Laser-induced thermal coagulation enhances skin uptake of topically applied compounds.

BACKGROUND: Ablative fractional laser (AFL) generates microchannels in skin surrounded by a zone of thermally altered tissue, termed the coagulation zone (CZ). The thickness of CZ varies according to applied wavelength and laser settings. It is well-known that AFL channels facilitate uptake of topically applied compounds, but the importance of CZ is unknown. METHODS: Franz Cells were used to investigate skin uptake and permeation of fluorescent labeled polyethylene glycols (PEGs) with mean molecular weights (MW) of 350, 1,000, and 5,000 Da. Microchannels with CZ thicknesses ranging from 0 to 80 µm were generated from micro-needles (0 µm, CZ-0), and AFL (10,600 nm) applied to -80°C deep frozen skin (20 µm, CZ-20) and skin equilibrated to room temperature (80 µm, CZ-80). Channels penetrated into similar mid-dermal skin depths of 600-700 µm, and number of channels per skin area was similar. At 4 hours incubation, skin uptake of PEGs into CZ and dermis was evaluated by fluorescence microscopy at specific skin depths of 150, 400, and 1,000 µm and the transcutaneous permeation was quantified by fluorescence of receptor fluids. RESULTS: Overall, the highest uptake of PEGs was reached through microchannels surrounded by CZ compared to channels with no CZ (CZ-20 and CZ-80>CZ-0).The thickness of CZ affected PEG distribution in skin. A thin CZ-20 favored significantly higher mean fluorescence intensities inside CZ areas compared to CZ-80 (PEG 350, 1,000, and 5,000; P < 0.001). In dermis, the uptake through CZ-20 channels was significantly higher than through CZ-80 and CZ-0 at all skin depths (PEG 350, 1,000 and 5,000, 150-1,000 µm; P < 0.001). Correspondingly, transcutaneous permeation of PEG 350 was highest in CZ-20 compared to CZ-80 and CZ-0 samples (P < 0.001). Permeation of larger molecules (PEG 1,000 and PEG 5,000) was generally low. CONCLUSION: Uptake of topical compounds is higher through microchannels surrounded by a CZ than without a CZ. Moreover, CZ thickness influences PEG distribution, with highest PEG uptake achieved from microchannels surrounded by a thin CZ. Lasers Surg. Med. 49:582-591, 2017. © 2017 Wiley Periodicals, Inc.

Trends of Stroke Incidence from 1995 to 2013 in Joinville, Brazil.

BACKGROUND: Temporal trends on the incidence of stroke and its subtypes could help assess on-going public health policies and point to further targets for action among middle- and low-income countries, where the stroke burden is very high. This study aimed at evaluating longitudinal trends of stroke incidence in Joinville, Brazil. METHODS: We ascertained the incidence of all first-ever strokes occurred in 1995, 2005-2006 and 2012-2013, which were extracted from Joinville Stroke Registry, a prospective epidemiological data bank, launched in 1995. RESULTS: From 1995 to 2013, the age-adjusted incidence of all strokes decreased 37% (95% CI 32-42). From 2005 to 2013, the haemorrhagic stroke (HS) incidence decreased 60% (95% CI 13-86), ischemic stroke (IS) incidence decreased 15% (95% CI 1-28), and subarachnoid haemorrhage incidence remained stable. The proportion of IS and HS patients with regularly treated hypertension increased by 60% (p = 0.01) and 33% (p = 0.01), respectively. The proportion of IS and HS patients that quit smoking increased 8% (p = 0.03) and 17% (p = 0.03), respectively. CONCLUSIONS: Stroke incidence has been decreasing in Joinville over the last 18 years, more so for HS than IS. Better control of hypertension and tobacco use might explain these findings.

Fractional laser-assisted drug delivery: Laser channel depth influences biodistribution and skin deposition of methotrexate.

BACKGROUND AND OBJECTIVE: Ablative fractional laser (AFXL) facilitates delivery of topical methotrexate (MTX). This study investigates impact of laser-channel depth on topical MTX-delivery. MATERIALS AND METHODS: MTX (1% [w/v]) diffused for 21 hours through AFXL-exposed porcine skin in in vitro Franz Cells (n = 120). A 2,940 nm AFXL generated microscopic ablation zones (MAZs) into epidermis (11 mJ/channel, MAZ-E), superficial-dermis (26 mJ/channel, MAZ-DS), and mid-dermis (256 mJ/channel, MAZ-DM). High performance liquid chromatography (HPLC) was used to quantify MTX deposition in full-thickness skin, biodistribution profiles at specific skin levels, and transdermal permeation. Fluorescence microscopy was used to visualize UVC-activated MTX-fluorescence (254 nm) and semi-quantify MTX distribution in skin. RESULTS: AFXL increased topical MTX-delivery (P < 0.001). Without laser exposure, MTX-concentration in full-thickness skin was 0.07 mg/cm(2) , increasing sixfold (MAZ-E), ninefold (MAZ-DS), and 11-fold (MAZ-DM) after AFXL (P < 0.001). Deeper MAZs increased MTX-concentrations in all skin layers (P < 0.038) and favored maximum accumulation in deeper skin layers (MAZ-E: 1.85 mg/cm(3) at 500 µm skin-level vs. MAZ-DM: 3.75 mg/cm(3) at 800 µm, P = 0.002). Ratio of skin deposition versus transdermal permeation remained constant, regardless of MAZ depth (P = 0.172). Fluorescence intensities confirmed MTX biodistribution through coagulation zones and into surrounding skin, regardless of thickness of coagulation zones (6-47 µm, P ≥ 0.438). CONCLUSION: AFXL greatly increases topical MTX-delivery. Deeper MAZs deliver higher MTX-concentrations than superficial MAZs, which indicates that laser channel depth may be important for topical delivery of hydrophilic molecules. Lasers Surg. Med. 48:519-529, 2016. © 2016 Wiley Periodicals, Inc.

Novel methods for generating fractional epidermal micrografts.

BACKGROUND: Epidermal suction blister grafts are an effective treatment for chronic wounds or vitiligo, but this treatment is time consuming and limited to small areas. OBJECTIVES: To compare two novel strategies to create fractional epidermal grafts. METHODS: Epidermal blisters were raised from fresh human skin ex vivo at 38-40 °C, with suction of 380-510 mmHg. In Strategy 1, a 1-cm blister was micromeshed into approximately 500 pieces, transferred to elastic adhesive dressing, then pneumatically expanded to approximately nine times the original blister area. In Strategy 2, a 25-cm(2) array of 100 small blisters was raised, simultaneously harvested and captured directly onto an adhesive dressing. Measurements were taken for the pneumatic expansion limit, the release of microblisters upon hydration of the dressing adhesive, light microscopy, epidermal cell viability and positive L-3,4 dihydroxyphenylalanine melanocyte presence in blisters. RESULTS: Both strategies yielded viable fractional epidermal microblister arrays, carried on a dressing for transfer to graft recipient sites. The microblisters were gradually released upon hydration of the dressing adhesive. Strategy 2 has major advantages as only small blisters are made at the donor site, skilful dissection and physical expansion are not required and the strategy can be scaled to create large-area grafts. CONCLUSIONS: Strategy 2 is the more practical method for fractional epidermal micrografting to treat larger lesions with less donor-site trauma and has recently been commercialized.

Fractional laser-mediated photodynamic therapy of high-risk basal cell carcinomas--a randomized clinical trial.

BACKGROUND: Photodynamic therapy (PDT) is approved for selected nodular basal cell carcinomas (nBCC) but efficacy is reduced for large and thick tumours. Ablative fractional lasers (AFXL) facilitate uptake of methyl aminolaevulinate (MAL) and may thus improve PDT outcome. OBJECTIVES: To evaluate efficacy and safety of AFXL-mediated PDT (AFXL-PDT) compared with conventional PDT of high-risk nBCC. METHODS: Patients with histologically verified facial nBCC (n = 32) defined as high-risk tumours were included; diameter > 15 mm, tumours located in high-risk zones, or on severely sun-damaged skin. Tumours were debulked and patients randomized to either AFXL-PDT (n = 16) or PDT (n = 16). Fractional CO2 laser treatment was applied at 5% density and 1000 µm (80 mJ) ablation depth. MAL was applied under occlusion for 3 h and illuminated with a 633-nm light-emitting diode source, 37 J cm(-2) . Clinical assessments were performed at 3, 6, 9 and 12 months and biopsies were taken at 12 months. RESULTS: Clinical cure rates at 3 months were 100% (16 of 16 AFXL-PDT) and 88% (14 of 16 PDT, P = 0·484). Recurrences tended to occur later and in lower numbers after AFXL-PDT at 6, 9 and 12 months (6%, 19%, 19%) than PDT (25%, 38%, 44%) (P = 0·114). Histology at 12 months documented equal tumour clearance after AFXL-PDT (63%, 10 of 16) and PDT (56%, 9 of 16). Cosmetic outcomes were highly satisfactory after both treatments (P > 0·090). CONCLUSIONS: Long-term efficacy was similar after PDT and AFXL-PDT with a trend for a favourable short-term cure rate after AFXL-PDT. AFXL-PDT needs further refinement for nBCC and at present is not recommended over PDT.

Transient ischemic attack incidence in joinville, Brazil, 2010: a population-based study.

BACKGROUND AND PURPOSE: There are scarce data on transient ischemic attack incidence in low- and middle-income countries. We aimed to measure transient ischemic attack incidence and the distribution of the ABCD2 risk score in Joinville, Brazil. METHODS: In 2009 to 2010, using a multiple overlapping sources, we ascertained all first ever probable and definite transient ischemic attacks. RESULTS: We recorded 74 definite and probable transient ischemic attacks. The crude incidence was 15 (12-18) per 100 000 population. Age adjusted to European population the incidence was 28 (22-35). One fourth was in the higher risk of stroke by the ABCD2 scale. CONCLUSIONS: The transient ischemic attack incidence in Joinville, Brazil, is lower than other well-designed studies. New studies could clarify whether the measured rates were due to underascertainment or reflect a truly low incidence.

Intensified photodynamic therapy of actinic keratoses with fractional CO2 laser: a randomized clinical trial.

BACKGROUND: Photodynamic therapy (PDT) with methyl aminolaevulinate (MAL) is effective for thin actinic keratoses (AKs) in field-cancerized skin. Ablative fractional laser resurfacing (AFXL) creates vertical channels that facilitate MAL uptake and may improve PDT efficacy. OBJECTIVES: To evaluate efficacy and safety of AFXL-assisted PDT (AFXL-PDT) compared with conventional PDT in field-directed treatment of AK. METHODS: Fifteen patients with a total of 212 AKs (severity grade I-III) in field-cancerized skin of the face and scalp were randomized to one treatment with PDT and one treatment with AFXL-PDT in two symmetrical areas. Following curettage of both treatment areas, AFXL was applied to one area using 10 mJ per pulse, 0·12 mm spot, 5% density, single pulse (UltraPulse(®), DeepFx handpiece; Lumenis Inc., Santa Clara, CA, U.S.A.). MAL cream was then applied under occlusion for 3 h and illuminated with red light-emitting diode light at 37 J cm(-2). Fluorescence photography quantified protoporphyrin IX (PpIX) before and after illumination. RESULTS: At 3-month follow-up, AFXL-PDT was significantly more effective than PDT for all AK grades. Complete lesion response of grade II-III AK was 88% after AFXL-PDT compared with 59% after PDT (P = 0·02). In grade I AK, 100% of lesions cleared after AFXL-PDT compared with 80% after PDT (P = 0·04). AFXL-PDT-treated skin responded with significantly fewer new AK lesions (AFXL-PDT n = 3, PDT n = 11; P = 0·04) and more improved photoageing (moderate vs. minor improvement, P = 0·007) than PDT-treated skin. Pain scores during illumination (6·5 vs. 5·4; P = 0·02), erythema and crusting were more intense, and long-term pigmentary changes more frequent from AFXL-PDT than PDT (P = not significant). PpIX fluorescence was higher in AFXL-pretreated skin [7528 vs. 12,816 arbitrary units (AU); P = 0·003] and photobleached to equal intensities after illumination (AFXL-PDT 595 AU, PDT 454 AU; P = 0·59). CONCLUSIONS: AFXL-PDT is more effective than conventional PDT for treatment of AK in field-cancerized skin.

The Brazilian Family Health Program and secondary stroke and myocardial infarction prevention: a 6-year cohort study.

OBJECTIVES: We compared the incidence of recurrent or fatal cardiovascular disease in patients using Brazil's government-run Family Health Program (FHP) with those using non-FHP models of care. METHODS: From 2005 to 2010, we followed outpatients discharged from city public hospitals after a first ever stroke for stroke recurrence and myocardial infarction, using data from all city hospitals, death certificates, and outpatient monitoring in state-run and private units. RESULTS: In the follow-up period, 103 patients in the FHP units and 138 in the non-FHP units had exclusively state-run care. Stroke or myocardial infarction occurred in 30.1% of patients in the FHP group and 36.2% of patients in non-FHP care (rate ratio [RR] = 0.85; 95% confidence interval [CI] = 0.61, 1.18; P = .39); 37.9% of patients in FHP care and 54.3% in non-FHP care (RR = 0.68; 95% CI = 0.50, 0.92; P = .01) died. FHP use was associated with lower hazard of death from all causes (hazard ratio [HR] = 0.58; P = .005) after adjusting for age and stroke severity. The absolute risk reduction for death by all causes was 16.4%. CONCLUSIONS: FHP care is more effective than is non-FHP care at preventing death from secondary stroke and myocardial infarction.

Education level explains differences in stroke incidence among city districts in Joinville, Brazil: a three-year population-based study.

BACKGROUND: Current evidence suggests an inverse association between socioeconomic status and stroke incidence. Our aim was to measure the variation in incidence among different city districts (CD) and their association with socioeconomic variables. METHODS: We prospectively ascertained all possible stroke cases occurring in the city of Joinville during the period 2005-2007. We determined the incidence for each of the 38 CD, age-adjusted to the population of Joinville. By linear regression analysis, we correlated incidence data with mean years of education (MYE) and mean income per month (MIPM). RESULTS: Of the 1,734 stroke cases registered, 1,034 were first-ever strokes. In the study period, the crude incidence in Joinville was 69.5 per 100,000 (95% confidence interval, 65.3-73.9). The stroke incidence among CD ranged from 37.5 (22.2-64.6) to 151.0 per 100,000 (69.0-286.6). The stroke incidence was inversely correlated with years of education (r = -0.532; p < 0.001). MYE and MIPM were strongly related (R = 0.958), resulting in exclusion of MIPM by collinearity. CONCLUSIONS: Years of education can explain a wide incidence variation among CD. These results may be useful to guide the allocation of resources in primary prevention policies.

Enhanced uptake and photoactivation of topical methyl aminolevulinate after fractional CO2 laser pretreatment.

BACKGROUND AND OBJECTIVES: Photodynamic therapy (PDT) of thick skin lesions is limited by topical drug uptake. Ablative fractional resurfacing (AFR) creates vertical channels that may facilitate topical PDT drug penetration and improve PDT-response in deep skin layers. The purpose of this study was to evaluate whether pre-treating the skin with AFR before topically applied methyl aminolevulinate (MAL) could enable a deep PDT-response. MATERIALS AND METHODS: Yorkshire swine were treated under general anesthesia with a fractional CO(2) laser using stacked single pulses of 3 milliseconds, 91.6 mJ per pulse and subsequent topical MAL application for 3 hours (Metvix®). Red light (LED arrays) was then delivered at fluences of 37 and 200 J/cm(2). Fluorescent photography and microscopy was used to quantify MAL-induced porphyrin distribution and PDT-induced photobleaching at the skin surface and five specific depths down to 1,800 µm. RESULTS: Laser-ablated channels were approximately 1,850 µm deep, which significantly increased topical MAL-induced porphyrin fluorescence (hair follicles, dermis, P < 0.0001) and PDT response, both superficially and deep, versus topical MAL application alone. The fraction of porphyrin fluorescence lost by photobleaching was slightly less after 37 J/cm(2) than after 200 J/cm(2) (overall median values 67-90%; 37 vs. 200 J/cm(2), P > 0.05 for all but one comparison). Photobleaching was steady throughout skin layers and did not vary significantly with skin depth at either LED fluence (P > 0.05). CONCLUSIONS: AFR greatly facilitates topical MAL-induced porphyrins and the fraction of photobleached porphyrins is similar for superficial and deep skin. These observations are consistent with AFR-enhanced uptake of MAL, increased porphyrin synthesis, and photodynamic activation of deep porphyrins even at the lower fluence of 37 J/cm(2), widely used in clinical practice. AFR appears to be a clinically practical means for improving PDT deep into the skin. Clinical studies are suggested to evaluate selectivity in targeting dysplastic cell types.

The Effect of Reconnection to Mechanical Ventilation for 1 Hour After Spontaneous Breathing Trial on Reintubation Among Patients Ventilated for More Than 12 Hours: A Randomized Clinical Trial.

BACKGROUND: The resting of the respiratory musculature after undergoing the spontaneous breathing trial (SBT) to prevent extubation failures in critically ill patients needs to be studied further. RESEARCH QUESTION: Is the reconnection to mechanical ventilation (MV) for 1 h after a successful SBT able to reduce the risk of reintubation? STUDY DESIGN AND METHODS: Randomized clinical trial conducted in four ICUs between August 2018 and July 2019. Candidates for tracheal extubation who met all screening criteria for weaning were included. After achieving success in the SBT using a T-tube, the patients were randomized to the following groups: direct extubation (DE) or extubation after reconnection to MV for 1 h (R1h). The primary outcome was reintubation within 48 h. RESULTS: Among the 336 patients studied (women, 41.1%; median age, 59 years [interquartile range, 45-70 years]), 12.9% (22/171) in the R1h group required reintubation within 48 h vs 18.2% (30/165) in the DE group (risk difference, 5.3 [95% CI, -2.49 to 13.12]; P = .18). No differences were found in mortality, length of ICU or hospital stay, causes of reintubation, or signs of extubation failure. A prespecified exploratory analysis showed that among the 233 patients (69.3%) who were ventilated for more than 72 h, the incidence of reintubation was 12.7% (15/118) in the R1h group compared with 22.6% (26/115) observed in the DE group (P = .04). INTERPRETATION: Reconnection to MV after a successful SBT, compared with DE, did not result in a statistically significant reduction in the risk of reintubation in mechanically ventilated patients. Subgroup exploratory findings suggest that the strategy may benefit patients who were ventilated for more than 72 h, which should be confirmed in further studies. TRIAL REGISTRY: Brazilian Clinical Trials Registry; No.: RBR-3x8nxn; URL: www.ensaiosclinicos.gov.br.

Selective photothermolysis: precise microsurgery by selective absorption of pulsed radiation.

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.

Electron Plasma Oscillations Associated with Type III Radio Bursts.

Plasma wave electric field measurements with the solar orbiting Helios spacecraft have shown that intense (approximately 10 millivolts per meter) electron plasma oscillations occur in association with type III solar radio bursts. These observations confirm the basic mechanism, proposed in 1958, that type III radio emissions are produced by intense electron plasma oscillations excited in the solor corona by electrons ejected from a solar flare.

Spectral character of sunlight modulates photosynthesis of previtamin D3 and its photoisomers in human skin.

The photosynthesis of previtamin D3 from 7-dehydrocholesterol in human skin was determined after exposure to narrow-band radiation or simulated solar radiation. The optimum wavelengths for the production of previtamin D3 were determined to be between 295 and 300 nanometers. When human skin was exposed to 295-nanometer radiation, up to 65 percent of the original 7-dehydrocholesterol content was converted to previtamin D3. In comparison, when adjacent skin was exposed to simulated solar radiation, the maximum formation of previtamin D3 was about 20 percent. Major differences in the formation of lumisterol3, and tachysterol3 from previtamin D3 were also observed. It is concluded that the spectral character of natural sunlight has a profound effect on the photochemistry of 7-dehydrocholesterol in human skin.

Photosynthesis of previtamin D3 in human skin and the physiologic consequences.

Photosynthesis of previtamin D3 can occur throughout the epidermis in the dermis when hypopigmented Caucasian skin is exposed to solar ultraviolet radiation. Once previtamin D3 is formed in the skin, it undergoes a temperature-dependent thermal isomerization that takes at least 3 days to complete. The vitamin D-binding protein preferentially translocates the thermal product, vitamin D3, into the circulation. These processes suggest a unique mechanism for the synthesis, storage, and slow, steady release of vitamin D3 from the skin into the circulation.

Intravenous rtPA versus mechanical thrombectomy in acute ischemic stroke: A historical cohort in Joinville, Brazil.

Groundbreaking results concerning ischemic stroke (IS) hyperacute treatment worldwide were published in 2014 and 2015. We aimed to compare functional status after 3 months in patients treated with intra-arterial thrombectomy (IAT) and those treated with intravenous thrombolysis (IVT) alone in Joinville, Brazil. From the Joinville Stroke Registry, we extracted and compared all consecutive IVT patients treated with r-tPA within 4.5 h in the period 2009-2011 versus all consecutive IAT treated within 6 h with the Solitaire FR device plus IVT in the period 2012-2014. We registered 82 patients in the IVT group and 31 patients in the IAT group. At hospital admission, patients in the IAT group were significantly younger (p < 0.001), had a higher educational level (p = 0.001), had a slightly higher prevalence of atrial fibrillation (p = 0.057) and had more severe strokes measured by the NIH stroke scale (p = 0.011). After 90 days, 45% of patients in the IAT group and 27% in the IVT group were independent (0-1 points) according to the modified Rankin scale (adjusted odds ratio: 4.53; 95% CI: 1.22 to 16.75). Symptomatic hemorrhage was diagnosed in 10% of patients in both groups (p = 1.0). The 90-day case-fatality was 39% (32/82) in the IVT group and 26% (8/31) in the IAT group (p = 0.27). In this small cohort, a greater rate of functional independence was achieved in patients treated with IAT plus IVT, compared with patients treated with IVT lysis alone. Our "real-world" findings are consistent with results of controlled, randomized clinical trials.

Ablative fractional laser alters biodistribution of ingenol mebutate in the skin.

Topically applied ingenol mebutate (IngMeb) is approved for field-treatment of actinic keratosis and is currently being investigated for treatment of non-melanoma skin cancer (NMSC). Ablative fractional lasers (AFXLs) generate microscopic ablation zones (MAZs) in the skin, which may help induce a deep penetration needed for effective treatment of NMSC. Using Franz diffusion cells, uptake and bio-distribution were investigated over 21 h in intact (n = 9) and AFXL-exposed porcine skin (n = 58). A 2940-nm fractional Er:YAG laser generated intraepidermal (11.2 mJ/MAZ; 66 µm deep, 177 µm wide) and intradermal (128 mJ/MAZ; 570 µm deep, 262 wide) MAZ's with 16, 97, and 195 MAZs/cm(2). Surface ablation densities corresponded to 0.5, 2.5, and 5 % for intraepidermal MAZs, and corresponded to 1, 5, and 10.5 % for intradermal MAZs. Liquid-chromatography-mass-spectrometry quantified deposition of IngMeb in stratum corneum, epidermis, dermis, and receiver chamber. In intact skin, IngMeb readily penetrated to the epidermal layer (1,314 ng, 41 % of the applied IngMeb), while dermal deposition was limited (508 ng, 16 %). In AFXL-exposed skin, a profound dermal deposition of IngMeb was achieved, while less accumulated in SC and epidermis. Uptake depended entirely on laser density; increasing coverage from 0 % to 0.5 %, 1 %, 2.5 %, 5 %, and 10.5 % enhanced dermal uptake 1.6-, 2.1-, 3.1-, 3.4-, and 3.9-fold, respectively (p < 0.0001). Channel depth did not influence drug uptake; at 5 % density, dermal deposition with intraepidermal and intradermal MAZs was analogous (1801 vs. 1744; p = 0.447). In conclusion, IngMeb readily distributes to superficial layers of intact skin, whereas dermal uptake is limited. Independent of channel depth, AFXL enhances dermal drug deposition, providing for customized topical delivery and potential use of IngMeb for treatment of NMSC.

The optics of human skin.

An integrated review of the transfer of optical radiation into human skin is presented, aimed at developing useful models for photomedicine. The component chromophores of epidermis and stratum corneum in general determine the attenuation of radiation in these layers, moreso than does optical scattering. Epidermal thickness and melanization are important factors for UV wavelengths less than 300 nm, whereas the attenuation of UVA (320-400 nm) and visible radiation is primarily via melanin. The selective penetration of all optical wavelengths into psoriatic skin can be maximized by application of clear lipophilic liquids, which decrease regular reflectance by a refractive-index matching mechanism. Sensitivity to wavelengths less than 320 nm can be enhanced by prolonged aqueous bathing, which extracts urocanic acid and other diffusible epidermal chromophores. Optical properties of the dermis are modelled using the Kubelka-Munk approach, and calculations of scattering and absorption coefficients are presented. This simple approach allows estimates of the penetration of radiation in vivo using noninvasive measurements of cutaneous spectral remittance (diffuse reflectance). Although the blood chromophores Hb, HbO2, and bilirubin determine dermal absorption of wavelengths longer than 320 nm, scattering by collagen fibers largely determines the depths to which these wavelengths penetrate the dermis, and profoundly modifies skin colors. An optical "window" exists between 600 and 1300 nm, which offers the possibility of treating large tissue volumes with certain long-wavelength photosensitizers. Moreover, whenever photosensitized action spectra extend across the near UV and/or visible spectrum, judicious choice of wavelengths allows some selection of the tissue layers directly affected.

Cumulative effects of repeated subthreshold doses of ultraviolet radiation.

For fair Caucasian skin, the minimal delayed erythema dose (MED) 24 hr after exposure to broadband UVA is about 1200 times greater than the MED of broadband UVB, for both single and multiple daily exposures. Repeated daily exposure to doses less than MED results in cumulative effects manifest by gradual lowering of the daily dose threshold for delayed erythema and pigmentation induced by UVA or UVB. At threshold doses, UVB is more erythemogenic than melanogenic; the opposite is true for UVA. Repeated daily UVA exposure greatly enhances melanogenesis such that markedly suberythemogenic exposure doses of UVA result in true melanogenesis.

The effect of temperature and other factors on selective microvascular damage caused by pulsed dye laser.

Brief pulses of 577-nm radiation have recently been shown to selectively damage superficial cutaneous blood vessels, resulting clinically in purpura. There was a sharp threshold of exposure dose necessary for causing purpura in any given subject, which correlated with histologic evidence of extravasation and specific vascular injury. As a means of studying mechanisms for such damage, heat, cold, pressure, suction, UV radiation, and intradermal epinephrine were used to alter human cutaneous microvasculature prior to and during 577-nm pulsed dye laser exposures. When compared with control sites, only cooling of the skin significantly affected the exposure dose needed to cause purpura. The magnitude of this effect is quantitatively most consistent with intravascular microvaporization as the cause of vessel rupture and hence purpura.