Daylight photodynamic therapy with MAL cream for large-scale photodamaged skin based on the concept of 'actinic field damage': recommendations of an international expert group.

Conventional PDT (c-PDT) is a widely used and approved non-invasive treatment for actinic keratosis (AK). Recent clinical, histological and immunohistochemical observations have shown that c-PDT with methyl aminolevulinate (MAL) may also partially reverse the signs of photodamage. However, pain and the need for special light source equipment are limiting factors for its use, especially in the treatment of large areas. More recently, daylight PDT (DL-PDT) has been shown to be similar to c-PDT in the treatment of AK, nearly painless and more convenient to perform. To establish consensus on recommendations for the use of MAL DL-PDT in patients with large-scale photodamaged skin. The expert group was comprised of eight dermatologists. Consensus was developed based on the personal experience of the experts in c-PDT and DL-PDT, and results of an extensive literature review. MAL DL-PDT for large areas of photodamaged skin was evaluated and recommendations based on broad clinical experience were provided. As supported by evidence-based data from multicentre studies conducted in Australia and Europe, the authors defined the concept of 'actinic field damage' which refers to photodamage associated with actinic epidermal dysplasia, and provide comprehensive guidelines for the optimal use of DL-PDT in the treatment of actinic field damage. The authors concluded that MAL DL-PDT has a similar efficacy to c-PDT at 3-month (lesion complete response rate of 89% vs. 93% in the Australian study and 70% vs. 74% in the European study (95% C.I. = [-6.8;-0.3] and [-9.5;2.4] respectively) and 6-month follow-ups (97% maintenance of complete lesion response) in the treatment of AKs. The authors agree that DL-PDT is not only efficacious but also nearly pain-free and easy to perform, and therefore results in high patient acceptance especially for the treatment of areas of actinic field damage.

Changes in cerebral oxidative metabolism in patients with acute liver failure.

Acute liver failure patients with a persistence of hyperammonemia are at an increased risk of intracranial hypertension due to development of brain oedema. In vitro studies of brain tissue and cell cultures that indicates that exposure to ammonium inhibits enzymatic activity in the tricarboxylic acid cycle, induces substrate depletion through marked glutamate utilization for glutamine synthesis and leads to mitochondrial dysfunction. In patients with acute liver failure cerebral microdialysis studies show a linear correlation between the lactate to pyruvate ratio and the glutamine concentration, as well as to some of the adenosine triphosphate degradation products. However, clinical observations of cerebral exchange rates of oxygen, glucose, lactate and amino acids challenge the interpretation of these findings. In this review the conflicting data of cerebral metabolism during acute liver failure is discussed.

Guidelines on the safety of light-based home-use hair removal devices from the European Society for Laser Dermatology.

In the past 5 years since their US introduction, there has been a rapid proliferation of light-based hair removal devices intended for home-use. In the last 2 years in Europe, sales already run into many tens of thousands of units with well-known multi-national companies entering the market. These guidelines provide a definition of light-based home-use technology, to inform healthcare professionals about home-use light-based technology and encourage manufacturers wishing to sell in Europe to adopt 'best practice'. The review presents the current status on standards and regulation issues and considers home-use safety issues, encompassing human, device and electrical safety, given risks to the eyes and skin from optical radiation both to the consumer and persons in the vicinity. Proposed technical measurement methodology is considered with focus on recognized critical parameters for the safe use of light-based hair removal technology including recording the technical performance and safety claims of a range of home-use hair removal devices. The literature review emphasizes potential adverse incidents and safety aspects of treating cosmetic conditions, such as unwanted hair growth. Although some regulations exist, they differ from region to region and there is a specific need for international common principles and guidelines relating to the manufacture, marketing and use of intense pulsed light and laser devices, including manufacturing standards for home-use products intended, amongst others, for cosmetic hair removal and photo-rejuvenation procedures. In these guidelines, the European Society for Laser Dermatology (ESLD) provides a professional view of what 'best practice' may imply for manufacturers and consumers alike.

A systematic review of light-based home-use devices for hair removal and considerations on human safety.

BACKGROUND: Hair removal with professional light-based devices is established as an effective, mainstream treatment. The field of optical home-based hair removal is evolving and movement from control by physicians into hands of consumers warrants understanding efficacy and human safety. OBJECTIVES: To systematically review and evaluate the efficacy and human safety of currently available home-based optical hair removal devices. METHODS: A comprehensive Pub Med literature search was conducted which systematically identified publications of relevance. Prospective clinical trials were included whether controlled, uncontrolled or randomized and with a sample size of at least 10 individuals. RESULTS: We identified a total of seven studies: one controlled (CT) and six uncontrolled trials (UCTs). No randomized controlled trials (RCT) were recognized. The best evidence was found for IPL (intense pulsed light) (three devices, one CT, five UCTs) and limited evidence for laser devices (one diode laser, one UCT). Most studies evaluated short-term hair reduction up to 3 and 6 months following light exposure at different body sites. Hair reduction percentages ranged from 6% to 72% after repetitive treatments. The most frequently reported side-effect was erythema, but oedema, blistering, crusting and pigment changes were also reported. Theoretical concerns about ocular damage and paradoxical hair growth have not been reported in any of the studies reviewed. CONCLUSIONS: Available evidence from prospective, uncontrolled clinical trials indicates short-term hair removal efficacy of currently available home-use light-based hair removal devices. Additional controlled trials will be helpful to substantiate the efficacy and to better predict the incidence of adverse events associated with optical home-use hair removal.

Treatment of vitiligo with khellin liposomes, ultraviolet light and blister roof transplantation.

BACKGROUND: Various surgical and non-surgical methods are available to treat vitiligo. Surgical techniques such as epidermal blister graft transplantation may be effective for the re-pigmentation of stable, but refractory vitiligo areas. Khellin has phototherapeutic properties that are similar to those of the psoralens, but with substantially lower phototoxic effects and DNA mutation effects. Its penetration into the hair follicles is enhanced by encapsulating it into liposomes. Subsequent activation of the khellin with UV light stimulates the melanocytes in the hair follicles. OBJECTIVE: The first objective was to evaluate the additional value of combining blister roof transplantation (BRT) with khellin in liposomes and ultraviolet light (KLUV) in the treatment of recalcitrant vitiligo patches. The second objective was to assess patients' satisfaction. MATERIALS AND METHODS: Nineteen patients with vitiligo lesions which did not respond to KLUV treatment for at least a year were treated with BRT followed by KLUV. The transplantation was performed by creating blisters with a suction device, preparing the target site with Erbium laser ablation and the actual transplantation. Locations where randomly assigned. A blinded observer established the results. RESULTS: Seventy-five percent of the patients were satisfied with the cosmetic result. All of the patients would recommend the treatment to other vitiligo patients. More than 75% re-pigmentation of the vitiligo areas was noted in 47% of the patients according to the blinded evaluation of photographs taken before and after the treatment.

Photodynamic therapy of acne vulgaris using 5-aminolevulinic acid 0.5% liposomal spray and intense pulsed light in combination with topical keratolytic agents.

BACKGROUND: Increasing antibiotic resistance of Propionibacterium acnes and growing awareness on the side effects of topical and systemic drugs in the treatment of acne vulgaris by physicians and patients have paved the way for a search into new efficacious and safe treatment modalities such as photodynamic therapy (PDT). Although the efficacy of PDT using 20% 5-aminolevulinic acid (ALA) cream has been established, phototoxic side effects limit its use. The 5-ALA concentration can be lowered by a factor of 40 by changing the vehicle of 5-ALA from a moisturizing cream to liposome encapsulation. OBJECTIVES: Assessment of the efficacy and the safety of PDT using 5-ALA 0.5% in liposomal spray and intense pulsed light (IPL) in combination with topical peeling agents (Li-PDT-PC) in acne vulgaris. MATERIALS AND METHODS: 32 patients suffering from acne participated in this randomized, prospective, single blind study. All patients were treated with Li-PDT-PC. During the study nine patients were additionally treated with topical or systemic antibiotics (Li-PDT-PC-AT). These patients were removed from the study although their results were recorded. Results After a mean period of 7.8 months and a mean number of 5.7 treatments the mean total number of lesions dropped from 34.6 lesions to 11.0 lesions, resulting in a mean improvement of 68.2%. Side effects were minimal. Additionally, an intention to treat analysis was conducted. CONCLUSION: Photodynamic therapy of acne vulgaris using 5-ALA 0.5% liposomal spray and IPL in combination with topical peeling agents is safe and efficacious, even in patients with acne recalcitrant to standard therapy.

Liposomes in dermatology today.

Liposomes are vesicles consisting of spherical phospholipid bi-layers with specific properties making them useful for topical application of drugs. Liposome research has expanded considerably over the last 30 years and nowadays, it is possible to construct a wide range of liposomes varying in size, phospholipids composition and surface characteristics to suit the specific application for which they are intended. In dermatology, the topical application of liposomes has proven to be of therapeutic value. Liposomes can be used as carriers for hydrophilic as well as lipophilic therapeutic agents because of their amphipathic character. They may improve stabilization of instable drugs by encapsulating them and serve as penetration enhancers facilitating the transport of compounds that otherwise cannot penetrate the skin. Liposomes help in reducing skin irritation by sustaining the release of drugs and by hydration of the epidermis. They also have the potential to target drugs into the pilosebaceous structures and hence they have an additional advantage for treatment of hair follicle-associated disorders. Clinical data indicate that 5-ALA encapsulated in liposomes improves the quality of Fluorescence Diagnosis by ALA-induced Porphyrins (FD) and optimizes the results of Photodynamic Therapy (PDT).

Ablative versus non-ablative treatment of perioral rhytides. A randomized controlled trial with long-term blinded clinical evaluations and non-invasive measurements.

BACKGROUND AND OBJECTIVE: To compare efficacy and side effects of CO(2) laser resurfacing and intense pulsed light (IPL) rejuvenation for treatment of perioral rhytides. METHODS: Twenty-seven female subjects with perioral rhytides (class I-III) were randomly treated with either CO(2) laser or IPL (three monthly treatments). Efficacy was evaluated by patient self-assessments and blinded photographs up to 12 months postoperatively. Side effects were assessed clinically. Non-invasive measurements included: trans epidermal water loss (TEWL), skin reflectance, skin elasticity, and ultrasound. RESULTS: CO(2) laser resurfacing resulted in higher degrees of patient satisfaction and clinical rhytide reduction compared to IPL rejuvenation up to 12 months postoperatively (patient evaluations, P < 0.05) (observer evaluations, P < 0.008). Laser-induced side effects included erythema, dyspigmentation, and milia whereas no side effects were observed after IPL rejuvenation. Non-invasive measurements showed a significant higher reduction of the subepidermal low-echogenic band in CO(2) laser treated areas versus IPL treated areas (12 months postoperatively, P < 0.001). Skin elasticity (expressed as Young's modulus) increased in both groups (P = ns). One month postoperatively a significant increase in TEWL values (P < 0.009) and skin redness% (P < 0.02) was found in CO(2) laser treated patients versus IPL treated patients. No significant differences were seen in skin pigmentation% during the observation period. CONCLUSION: CO(2) laser resurfacing induces a significantly higher degree of clinical rhytide reduction followed by considerably more side effects compared to IPL rejuvenation in a homogeneous group of patients.

Cutaneous immunological activation elicited by a low-fluence pulsed dye laser.

BACKGROUND: Three years ago, the nonablative wrinkle reduction laser (a 585-nm laser, Chromogenex V3; Chromogenex Light Technologies, Llanelli, U.K.) was developed, and there have already been several reports about its clinical effectiveness. The Chromogenex V3 laser has also been reported to be effective in treating acne and atopic dermatitis. These results suggest that the Chromogenex V3 laser has some immunological role. In this study, we investigated immunological changes elicited by laser irradiation at the ultrastructural level and by analysis of interleukin (IL)-2 and IL-4 mRNA in skin homing T lymphocytes. MATERIALS AND METHODS: Eight healthy adult volunteers (mean age 56.3 years, range 25-66 years) were recruited for this study. Ultrastructural analysis was done 3 h after the laser irradiation, as well as 1 day, 3 days, 1 week, 2 weeks, 4 weeks and 5 weeks later. IL-2 and IL-4 mRNAs in skin homing T cells cultured for 6 weeks were semiquantitatively measured using reverse transcriptase-polymerase chain reaction. RESULTS: Ultrastructural observations revealed that at 3 h after laser therapy, neutrophils, monocytes and mast cells could already be seen in the extravascular dermis. These dermal acute inflammatory changes were observed also at 1 week after laser treatment. Two weeks after laser treatment, the capillaries showed an almost normal structure. Four weeks after laser treatment, many lymphocytes and fibroblasts were observed. The numbers of these lymphocytes increased further at 5 weeks after the laser treatment. One week after the laser irradiation, all subjects were positive for IL-2 mRNA and for IL-4 mRNA. The level of IL-4 mRNA was larger compared with that of IL-2 mRNA in all subjects. CONCLUSION: The Chromogenex V3 is a 585-nm visible light laser, and it may affect the skin not only by selective photothermolysis but also by direct cutaneous immunological activation.

Intense pulsed light source for the treatment of dye laser resistant port-wine stains.

OBJECTIVE: The purpose of this clinical study was to evaluate the efficacy of an intense pulsed light (IPL) irradiator system for the treatment of port-wine stains (PWS) resistant to multiple pulsed dye laser (PDL) treatments. MATERIALS AND METHODS: Fifteen PWS patients, who were previously found to be resistant to multiple PDL treatments, were treated four times with a second generation IPL system. The clinical efficacy was evaluated on close-up photographs 2 months after the last treatment. RESULTS: Patients with dye laser resistant PWS could be divided into two groups: responders to IPL treatments (46.7%) and non-responders(53.3%). All responders obtained more than 50% reduction, and 85.7% of the responders obtained between 75% and 100% reduction of their lesions. The group of non-responders was defined as patients who obtained less than 25% clearance. CONCLUSIONS: Approximately half of a group of PWS patients, who did not respond to previous PDL treatments, obtained good or excellent clinical effect after four treatments with the IPL system. All PWS, except those located in the V2 area of the face, responded to the treatments. The IPL treatment modality was found to be safe and efficient for the treatment of PWS, except for those located in the V2 area.

Skin reactions to histamine of healthy subjects after hypnotically induced emotions of sadness, anger, and happiness.

BACKGROUND: The severity of symptoms in asthma and other hypersensitivity-related disorders has been associated with changes in mood but little is known about the mechanisms possibly mediating such a relationship. The purpose of this study was to examine the influence of mood on skin reactivity to histamine by comparing the effects of hypnotically induced emotions on flare and wheal reactions to cutaneous histamine prick tests. METHODS: Fifteen highly hypnotically susceptible volunteers had their cutaneous reactivity to histamine measured before hypnosis at 1, 2, 3, 4, 5, 10, and 15 min after the histamine prick. These measurements were repeated under three hypnotically induced emotions of sadness, anger, and happiness presented in a counterbalanced order. Skin reactions were measured as change in histamine flare and wheal area in mm2 per minute. RESULTS: The increase in flare reaction in the time interval from 1 to 3 min during happiness and anger was significantly smaller than flare reactions during sadness (P<0.05). No effect of emotion was found for wheal reactions. Hypnotic susceptibility scores were associated with increased flare reactions at baseline (r=0.56; P<0.05) and during the condition of happiness (r=0.56; P<0.05). CONCLUSION: Our results agree with previous studies showing mood to be a predictor of cutaneous immediate-type hypersensitivity and histamine skin reactions. The results are also in concordance with earlier findings of an association between hypnotic susceptibility and increased reactivity to an allergen.

Experimental pain and psychologic status of patients with chest pain with normal coronary arteries or ischemic heart disease.

BACKGROUND: The cause of chest pain in patients with a normal coronary angiogram (NCA) remains an enigma. Also, it is unclear whether psychosocial factors play a role in the etiology of chest pain in these patients. The objective of the current study was to compare psychosocial factors, clinical pain, and responses to experimental pain in NCA patients, patients with ischemic heart disease (IHD), and healthy control subjects. METHODS: Pain intensity, threshold, and tolerance to cold pressor pain were assessed in 30 NCA patients, 30 IHD patients, and 30 healthy control subjects matched for age, sex, and sociodemographic factors. All subjects completed questionnaires measuring a number of psychosocial factors, including stress, anxiety, depression, extroversion, and neuroticism. NCA and IHD patients also completed questionnaires assessing clinical pain responses and pain-coping strategies. RESULTS: With the exception of a lower tolerance to cold pressor pain of IHD patients (P <.05), no significant differences were found between NCA and IHD patients with respect to other clinical pain measures, psychosocial measures, pain-coping strategies, and other pain-related behaviors. Healthy control subjects differed significantly (P <.05) from both IHD and NCA patients with respect to maximum cold pressor pain, depression, and state anxiety and from IHD patients with respect to intensity of cold pressor pain, threshold to cold pressor pain, and perceived stress. CONCLUSIONS: The results suggest that higher scores on various psychosocial measures in both chest pain groups are related to their pain, rather than being the cause of pain, and do not support a psychogenic explanation for chest pain in the presence of normal coronary arteries.

Intense pulsed light source for treatment of facial telangiectasias.

OBJECTIVE: The purpose of this clinical study was to evaluate the effectiveness of the first intense pulsed light source (IPL) with dual mode light filtering for treatment of facial telangiectasias, and to evaluate the incidence of adverse including purpura, pigmentation and scars. MATERIALS AND METHODS: Twenty-four patients with facial telangiectasias were treated between one and four times with a new IPL system. This system differs from previous IPLs by eliminating wavelengths longer than 950 nm, which would otherwise lead to non-specific heating of tissue water. The treatments were performed at one-month intervals. Two months after the last treatment, the clinical effect was evaluated from close-up photographs. RESULTS: After one to four IPL treatments (mean: 2.54; SD: 0.96) for facial telangiectasias, 79.2% of the patients obtained a more than 50% reduction in number of vessels, and 37.5% obtained between a 75% and 100% reduction. Moderate erythema and oedema were the only adverse effects of the treatment. No purpura was registered and no long-term adverse effects such as scars or pigmentary disturbances occurred. CONCLUSIONS: An IPL with dual mode filtering is efficient and safe for treatment of facial telangiectasias.

Locobase repair cream following CO2 laser skin resurfacing reduces interstitial fluid oozing.

BACKGROUND: The cosmetic result after laser resurfacing depends not only on the type of laser and the technique used, but also on post-treatment care. The efficacy of Locobase Repair((R)) cream, which improves skin barrier function due to its content of natural skin analogue fats and cholesterol, was investigated. METHODS: A total of 18 Caucasian patients underwent resurfacing for acne scars. Laser treatment was performed with a Sharplan 1020 CO(2) laser and a Silk Touch scanner. Locobase Repair cream (a water-in-oil cream with 63% lipids including natural components of stratum corneum: cholesterol, ceramide and free fatty acids) was applied daily to one side of the face and petrolatum was applied to the other. In addition, both sides were treated with a 2% fusidic acid cream. RESULTS: There was a significant reduction of oozing during the first 2 days after CO(2) laser treatment on the sides treated with Locobase Repair cream (p < 0.05), CO(2) laser while from day 3 to day 7 no differences were demonstrated between the Locobase Repair cream and petrolatum. For the other parameters scored (scaling, oedema, erythema and pain), no significant differences between Locobase Repair cream and petrolatum were found. Furthermore, no significant differences were found between the two creams regarding the duration of wound healing and final cosmetic outcome. In all, 62% of the patients preferred to use Locobase Repair cream during the postoperative period, and 11% preferred petrolatum. The remaining 27% expressed no preferences. CONCLUSION: The use of Locobase Repair cream as a post laser resurfacing treatment reduces tissue fluid oozing during the first 2 postoperative days, indicating a quick restoration of skin barrier and hence possibly a reduction in the incidence of wound infections as well as enhancing patient compliance due to less fluid oozing.

[Treatment of tinnitus with low-intensity laser]. / Behandling af tinnitus med lavenergi-laser.

UNLABELLED: This study evaluated the effect of low-power laser in the treatment of tinnitus in a randomized, prospective, double-blind, placebo-controlled trial. The active laser applied 50 mW (cw, 830 nm) over a period of 10 minutes per session. Forty-nine patients were included. The main outcome was measured using psychoacoustical match of tinnitus loudness, Visual Analog Scale (VAS) ratings of subjective loudness, annoyance and attention involved, scores on tinnitus-specific questionnaires, and a number of psychosocial questionnaires. Only few subjects (18%) experienced subjective improvement. There were no statistically significant differences between the effects of the active laser and placebo treatments. CONCLUSION: Low-power laser treatment is not indicated in the treatment of tinnitus. Reports of significant benefits of this treatment in previous studies may be explained by the placebo effect.

Autonomic and psychological responses to an acute psychological stressor and relaxation: the influence of hypnotizability and absorption.

This study examined the influence of hypnotizability and absorption on psychological and autonomic responses to an experimental stressor and a relaxation procedure of 13 high and 13 low hypnotizable subjects. Heart-rate variability was the measure of autonomic reactivity. Absorption was found to be the only significant predictor of autonomic reactivity in both experimental conditions. Expectation and previous relaxation training, but not absorption or hypnotizability, predicted perceived relaxation in the relaxation condition. The results suggest that in a nonhypnotic context the influence of hypnotizability on responses to experimental conditions may be less prominent than the influence of absorption. Absorption may be associated with greater awareness of internal physical and psychological processes, and the results support previous clinical findings of positive correlations between absorption, subjective perception of autonomic arousal, and somatic symptom reporting.

Oesophageal manometry and video-radiology in patients with systemic sclerosis: a retrospective study of its clinical value.

The aim of this retrospective study was to evaluate the initial video-radiology and manometry in 40 consecutive patients with systemic sclerosis (n=21) or suspected systemic sclerosis (n = 19) in relation to oesophageal symptoms; and, furthermore, to evaluate the consequence of radiographic or manometric findings in the oesophagus on diagnosis and treatment. Evaluating oesophageal abnormalities in relation to diagnosis and treatment has, to our knowledge, not been reported before. Video-radiology together with manometry demonstrated oesophageal dysfunction in 80% of patients. Thirteen patients (33%) were asymptomatic in spite of identified motility abnormalities. Following the radiographic and manometric investigation, 9 patients (23%) had a change of diagnosis and, in 20 patients (50%), systemic treatment was instituted or intensified. The study confirms that both manometry and video-radiology are important for the identification of oesophageal motility abnormalities in patients with systemic sclerosis. Oesophageal symptom profiles alone do not predict abnormal findings.

Reliability and validity of a Danish adaptation of the Tinnitus Handicap Inventory.

The objective of this study was to determine the reliability and validity of a Danish translation of the Tinnitus Handicap Inventory (THI), a self-report measure of perceived tinnitus handicap. The Danish version of the THI was administered to 50 patients reporting tinnitus as their primary complaint or secondary to hearing loss. Construct validity was assessed using tinnitus symptom rating scales, the Beck Depression Inventory (BDI), the State-Trait Anxiety Inventory (STAI), the Tinnitus Coping Style Questionnaire (TCSQ), the Eysenck Personality Questionnaire (EPQ), and perceived tinnitus loudness and pitch. The Danish translation of the THI and its subscales showed good internal consistency reliabilities (c = 0.93 to alpha = 0.74) comparable to those of the original version. High to moderate correlations were observed between THI and psychological distress, tinnitus symptom ratings, neuroticism and maladaptive tinnitus coping. A confirmatory factor analysis failed to validate the three subscales of THI, and high intercorrelations found between the subscales question whether they represent three distinct factors. The results suggest that the Danish THI-Total scale may be a reliable and valid measure of general tinnitus related distress that can be used in a clinical setting to quantify the impact of tinnitus on daily living.