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L E Rhodes

Publications and source records attributed to L E Rhodes.

At least 37 records · Page 2Linked to original sources
PubMed2001

Cholesterol supplementation objectively reduces photosensitivity in the Smith-Lemli-Opitz syndrome.

Smith-Lemli-Opitz (SLO) affected children have multiple congenital physical and mental abnormalities; photosensitivity to ultraviolet A (UVA) has recently become a recognized feature. We present a patient with SLO and prominent photosensitivity in whom detailed phototesting has been performed at baseline and following 6 months of cholesterol supplementation. There was significant improvement in the symptoms of photosensitivity, confirmed objectively by phototesting and accompanied by partial correction of the biochemical abnormalities seen in SLO. This case report is the first to show that cholesterol supplementation in SLO can lead to an objective improvement in the associated photosensitivity.

Adult↗
PubMed2001

A quantitative assessment of protoporphyrin IX metabolism and phototoxicity in human skin following dose-controlled delivery of the prodrugs 5-aminolaevulinic acid and 5-aminolaevulinic acid-n-pentylester.

BACKGROUND: Topical 5-aminolaevulinic acid (ALA) is widely used in photodynamic therapy (PDT) to generate protoporphyrin IX (PpIX) in the skin. However, other prodrugs may be more effective. OBJECTIVES: The pharmacokinetics of ALA- and ALA-n-pentylester-induced PpIX, together with the phototoxicity after PDT, were compared in human skin in vivo, using iontophoresis as a quantitative drug delivery system. METHODS: A series of six increasing doses of equimolar prodrug solutions was iontophoresed into normal skin of the upper inner arms of 20 healthy subjects. The kinetics of PpIX metabolism in skin (n = 4) and the response to light exposure, performed at 4.5 h (n = 6) and 6 h (n = 10) after application, were assessed by skin surface PpIX fluorescence and postirradiation erythema. RESULTS: ALA and ALA-n-pentylester showed a linear correlation between logarithm of dose and PpIX fluorescence (P < 0.005), and logarithm of dose and skin phototoxicity with irradiation at 4.5 h (P < 0.001 and P < 0.005, respectively) and 6 h (P < 0.05 and P < 0.0001, respectively) after iontophoresis. Higher phototoxicity was observed with ALA-n-pentylester than with ALA when sites were irradiated at 6 h, as indicated by the significantly lower theoretical threshold dose for erythema (P < 0.05) and the shift of the PpIX fluorescence/phototoxicity curve towards greater skin erythema at equal PpIX fluorescence levels. Depth of PpIX fluorescence in skin, as determined by fluorescence microscopy, was similar for both prodrugs, but a more homogeneous distribution of PpIX was seen with the more lipophilic ALA-n-pentylester. CONCLUSIONS: The observed greater phototoxicity of ALA-n-pentylester relative to ALA may be attributable to a more favourable PpIX localization in tissue and/or greater intrinsic toxicity.

Adult↗
PubMed2000

Hyperthermia to normal human skin in vivo upregulates heat shock proteins 27, 60, 72i and 90.

This study was performed to test the hypothesis that expression of heat shock proteins (HSPs) exhibits a spatially selective response within intact human skin following in vivo exposure to thermal stress. This response is believed to protect cells and tissues from further damage. Using Western blotting and immunohistochemistry, we studied the expression of a range of HSPs in normal human skin of 5 subjects prior to and following heating in vivo. The skin was heated to 41 +/- 0.5 degrees C for 1 h and biopsies were taken at 4, 8 and 24 h and from control, untreated skin. HSPs 27, 60, 72i, 90, 110 and heat shock constitutive (HSC)70 were expressed in normal skin, but the extent and distribution of these HSPs showed considerable variation. HSP27, 60 and 72i were found predominantly in the epidermis, whereas HSC70 showed weak epidermal staining but strong dermal expression. Heating the skin in vivo resulted in an increased skin content of HSP27, 60, 72i and 90, with maximal increase at 24 h following hyperthermia, while the skin content of HSC70 and HSP110 were unchanged. Significant increases in the content of HSP72i and HSP90 had occurred by 4 h following hyperthermia, with a mean +/-SEM of 206 +/- 50% and 197 +/- 38% of the control, untreated values, respectively (p<0.05). These findings indicate the complexity of HSP dynamics in human skin, and suggest that heating within the experimental range may protect the skin from further stresses for at least 24 h.

Adult↗
PubMed2000

Reduction in 8-methoxypsoralen immersion time alters the erythemal response to bath PUVA.

Topical psoralen plus ultraviolet A (PUVA) using 8-methoxypsoralen (8-MOP) bath solution is a well established and effective treatment in dermatology. The standard immersion time in the UK is 15 min, but a shorter bathing period could potentially increase treatment convenience. In order to examine the effect of reduction in immersion time on skin phototoxicity, we compared the erythemal response to UVA following 5 min and 15 min psoralen baths. The study was performed on the forearm skin of 7 healthy volunteers using an 8-MOP psoralen concentration of 2.6 mg/l. One forearm of each volunteer was soaked for 15 min and the other for 5 min, followed by immediate irradiation with a series of 10 doses of broadband UVA ranging from 0.1 J/cm2 to 6.9 J/cm2. At 72 h, the minimal phototoxic doses (MPDs) were noted and erythema readings (erythema index) were taken in triplicate with a reflectance instrument. The median MPD following 5 min immersion was 1.7 (range 0.7-2.7) J/cm2 compared with 1.0 (range 0.4-1.7) J/cm2 after 15 min treatment, with no significant difference. However, the mean slope of erythema dose-response on the 15-min treated side was significantly steeper than on the 5-min treated side, 0.036 and 0.021 respectively, P < 0.05. Hence, this preliminary work shows that reducing 8-MOP immersion time to 5 min reduces the erythemal response to UVA. It will clearly be necessary to examine the effect of a shortened immersion period on disease clearance before considering such a change to the topical PUVA regime.

Adult↗
PubMed2000

Sunscreen application technique in photosensitive patients: a quantitative assessment of the effect of education.

Photosensitive patients are known to apply insufficient sunscreen and to neglect several prominently exposed skin sites. The aim of this study was to use fluorescence spectroscopy to assess the effect of education on sunscreen application technique in the short and longer term. Six patients with longstanding photosensitivity conditions were asked to apply an intrinsically fluorescent sunscreen to exposed skin, as they normally would on a sunny day. Detailed fluorescence measurements were taken from 70 sites on the head, neck and arms. Using the previously established dose-response relationship for cream fluorescence, measurements were converted to equivalent thicknesses of cream. Patients were told the results of their sunscreen application assessment and deficiencies in technique were highlighted. Following education, application technique was reassessed twice, after intervals of 2 weeks and 6 months. Before education, sunscreen application was poor with inadequate amounts applied, and prominently exposed sites including ears, temples and neck often missed. At 2 weeks following education, improved application was seen at all sites, and the improvement was sustained at 6 months. Overall, education improved sunscreen application from a baseline median sunscreen thickness of 0.11 mg/cm2 to 0.82 mg/cm2 at 2 weeks and 1.13 mg/cm2 at 6 months (P<0.0001). Notably, median sunscreen thickness on the face improved from a baseline of 0.33 mg/cm2 to 1.51 mg/cm2 at 6 months. These findings demonstrate the importance of careful instruction to patients concerning sunscreen application technique; failure to do this may result in overconfidence in the ability of a sunscreen to protect. The next step is to assess a larger number of photosensitive patients with different diagnoses and to see whether improved technique correlates with improvement in clinical features.

Administration, Cutaneous↗
PubMed2000

Guidelines for topical PUVA: a report of a workshop of the British photodermatology group.

Psoralen photochemotherapy [psoralen ultraviolet A (PUVA)] plays an important part in dermatological therapeutics, being an effective and generally safe treatment for psoriasis and other dermatoses. In order to maintain optimal efficacy and safety, guidelines concerning best practice should be available to operators and supervisors. The British Photodermatology Group (BPG) have previously published recommendations on PUVA, including UVA dosimetry and calibration, patient pretreatment assessment, indications and contraindications, and the management of adverse reactions.1 While most current knowledge relates to oral PUVA, the use of topical PUVA regimens is also popular and presents a number of questions peculiar to this modality, including the choice of psoralen, formulation, method of application, optimal timing of treatment, UVA regimens and relative benefits or risks as compared with oral PUVA. Bath PUVA, i.e. generalized immersion, is the most frequently used modality of topical treatment, practised by about 100 centres in the U.K., while other topical preparations tend to be used for localized diseases such as those affecting the hands and feet. This paper is the product of a recent workshop of the BPG and includes guidelines for bath, local immersion and other topical PUVA. These recommendations are based, where possible, on the results of controlled studies, or otherwise on the consensus view on current practice.

Administration, Oral↗
PubMed2000

Photodynamic therapy.

Explore the source record for details and available documents.

Hematoporphyrin Derivative↗
PubMed2000

Comparison of the pharmacokinetics and phototoxicity of protoporphyrin IX metabolized from 5-aminolevulinic acid and two derivatives in human skin in vivo.

Our novel approach was to compare the pharmacokinetics of 5-aminolevulinic acid (ALA), ALA-n-butyl and ALA-n-hexylester induced protoporphyrin IX (PpIX), together with the phototoxicity after photodynamic therapy (PDT) in human skin in vivo, using iontophoresis as a dose-control system. A series of four increasing doses of each compound was iontophoresed into healthy skin of 10 volunteers. The kinetics of PpIX metabolism (n = 4) and the response to PDT (n = 6) performed 5 h after iontophoresis, were assessed by surface PpIX fluorescence and post-irradiation erythema. Whilst ALA-induced PpIX peaked at 7.5 h, highest PpIX fluorescence induced by ALA-n-hexylester was observed at 3-6 h and no clear peak was seen with ALA-n-butylester. With ALA-n-hexylester, more PpIX was formed after 3 (P < 0.05) and 4.5 h, than with ALA or ALA-n-butylester. All compounds showed a linear correlation between logarithm of dose and PpIX fluorescence/phototoxicity at 5 h, with R-values ranging from 0.87 to 1. In addition, the ALA-n-hexylester showed the tendency to cause greater erythema than ALA and ALA-n-butylester. Fluorescence microscopy (n = 2) showed similar PpIX distributions and penetration depths for the three drugs, although both ALA esters led to a more homogeneous PpIX localization. Hence, ALA-n-hexylester appears to have slightly more favorable characteristics for PDT than ALA or ALA-n-butylester.

Adult↗
PubMed1999

Sunscreen application by photosensitive patients is inadequate for protection.

Photosensitive patients often comment that sunscreen products seem of little benefit. We used fluorescence spectroscopy to assess quantitatively their sunscreen application technique. A dose-response relationship for sunscreen skin surface thickness and fluorescence intensity was determined for an intrinsically fluorescent sunscreen, Neutrogena sun protection factor (SPF) 15. Ten women with long-standing photosensitivity conditions were asked to apply this sunscreen in the manner they would normally on a bright sunny day. Fluorescence measurements were taken from all unclothed body areas, comprising 17 sites of the head, neck, upper and lower limbs. Geometric regression analysis of the dose-response data showed a high level of correlation (r = 0.99) between sunscreen thickness and fluorescence intensity, allowing fluorescence measurements to be converted to an equivalent sunscreen thickness. The overall median sunscreen thickness was 0.5 mg/cm2, with median thicknesses of individual sites ranging from 0 to 1.2 mg/cm2. The most frequently missed sites were the posterior neck, lateral neck, temples and ears, all of which had median thicknesses of 0 mg/cm2. Hence, photosensitive patients fail to apply sunscreen in some prominently exposed sites, and use average thicknesses far less than the manufacturers' recommendation (2 mg/cm2). The level of protection is much lower than anticipated from the stated SPF of the product.

Adult↗
PubMed1999

Characterization of photosensitivity in the Smith-Lemli-Opitz syndrome: a new congenital photosensitivity syndrome.

Photosensitivity has recently been reported as a feature of the Smith-Lemli-Opitz syndrome (SLO). The aim of this study was to establish the photobiological features of this disorder and to examine the hypothesis that the photosensitivity is caused by the high levels of 7-dehydrocholesterol found in SLO. All known cases of SLO in the U.K. were reviewed and clinical details of photosensitivity were recorded in detail. The action spectrum of the photosensitive eruption was defined by monochromator light testing. Thirteen of the 23 subjects (57%) had severe photosensitivity, and in 10 there was no photosensitivity. No correlation was identified between levels of 7-dehydrocholesterol and severity of photosensitivity, suggesting that the photosensitivity in SLO is not caused by a direct phototoxic effect mediated by 7-dehydrocholesterol. A novel pattern of photosensitivity was observed, with onset of a sunburn-like erythema on sun-exposed skin within minutes of sun exposure, which persisted in most cases for up to 24-48 h before fading. Monochromator light testing in three subjects showed an ultraviolet (UV) A-mediated photosensitivity eruption with greatest photosensitivity at 350 nm. Photosensitivity is a common and prominent feature of SLO and appears to be UVA-mediated. Elucidation of its biochemical basis may provide insight into normal cutaneous protective mechanisms against UVA-induced photodamage, and also sun sensitivity in general.

Adolescent↗
PubMed1999

Blister fluid cytokines in cutaneous inflammatory bullous disorders.

Cytokines are important regulators of immune and inflammatory reactions in the skin, and may contribute to inflammatory blister induction. We examined the profiles of interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) in fluid of spontaneous blisters in the immune-based inflammatory disorders bullous pemphigoid (8 patients), allergic contact dermatitis (5 patients) and toxic epidermal necrolysis (5 patients). These were compared with levels in 9 patients with burns, i.e. inflammatory blisters of non-immune aetiology, and 4 patients with blisters of physical origin. Very high levels of IL-6 were found in bullous pemphigoid and toxic epidermal necrolysis (p<0.001) compared with non-inflammatory and burn blisters. TNF-alpha levels were high in bullous pemphigoid and burns, but undetectable in non-inflammatory blisters. The pattern in bullous pemphigoid (very high IL-6, high TNF-alpha) differed substantially from toxic epidermal necrolysis (very high IL-6, low TNF-alpha), while burns and allergic contact dermatitis showed lesser elevation of both cytokines. Hence, differences in cytokine profiles were identified, although the relevance to underlying pathomechanisms is uncertain.

Blister↗
PubMed1999

Home phototherapy: report on a workshop of the British Photodermatology Group, December 1996.

Phototherapy is a popular and effective treatment for many patients with skin diseases. However, repeated journeys to hospital for phototherapy can be inconvenient and expensive. If it were available, many patients might prefer home-based phototherapy as long as it was safe and effective. Indeed, many psoriasis patients already self-treat with ultraviolet A sunbeds at home. This report represents a consensus view from a British Photodermatology Group workshop held in December 1996, the purpose of which was to examine the potential role of home-based phototherapy in dermatological practice. We conclude that home-based therapy represents a suboptimal treatment with greater attendant risks than phototherapy in a hospital environment. The level of medical supervision of the home treatment is crucial to its safety and effectiveness. Until further studies are forthcoming, home phototherapy should be largely restricted to those with overwhelming difficulties in attending hospital.

Home Care Services↗
PubMed1998

Dietary fish oil as a photoprotective agent in hydroa vacciniforme.

Hydroa vacciniforme is a troublesome and scarring photosensitivity disorder for which treatment is unsatisfactory. Dietary fish oil rich in omega-3 polyunsaturated fatty acids reportedly increases the resistance to ultraviolet-induced erythema and rash provocation in polymorphic light eruption. We report for the first time the response of hydroa vacciniforme to dietary fish oil. Three Caucasian boys with the condition were placed on MaxEPA, five capsules daily. Phototesting was performed at baseline and after 3 months supplementation. At baseline, low erythemal thresholds were seen to monochromated UVA at 350 and 370 nm in all three boys, while one also had a low threshold to 320 nm (UVA) and another showed a low threshold to 300 nm (UVB). Broad-band UVA provocation challenge produced typical skin lesions in all the subjects. Following fish oil, all the boys showed reduced erythemal sensitivity to UVA and one also showed reduced sensitivity to UVB. Provocation challenge revealed a reduced response in all three children. Clinically, these changes were accompanied by pronounced improvement in one child, mild improvement in the second child, but no improvement in the third. The third boy subsequently showed good clinical response to azathioprine.

Child↗
PubMed1998

Hepatic cytochrome P450 CYP2C activity in psoriasis: studies using proguanil as a probe compound.

Retinol and proguanil are metabolised by the same family of hepatic cytochrome P450, i.e. CYP2C. We used proguanil as a probe to study CYP2C activity, and by implication retinol metabolism, in psoriasis. In vitro studies showed that retinol competitively inhibited the hepatic metabolism of proguanil to cycloguanil. Proguanil metabolism was assessed in 82 patients with chronic plaque psoriasis. Following proguanil orally (200 mg), urine was analysed for proguanil and cycloguanil. A proguanil to cycloguanil ratio < 1 signified extensive metabolism and a ratio > 10 poor metabolism. A wider range of ratios was observed in psoriasis than previously reported for normal subjects. The proguanil to cycloguanil ratio was assessed in 10 cases each of know severe and mild psoriasis. Low CYP2C activity was associated with severe psoriasis, poor metaboliser status occurring in 50% of the severe group, but in none of the mild cases, p < 0.01. These findings may indicate differences in retinoid metabolism in psoriasis.

Administration, Oral↗