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  • 1
    Electronic Resource
    Electronic Resource
    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 (2001)
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 144 (2001), S. 0 
    Details
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2133.2001.04186.x
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  • 2
    Electronic Resource
    Electronic Resource
    Chronic actinic dermatitis in young atopic dermatitis sufferers (2000)
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 142 (2000), S. 0 
    Details
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2133.2000.03457.x
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  • 3
    Electronic Resource
    Electronic Resource
    Photopatch testing in photosensitive patients (2000)
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 142 (2000), S. 0 
    Details
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2133.2000.03401.x
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  • 4
    Electronic Resource
    Electronic Resource
    Guidelines for topical PUVA: a report of a workshop of the British Photodermatology Group (2000)
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 142 (2000), S. 0 
    Details
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2133.2000.03237.x
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  • 5
    Electronic Resource
    Electronic Resource
    Home phototherapy: report on a workshop of the British Photodermatology Group, December 1996 (1999)
    Oxford BSL : Blackwell Science Ltd
    British journal of dermatology 140 (1999), S. 0 
    Details
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2133.1999.02649.x
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  • 6
    Electronic Resource
    Electronic Resource
    Cholesterol supplementation objectively reduces photosensitivity in the Smith–Lemli–Opitz syndrome (2001)
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 144 (2001), S. 0 
    Details
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2133.2001.03964.x
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  • 7
    Electronic Resource
    Electronic Resource
    Fluorescence spectroscopy: a rapid, noninvasive method for measurement of skin surface thickness of topical agents (1997)
    Oxford, UK : Blackwell Publishing Ltd
    British journal of dermatology 136 (1997), S. 0 
    Details
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: We report the quantification of skin surface thickness of topical agents by in vivo fluorescence spectroscopy, and demonstrate its potential uses for assessment of application technique and substantivity.A series of studies were performed on forearm skin of eight normal subjects using three creams which have intrinsic fluorescence: a sunscreen (Neutrogena SPF15 waterproof cream), an antiseptic (Hewlett's cream) and a steroid (Trimovate (clobetasone butyrate) cream). Initially, the dose-response relationship was established for each agent by applying a series of five doses (0.5-8μ/cm2) and measuring cream fluorescence using appropriate excitation and emission wavelengths. Next, the influence of application technique was examined by comparing light application of cream with firm rubbing. Substantivity of the three ceams was assessed on dry skin by taking fluorescence measurements over 8 h. Finally, water resistance of 2 μ/cm2 of sunscreen and antiseptic cream were compared by measuring fluorescence after each of four water immersions. The fluorescence intensity was strongly correlated with the logarithm of surface density, r = 1.0, 0.92 and 0.98 for sunscreen, antiseptic and steroid creams, respectively, allowing derivation of a simple expression for equivalent thickness. Surface thickness of each cream was lower following firm rubbing compared with light application (P〈0.01). The rate constants for reduction of surface density of the three creams with time on dry skin were not significantly different. However, on washed skin, the rate constant was higher rate for Hewlett's than Neutrogena cream (0.503 and 0.243 h. respectively. P= 0.02), with a higher rate for each cream on wet compared with dry skin (P 〈0.001).Hence, fluorescence spectroscopy is a simple, rapid method for measurement of cream thickness in vivo. The many potential applications in dermatology include quantitative assessment of application technique and substantivity of topical agents.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1046/j.1365-2133.1997.d01-1135.x
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  • 8
    Electronic Resource
    Electronic Resource
    Cimetidine improves the therapeutic/toxic ratio of dapsone in patients on chronic dapsone therapy (1995)
    Oxford, UK : Blackwell Publishing Ltd
    British journal of dermatology 132 (1995), S. 0 
    Details
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: We have previously shown that cimetidine, given concurrently for 2 weeks to patients on chronic dapsone therapy, reduced methaemoglobinaemia by inhibiting the formation of the toxic hydro-xylamine metabolite of dapsone. The aim of the present study was to examine the effect of this combination on the benefit/toxic ratio of dapsone over a longer period.Eight patients (six dermatitis herpetiformis, one linear IgA disease, one folliculitis decalvans) on long-term dapsone 50-100 mg daily, took cimetidine 1·6g daily concurrently for 3 months. At 3-weekly intervals, a clinical assessment was made, plasma dapsone and methaemoglobin were measured, and parameters of oxidative haemolysis were monitored. The dapsone level rose from 2298±849 ng/ml (mean+SD) at baseline to 3006±1131 ng/ml at week 3 of cimetidine (P〈0·01). This rise in plasma dapsone was sustained during cimetidine administration, falling to 2446±954 ng/ml when cimetidine was stopped (P〈0·02). The methaemoglobin fell from 5·5·2·2% (mean±SD) at baseline to 3·9±1·1% at week 3 (P〈0·01). and remained low until week 12, when there was a return to baseline values (P〈0·01). The haemoglobin did not change from the baseline of 12·7·0·3 g/dl (mean±SD), and other parameters of haemolysis were unaltered. There was a fall in the visual analogue score for headache (P〈0·05), but this was not associated with any deterioration in control of the skin disorders.Hence, long-term concurrent cimetidine results in increased plasma dapsone levels without increased haemolysis, and is accompanied by reduced methaemoglobinaemia for more than 2 months. Cimetidine thus improves the therapeutic/toxic ratio of dapsone. Such a therapeutic strategy may be appropriate for patients who require high-dose dapsone, or those who are particularly susceptible to dapsone-induced haemotoxicity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2133.1995.tb05022.x
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  • 9
    Electronic Resource
    Electronic Resource
    PUVA and methotrexate therapy of psoriasis: how closely do dermatology departments follow treatment guidelines? (1994)
    Oxford, UK : Blackwell Publishing Ltd
    British journal of dermatology 131 (1994), S. 0 
    Details
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Following publication of treatment guidelines for patients with psoriasis, a six-centre audit was undertaken to assess current therapeutic practice for two second-line treatments, PUVA and methotrexate. The audit consisted of random sampling of casenotes by external auditors from a paired dermatology department, and assessment by questionnaire. One hundred and eight PUVA and 118 methotrexate casenotes were audited. The commonest indications for treatment were: (a) failure of topical therapy-PUVA (mean 81% of casenotes), methotrexate (84%); (b) repeated hospital admissions-PUVA (16%), methotrexate (25%).For both PUVA and methotrexate, some aspects of treatment were well documented: PUVA-psoralen dosage (91%), response to PUVA (89%), cumulative lifetime UVA dosage (81%); methotrexate-pretreatment assessment of full blood count (91%), urea and electrolytes (85%), liver function tests (84%). For other aspects documentation was less complete: PUVA-no documentation of presence/absence of skin cancer history (66%), note of photoactive drugs (32%); methotrexate—concurrent medication (69%), history of presence/absence of liver disease (36%). Another aspect which was poorly documented in both PUVA and methotrexate notes was whether advice on contraception/fertility had been given. There was no indication in 29 of 32 casenotes of females of child-bearing age receiving PUVA, and 52 of 63 case notes of relevant patients on methotrexate.This project has demonstrated that formal, multicentre audit based on published guidelines is a practical proposition.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2133.1994.tb08495.x
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  • 10
    Electronic Resource
    Electronic Resource
    Photosensitive Smith–Lemli–Opitz syndrome is not caused by a single gene mutation: analysis of the gene encoding 7-dehydrocholesterol reductase in five U.K. families (2005)
    Oxford, UK : Blackwell Science Ltd
    British journal of dermatology 153 (2005), S. 0 
    Details
    ISSN: 1365-2133
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background  Smith–Lemli–Opitz syndrome (SLOS) is an autosomal recessive malformation syndrome characterized by a disorder in cholesterol metabolism. SLOS is caused by mutations in the DHCR7 gene which encodes 7-dehydrocholesterol reductase, an enzyme that catalyses the final step in cholesterol biosynthesis. We have previously established the clinical and photobiological features of the photosensitivity that is frequently a feature of SLOS.Objectives  In this study, we have performed mutational analysis of the DHCR7 gene in individuals from five families with SLOS. In each family, one member was affected by severe photosensitivity as a manifestation of SLOS.Methods  Fifteen samples (including family controls) were screened using polymerase chain reaction amplification and direct automated sequencing.Results  Six different DHCR7 mutations were identified of which five were single point mutations that caused missense amino acid substitutions (P51H, T93M, L99P, E448K and R450L). The other was a splice site mutation (G→C in splice acceptor site) affecting the intron 8–exon 9 splice junction (IVS8-1 G→C). This splice site mutation and four of the five missense mutations have been previously published as causal in SLOS but the P51H is a novel mutation which has not previously been reported.Conclusions  This is the first study in which DHCR7 gene mutational analysis has been performed on SLOS subjects with severe photosensitivity and indicates that no single mutation is responsible for the photosensitivity which characterizes this disorder.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2133.2005.06761.x
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