense pulsed light often shows varying degrees of success and inconsistent clinical response rates. Aim of this study was to evaluate the effectiveness and safety of the 755 nm long pulsed high fluence alexandrite laser in the treatment of larger leg veins.
Twenty female volunteers aged 25-51 years (mean 39) with 0.3-1.3 mm leg telangiectasias received laser treatment, 10 of them with an additional pass done right after the first pass. Their skin type ranged from 1 to 3 (five type 1, seven type 2, eight type 3). After test spots with increasing fluences (40-90 J/cm(2)) to determine the individual safe fluence, the maximum fluence of 90 J/cm(2) could be used in all 20 subjects. The spot size was 3 x 10 mm, a spray cooling system was used with 80 milliseconds spray and delay time, respectively. The number of pulses administered ranged from 30 to 467 per subject (mean 139). The treated area was controlled 1 day, 1 month, and 3 months post-treatment and the side effects were quantified. At each visit, the treatment area was photographed. The percent clearance in the treated areas was scored by two observers. Subject satisfaction was evaluated at the 3 months post-treatment visit.
After 3 months, in all 20 test subjects some clearance was visible. It ranged from low-grade to complete clearance. Most subjects (15 of 20) had a clearance between 26 and 75%. Hyperpigmentation was observed in 15 subjects. Hypopigmentation was seen in two subjects. No edema, no purpura, no erythema, no scarring, no blistering, and no crusts were observed. Mean subject satisfaction score was assessed and all volunteers reported to be "satisfied."
The long pulsed high fluence alexandrite laser is effective and safe in the treatment of leg veins 0.3-1.3 mm in diameter.
Our aim was to determine the most effective treatment parameters for laser-assisted hair removal using long-pulsed Nd:YAG-lasers. 42 volunteers were treated with 1064 nm long-pulsed Nd:YAG-lasers. We used two different laser systems (Lyra XP, Wavelight and Smartepil II Deka-LMS) with various pulse lengths, fluences, and spot sizes. For each parameter, five test areas were treated one to five times at 4-week intervals. Follow-ups were performed 1, 3, 6, and 12 months after the last treatment. Percentual hair loss, side effects, and pain during treatment were evaluated. The average hair reduction 12 months after the last treatment using the Lyra XP was 48%, using the Smartepil II it ranged between 30% and 35%. There were no permanent side effects. Long-pulsed 1064 nm Nd:YAG-lasers are safe and effective for hair reduction. Although the different treatment parameters did not lead to a lot of differing hair reduction 12 months after the last treatment, the laser with the largest spot size and the longest pulse time showed the best results.