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Biomedical subjects

Lesley E Rhodes

Publications and source records attributed to Lesley E Rhodes.

13 recordsLinked to original sources

Psychologic distress in polymorphous light eruption and its relationship to patients' beliefs about their condition.

BACKGROUND: Skin disease can cause psychologic difficulties, but information is lacking on the emotional impact of the common photosensitivity condition, polymorphous light eruption (PMLE). OBJECTIVE: We sought to examine the emotional impact of PMLE, and its relationships with patients' beliefs about their PMLE and health-related variables. METHODS: Patients with PMLE who had attended a hospital dermatology department were mailed the Illness Perception Questionnaire-Revised during the summers of 2002 to 2004. RESULTS: Questionnaires were returned by 150 of 302 patients. Emotional distress attributable to PMLE was found in more than 40% of individuals. The emotional impact of PMLE was principally predicted by patients' beliefs about their condition (>50% of the variance), particularly regarding its consequences, whereas health-related variables played a lesser role. Women associated more severe consequences with their PMLE (z = -2.27, P = .02) and were more emotionally distressed (z = -2.17, P = .03) than men. LIMITATIONS: Hospital-based patients with PMLE may not be representative of the community. CONCLUSIONS: Psychologic factors should receive greater attention in PMLE management.

Adolescent↗

The potential of omega-3 fatty acids in the prevention of non-melanoma skin cancer.

In toto, there is strong circumstantial evidence from both experimental and clinical studies to support a role for omega-3 FA in the prevention of non-melanoma skin cancer (NMSC). In experimental animal studies there is direct evidence that dietary omega-3 FA inhibits ultraviolet radiation (UVR) carcinogenic expression, with regard to both increased tumor latent period and reduced tumor multiplicity. Equivalent levels of omega-6 FA increase UVR carcinogenic expression. Dietary omega-3 FA dramatically reduces the plasma and cutaneous pro-inflammatory and immunosuppressive PGE(2) levels in mice. Dietary omega-6 FA increases prostaglandin E synthase type 2 (PGE(2)) level. Dietary omega-3 FA significantly reduces the inflammatory response and sustains, or enhances, the delayed type hypersensitivity immune response in mice when compared to an equivalent dietary level of omega-6 FA. Supplementary omega-3 FA significantly increases the UVR-mediated erythema threshold in humans. Supplementary omega-3 FA significantly reduces the level of pro-inflammatory and immunosuppressive PGE(2) levels in Ultraviolet B-irradiated human skin.

Animals↗

Histamine is released following aminolevulinic acid-photodynamic therapy of human skin and mediates an aminolevulinic acid dose-related immediate inflammatory response.

Acute skin inflammation occurs following topical aminolevulinic acid-photodynamic therapy (ALA-PDT), but its nature and mediation are ill defined. As we observed an urticarial response, a potential role for histamine was explored. In 13 healthy volunteers, we assessed the time course and dose-response of the acute cutaneous response(s) to ALA-PDT, the impact of H(1) antihistamine blockade, and measured dermal histamine release. An ALA dose series was iontophoresed into ventral forearm skin and exposed to red light. All participants exhibited an immediate urticarial response, both wheal and flare correlating with log ALA dose. Subsequently, a dose-related erythema developed at treatment sites by 3 hours and persisted at 24 hours. H(1) blockade with oral cetirizine doubled the median minimal urticating dose of ALA and reduced the slope of dose-response for wheal and flare, whereas at the highest ALA dose, mean wheal and flare areas reduced by 68 and 60%, respectively. In contrast, cetirizine did not influence the 24 hour minimal phototoxic dose or erythema dose-response. Histamine release after ALA-PDT mirrored the urticarial response, levels peaking within 30 minutes and returning to baseline by 24 hours. Thus, two discrete acute inflammatory responses to topical ALA-PDT occur in human skin; histamine mediates the immediate response, but does not appear involved in the delayed phototoxicity.

Adult↗

Eicosapentaenoic acid and docosahexaenoic acid reduce UVB- and TNF-alpha-induced IL-8 secretion in keratinocytes and UVB-induced IL-8 in fibroblasts.

Omega-3 polyunsaturated fatty acids (n-3 PUFA) inhibit ultraviolet B (UVB)-induced inflammation and other inflammatory states, in vivo. We examined whether this may be mediated by modulation of interleukin (IL)-8, a chemokine pivotal to skin inflammation induced by UVB, in epidermal and dermal cells. We also explored the ability of n-3 PUFA to protect against tumor necrosis factor (TNF)-alpha induction of IL-8, and assessed relative potencies of the principal dietary n-3 PUFA, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Pre-supplementation, both HaCaT keratinocyte and CCD922SK fibroblast cell lines showed dose-responses for UVB-induced IL-8 release (p<0.001), assessed 48 h post-irradiation. Cells were supplemented with > or =90% purified EPA, DHA, oleic acid (OA) or vehicle control, for 4.5 d. EPA and DHA supplements were bioavailable to keratinocytes and fibroblasts. In keratinocytes, EPA and DHA were shown to reduce basal secretion of IL-8 by 66% and 63%, respectively (p<0.05), and UVB-induced levels by 66% and 65% at 48 h after 100 mJ per cm2, respectively, (p<0.01). A similar pattern occurred in fibroblasts, whereas OA had no influence on IL-8 release in either cell line. In addition, TNF-alpha-induced IL-8 secretion by keratinocytes was reduced by 54% and 42%, respectively, by EPA and DHA (p<0.001). Hence both n-3 PUFA inhibit production of UVB- and TNF-alpha-induced IL-8 in skin cells; this may be important in the photoprotective and other anti-inflammatory effects conferred by these agents.

Adult↗

Preventive oncology.

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Anticarcinogenic Agents↗

Photodynamic therapy using topical methyl aminolevulinate vs surgery for nodular basal cell carcinoma: results of a multicenter randomized prospective trial.

BACKGROUND: Photodynamic therapy (PDT) is increasingly used as a noninvasive treatment for nodular basal cell carcinoma (BCC), without a sound evidence base. OBJECTIVE: To compare topical PDT, with the use of the sensitizer methyl aminolevulinate, and standard excision surgery in nodular BCC. DESIGN: Prospective, randomized study. SETTING: University dermatology departments. PATIENTS: A total of 101 adults with previously untreated nodular BCC. INTERVENTIONS: Patients received methyl aminolevulinate PDT (n = 52) or surgery (n = 49). The PDT was given twice, 7 days apart, with methyl aminolevulinate cream (160 mg/g) and 75 J/cm(2) red light (570-670 nm). Thirteen patients with a noncomplete response to PDT at 3 months (24% lesions) were retreated. OUTCOME MEASURES: Primary end point was clinically assessed lesion clearance at 3 months after treatment. Secondary end points were sustained response rate at 12 months and cosmetic outcome at 3 and 12 months. Cosmesis and lesion recurrence were further assessed at 24 months. RESULTS: Data from 97 patients (105 lesions) were included in the 3-month per-protocol analysis. Complete response rates did not differ significantly between groups (51/52 [98%] lesions with surgery vs 48/53 [91%] lesions with methyl aminolevulinate PDT; difference [95% confidence interval], 4.8% (-3.4% to 13.0%]; P =.25). At 12 months, tumor-free rates were 50 (96%) of 52 lesions with surgery vs 44 (83%) of 53 with methyl aminolevulinate PDT (P =.15). More patients treated with methyl aminolevulinate PDT than surgery had an excellent or good cosmetic outcome at all time points (significant at 12 and 24 months on patient assessment, P<.05, and at 3, 12, and 24 months on investigator evaluation, P<.001). At 24 months, 5 lesions that had initially cleared with methyl aminolevulinate PDT had recurred, compared with 1 after surgery. CONCLUSIONS: Methyl aminolevulinate PDT is an effective treatment for nodular BCC, and while there is a trend for higher recurrence with this modality, it conveys the advantage over surgery of better cosmesis.

Administration, Topical↗

Effects of oral vitamin E and beta-carotene supplementation on ultraviolet radiation-induced oxidative stress in human skin.

BACKGROUND: Ultraviolet radiation (UVR) generates reactive oxygen species in skin that can play a role in skin damage, but reports about the photoprotective properties of oral antioxidant supplements are conflicting. OBJECTIVE: We examined the ability of 2 lipid-soluble antioxidants, vitamin E and beta-carotene, to reduce markers of oxidative stress and erythema in human skin exposed to UVR. DESIGN: Sixteen healthy subjects took either alpha-tocopherol (n = 8; 400 IU/d) or beta-carotene (n = 8; 15 mg/d) for 8 wk. Biopsy samples before and after supplementation were taken from unexposed skin and skin 6 h after 120 mJ/cm(2) UVR. The effects of supplements on markers of oxidative stress in skin and the minimal erythema dose to UVR were assessed. RESULTS: Supplementary vitamin E was bioavailable, the plasma concentration increased from 14.0 +/- 0.66 (x +/- SEM) to 18.2 +/- 0.64 mug/mL (P < 0.01), and the skin concentration increased from 0.55 +/- 0.09 to 1.6 +/- 0.19 ng/mg protein (P < 0.01). Supplementary beta-carotene increased plasma concentrations from 1 +/- 0.3 to 2.25 +/- 0.3 mug/mL (P < 0.05), but skin concentrations were undetectable. Before vitamin E supplementation, UVR increased the skin malondialdehyde concentration from 0.42 +/- 0.07 to 1.24 +/- 0.16 nmol/mg protein (P < 0.01), whereas oxidized or total glutathione increased from 9.98 +/- 0.4% to 12.0 +/- 1.0% (P < 0.05). Vitamin E supplementation significantly decreased the skin malondialdehyde concentration, but neither vitamin E nor beta-carotene significantly influenced other measures of oxidation in basal or UVR-exposed skin. CONCLUSIONS: Vitamin E or beta-carotene supplementation had no effect on skin sensitivity to UVR. Although vitamin E supplements significantly reduced the skin malondialdehyde concentration, neither supplement affected other measures of UVR-induced oxidative stress in human skin, which suggested no photoprotection of supplementation.

Administration, Oral↗

Treatment of polymorphic light eruption.

Polymorphic light eruption (PLE) is a highly prevalent photosensitivity disorder, estimated to affect 11-21% people in temperate countries. Typically, PLE appears as a recurrent pruritic eruption comprising papules and/or vesicles and/or plaques, which occurs on photo-exposed skin sites following sun exposure, and which heals without scarring. Commoner in females, the aetiology is uncertain, although there is evidence of an immune basis. We perform a review of the prophylaxis and treatment of this condition. While sun protection, corticosteroids and desensitization phototherapy are the mainstays of management, a range of anti-inflammatory and immunomodulatory agents are reported.

Adrenal Cortex Hormones↗

Effect of eicosapentaenoic acid, an omega-3 polyunsaturated fatty acid, on UVR-related cancer risk in humans. An assessment of early genotoxic markers.

Dietary omega-3 polyunsaturated fatty acids (omega-3 PUFAs) protect against photocarcinogenesis in animals, but prospective human studies are scarce. The mechanism(s) underlying the photoprotection are uncertain, although omega-3 PUFAs may influence oxidative stress. We examined the effect of supplementation on a range of indicators of ultraviolet radiation (UVR)-induced DNA damage in humans, and assessed effect on basal and post-UVR oxidative status. In a double-blind randomized study, 42 healthy subjects took 4 g daily of purified omega-3 PUFA, eicosapentaenoic acid (EPA), or monounsaturated, oleic acid (OA), for 3 months. EPA was bioavailable; the skin content at 3 months showing an 8-fold rise from baseline, P < 0.01. No consistent pattern of alteration in basal and UVR-exposed skin content of the antioxidants glutathione, vitamins E and C or lipid peroxidation, was seen on supplementation. Sunburn sensitivity was reduced on EPA, the UVR-induced erythemal threshold rising from a mean of 36 (SD 10) mJ/cm(2) at baseline to 49 (16) mJ/cm(2) after supplementation, P < 0.01. Moreover, UVR-induced skin p53 expression, assessed immunohistochemically at 24 h post-UVR exposure, fell from a mean of 16 (SD 5) positive cells/100 epidermal cells at baseline to 8 (4) after EPA supplementation, P < 0.01. Peripheral blood lymphocytes (PBL) sampled on 3 successive days both pre- and post-supplementation, showed no change with respect to basal DNA single-strand breaks or oxidative base modification (8-oxo-dG). However, when susceptibility of PBL to ex vivo UVR was examined using the comet assay, this revealed a reduction in tail moment from 84.4 (SD 3.4) at baseline to 69.4 (3.1) after EPA, P = 0.03. No significant changes were seen in any of the above parameters following OA supplementation. Reduction in this range of early markers, i.e. sunburn, UVR-induced p53 in skin and strand breaks in PBL, indicate protection by dietary EPA against acute UVR-induced genotoxicity; longer-term supplementation might reduce skin cancer in humans.

Adult↗

Influence of eicosapentaenoic acid, an omega-3 fatty acid, on ultraviolet-B generation of prostaglandin-E2 and proinflammatory cytokines interleukin-1 beta, tumor necrosis factor-alpha, interleukin-6 and interleukin-8 in human skin in vivo.

Dietary omega-3 polyunsaturated fatty acids (omega-3 PUFA) reduce sunburn, an acute inflammatory response, in humans. We assessed whether this may be mediated by reduced ultraviolet-B (UV-B) induction of proinflammatory mediators tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta, IL-6, IL-8 and prostaglandin (PG)E(2) in healthy skin. In a double-blind, randomized study, 28 humans received 4 g daily of 95% ethyl esters of eicosapentaenoic acid (EPA) or oleic acid (OA) orally for 3 months. Skin biopsies and suction blister fluid were taken from unexposed and UV-B-exposed skin and examined for mediator expression immunohistochemically and quantitatively by immunoassay; plasma levels were also assayed. The subjects taking EPA, but not OA, showed a significant rise in their minimal erythemal dose (MED) (data reported elsewhere). Before supplementation, irradiation with 3x MED UV-B increased blister fluid TNF-alpha, IL-6, IL-8 and PGE(2) at 16 h (all P < 0.001). No significant change occurred in baseline or UV-B-induced skin levels of cytokines after either supplement, whereas UV-B induction of PGE(2) was abolished after EPA but not OA. Immunohistochemical expression of the cytokines at baseline and after UV-B was unaltered by EPA and OA; circulating cytokine and PGE(2) levels were also unchanged. Hence, in healthy skin in vivo, there was no evidence that reduction of the sunburn response by EPA is mediated by the proinflammatory cytokines examined; abrogation of UV-B-generated PGE(2) may play a role.

Adult↗