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Biomedical subjects

R S Dawe

Publications and source records attributed to R S Dawe.

At least 37 records · Page 2Linked to original sources

Allergic contact dermatitis in venous leg ulcer patients.

Our aim was to determine the frequency and nature of contact sensitivity in venous leg ulcer patients in Lanarkshire. We performed patch testing with the European standard series, antimicrobials and medicaments on 200 patients referred to our leg ulcer clinics. Positive patch tests were found in 136 (68%) patients. Multiple allergies occurred in 102 (51%). The most frequent allergen groups were fragrances (30.5%), antimicrobials (19.5%), topical excipients (19.5%), rubber accelerators (13.5%) and topical corticosteroids (8%). We also found a high prevalence of positive patch tests to Intrasite gel (9.5%) and Hioxyl cream (8.5%), medicaments which are commonly used to treat leg ulcers in our area. Contact sensitivity is common in venous leg ulcer patients and has important implications for patient management. The allergens involved vary depending on local nursing practice. We suggest that all venous leg ulcer patients be patch tested with a locally relevant patch test series.

Adult↗

Ultraviolet A1 phototherapy.

Long-wavelength ultraviolet A (340-400 nm; UVA1) therapy is currently available in only a few dermatology departments. Equipment capable of delivering this waveband has been available since 1981, but it is only over the past decade that increasing numbers of studies assessing the potential of this as a therapy have been published. High-dose UVA1, which requires expensive and space-occupying apparatus, is effective as a monotherapy for acute flares of atopic dermatitis, but it has not yet been formally assessed as an adjunct, rather than as an alternative to conventional therapies including potent and very potent topical corticosteroids. Low-dose (which can be administered using a standard phototherapy cubicle fitted with appropriate lamps) and medium-dose UVA1 may be less effective for this indication. Another condition for which UVA1 is effective, and is particularly promising because we have no reliably effective treatment already, is localized scleroderma. It also appears to be effective in systemic lupus erythematosus (although it is not yet clear when it is indicated, and its safety needs to be assessed in more patients) and in polymorphic light eruption (although there have been no studies suggesting that UVA1 will have any advantages over standard prophylactic phototherapies). Open studies and case series suggest that UVA1 may prove beneficial for various other diseases, including cutaneous T-cell lymphoma, lichen sclerosus, keloids, systemic sclerosis and hand dermatitis. In the centres where it is available, UVA1 has already proved a useful addition to the range of phototherapies previously available. However, much more research is needed to confirm its efficacy for many of its potential indications, and to determine when and how it should be used.

Controlled Clinical Trials as Topic↗

A randomized controlled trial of narrowband ultraviolet B vs bath-psoralen plus ultraviolet A photochemotherapy for psoriasis.

BACKGROUND: In 1991, consensus guidelines recommended psoralen plus ultraviolet A photochemotherapy (PUVA) for those requiring second-line therapy for psoriasis. Narrowband (TL-01) UVB has since become more widely available, replacing the less effective broadband sources. Objectives To compare the efficacy of TL-01 UVB phototherapy and trimethoxypsoralen (TMP) bath-PUVA for chronic plaque psoriasis. PARTICIPANTS AND METHODS: A randomized, observer-masked, intraindividually controlled, paired (half-body) study was done in the Photo(chemo)therapy Unit in Ninewells Hospital and Medical School, Dundee. The study comprised 28 patients (skin phototypes I-III) with chronic plaque psoriasis. Each patient's body halves (sagittal plane) were treated independently, one-half with TL-01 UVB, the other with bath-PUVA. Both treatments were administered according to standard, optimized regimens. Treatment was continued until clearance or minimal residual activity (MRA), or a maximum of 30 treatments. The main outcome measures were treatments and time to clearance/MRA, the proportion reaching clearance/MRA, change in psoriasis severity score (scaling, erythema and induration) and remission durations. RESULTS: Of 18 who completed the study, all reached clearance/MRA with TL-01, but three were still not clear after 30 PUVA exposures. TL-01 achieved clearance/MRA a median of 11 (6.5-25; P = 0.001) days more quickly than PUVA, but required a median of 24.5 compared with 19 exposures [95% confidence interval (CI) for difference 1.5-5.5; P = 0.01]. Ten patients were withdrawn (four because of inadequate response of PUVA-treated halves). Analysed on an intention-to-treat basis, 21 of 28 (75%) of all participants reached clearance/MRA with TL-01 compared with 15 of 28 (54%) with PUVA (95% CI for difference 4-37%; P = 0.03). Remission durations did not differ. CONCLUSIONS: When administered according to these regimens in a skin phototype I-III population, TL-01 UVB is more efficacious than TMP bath-PUVA in the treatment of chronic plaque psoriasis.

Adult↗

Environmental effects and skin disease.

The skin is the largest organ in the body and one of its main functions is to protect the body from noxious substances, whether they are ultraviolet radiation, toxic chemicals or prolonged/repeated exposure to water. It is the level of exposure that determines if damage to the organism will result. The harm that can occur to the skin with sufficient exposure will be considered. Contact dermatitis, halogen acne, chemical depigmentation, connective tissue diseases and skin cancer are the conditions that will be covered in this chapter, as environmental exposure is important in their aetiologies. Systemic absorption will not be dealt with. Most environmental exposure to harmful substances will occur at work, but exposure may occur at home or during normal day-to-day activities.

Acne Vulgaris↗

A randomized controlled trial (volunteer study) of sitafloxacin, enoxacin, levofloxacin and sparfloxacin phototoxicity.

BACKGROUND: Fluoroquinolone antibiotics (FQs) are associated with phototoxic skin reactions following exposure to sunlight. OBJECTIVES: We aimed to compare the phototoxic potential of sitafloxacin, a novel FQ with three others: sparfloxacin, enoxacin, levofloxacin and placebo in Caucasian volunteers. In a second study, two dosage regimens of sitafloxacin were compared with placebo in Oriental subjects. METHODS: Randomized, placebo-controlled, assessor-blinded clinical trial. In 40 healthy Caucasians, sitafloxacin 100 mg twice a day (n = 8), sparfloxacin 200 mg day-1 (n = 8), enoxacin 200 mg three times a day (n = 8), levofloxacin 100 mg three times a day (n = 8) and placebo (n = 8) were given in oral doses for 6 days. In the second study, sitafloxacin 50 mg and 100 mg, both twice daily, were compared with placebo in 17 healthy Oriental subjects. Using an established monochromator technique, baseline threshold erythema levels were established pre-drug and on-drug. The phototoxic index (PI) baseline, minimal erythema dose (MED) divided by on-drug MED for each medication at each wavelength was determined and related to sitafloxacin peak plasma levels. The duration of susceptibility to phototoxicity was assessed by repeat phototesting daily after stopping medication. RESULTS: In the Caucasian study, sitafloxacin 100 mg twice a day produced mild ultraviolet (UV) A-dependent phototoxicity (median PI = 1.45) at 365 +/- 30 nm (half-maximum bandwidth), maximal at 24 h with normalization by 24 h postdrug cessation. The sparfloxacin group experienced severe phototoxicity maximal at 24 h and, unusually for an FQ, extended in the visible region (430 +/- 30 nm), maximal at 400 +/- 30 nm (median PI = 12.35) with abnormal pigmentation at on-drug phototest sites lasting, although fading, for up to 1 year. Enoxacin showed UVA-dependent phototoxicity (335-365 +/- 30 nm) median PI 3.94 (at 365 +/- 30 nm) returning to normal 48 h after stopping the drug. Fading pigmentation at phototoxic sites also lasted up to 1 year. Phototoxicity was not detected in the levofloxacin or placebo groups. In the Oriental study, no clinically relevant phototoxicity was seen with either sitafloxacin or placebo groups. CONCLUSIONS: We conclude that 100 mg twice a day sitafloxacin in Caucasians is associated with a mild degree of cutaneous phototoxicity. Enoxacin 200 mg three times a day and sparfloxacin 200 mg day-1 are much more photoactive. Sparfloxacin phototoxicity is induced by UVA and visible wavelengths. Levofloxacin and placebo failed to show a phototoxic effect. In the Oriental study, sitafloxacin 50 mg twice a day and 100 mg twice a day failed to demonstrate a clinically significant phototoxic effect.

Adult↗

Taking treatment to the patient: development of a home TL-01 ultraviolet B phototherapy service.

BACKGROUND: While most patients requiring phototherapy can attend for hospital-based out-patient ultraviolet (UV) B therapy, a significant number cannot attend because of geographical, work, economic and other reasons. OBJECTIVES: To determine whether there was a need for home phototherapy in the Tayside area and, if so, to establish protocols and then to assess if such a service would be workable. METHODS: Patients referred from dermatology out-patient clinics in Tayside for narrow-band UVB (TL-01) phototherapy completed a pilot questionnaire that was followed by a two-phase project. In phase 1, patients with psoriasis were trained to use the home phototherapy equipment (HoPE) within the hospital department under nursing supervision while a teaching package and protocols were developed. In phase 2, home phototherapy was made available for patient use in the community, supported by a specialist home phototherapy nurse. Waldmann UV100 home therapy units were used, with accurate dosimetry. Detailed treatment records were kept and questionnaires were used to assess acceptability and costs of therapy. RESULTS: Fifty-two pilot questionnaires were completed. Forty-two per cent of respondents found hospital phototherapy inconvenient and 75% felt phototherapy at home would be helpful. In phase 1, seven of 10 patients trained to use the HoPE completed therapy with the HoPE unit alone, reaching minimal residual activity (MRA) or clearance in a median of 18 exposures (median dose 10.38 J cm-2). In phase 2, 32 courses of home phototherapy were given to 30 patients. Of 23 with psoriasis, 18 reached clearance or MRA in a median of 22.5 exposures (median dose 9.84 J cm-2). Although self-reported erythema rates appeared higher than expected, all post-treatment questionnaire respondents would choose home phototherapy over hospital therapy if required in the future. CONCLUSIONS: UVB (TL-01) home phototherapy is a useful practical development that has fulfilled a need in our catchment area. Where appropriate training and support teams are available it appears to be similar in effectiveness to hospital therapy, to be safe and to be cost-effective for patients.

Adult↗

A randomized, observer-blinded trial of twice vs. three times weekly narrowband ultraviolet B phototherapy for chronic plaque psoriasis.

BACKGROUND: The optimum treatment frequency for narrowband (TL-01) ultraviolet B (NB-UVB) in psoriasis is not yet known. We have previously found three times weekly to be preferable to five times weekly treatment in our population. OBJECTIVES: To compare twice weekly with three times weekly NB-UVB phototherapy in chronic plaque psoriasis. METHODS: In an observer-blinded, randomized comparison, patients with chronic plaque psoriasis referred from dermatology out-patient clinics in Tayside for NB-UVB phototherapy received either twice weekly (Monday and Friday) or three times weekly (Monday, Wednesday and Friday) whole-body NB-UVB phototherapy following our standard departmental treatment protocol. Treatment was continued to clearance or until the fourth treatment after minimal residual activity (MRA) was first documented. Number of days in treatment, number of treatments, total dose and time to relapse were recorded. RESULTS: In total, 113 patients were recruited, skin phototypes I-III: 58 in the twice weekly and 55 in the three times weekly group. Forty patients in the twice weekly group reached clearance/MRA, as did 44 in the three times weekly group. It took 1.5 (95% confidence interval 1.3-1.7) times longer to reach clearance/MRA with twice weekly therapy, a geometric mean of 88 vs. 58 days (P < 0.0001). Small differences in numbers of treatments and total dose to reach clearance tended to favour three times weekly therapy, but these were not significant. CONCLUSIONS: Three times weekly NB-UVB clears psoriasis significantly faster than twice weekly treatment, and therefore is preferable for most patients.

Adolescent↗

The effect of methoxsalen dose on ultraviolet-A-induced erythema.

There is considerable interindividual variation in bioavailability of Methoxsalen (8-methoxypsoralen) after ingestion of the standard dose used in photochemotherapy (psoralen plus ultraviolet A). A dose change may be used to alter the degree of photosensitivity, although there is limited information on the effect of 8-methoxypsoralen dose alterations on phototoxicity within individuals. We studied the effect of changes of 8-methoxypsoralen dose over a narrow range in 15 subjects with psoriasis. Two hours after ingestion, serum 8-methoxypsoralen concentration was determined and phototesting was performed at 350 +/- 30 nm (0.45-14 J per cm2). The minimal phototoxic dose at 72 h was recorded, erythema was measured using a reflectance instrument, and dose-response curves were constructed. Each subject was tested on three occasions using doses of 25 mg per m2 (conventional dose) or conventional dose +/- 10 mg. Median serum 8-methoxypsoralen concentration increased from 96 to 143 to 229 ng per ml with dose increases from conventional dose - 10 mg to conventional dose and conventional dose + 10 mg, respectively (p < 0.001). The median minimal phototoxic dose and D0.025 (the objective equivalent of the minimal phototoxic dose derived from the dose-response curve) were significantly reduced with increasing 8-methoxypsoralen dose from conventional dose minus 10 mg (minimal phototoxic dose 1.7 J per cm2; D(0.025) 2.8 J per cm2) to conventional dose (1.2; 1.4 J per cm2) and conventional dose plus 10 mg (0.9; 1.0 J per cm2) (p < 0.001). Change in 8-methoxypsoralen dose had no detectable effect on the maximum slope of the psoralen plus ultraviolet A erythema dose-response curve. Thus, 8-methoxypsoralen dose changes within individuals, over a narrow but clinically relevant range, significantly altered the threshold response to psoralen plus ultraviolet A erythema but not the rate of increase in erythema with increasing ultraviolet A dose.

Adult↗

The natural history of chronic actinic dermatitis.

OBJECTIVE: To determine the prognosis for resolution of abnormal cutaneous photosensitivity in patients with chronic actinic dermatitis (also known as the photosensitivity dermatitis and actinic reticuloid syndrome). DESIGN: Historical cohort study involving follow-up of patients for up to 24 years from diagnosis. SETTING: A Scottish tertiary referral center for investigation of photodermatosis. PATIENTS: One hundred seventy-eight patients with chronic actinic dermatitis, 62% of a cohort of 285 living patients identified in the Photobiology Unit database. INTERVENTIONS: Recall for repeated clinical assessment and monochromator phototesting. All patients underwent patch testing when initially assessed; this was repeated at follow-up in a subgroup of patients. MAIN OUTCOME MEASURES: Resolution of abnormal photosensitivity, defined as clinical resolution and return of phototest responses to within normal population limits. In addition, possible prognostic factors for resolution of photosensitivity were examined. RESULTS: The probability of abnormal photosensitivity resolving by 10 years from diagnosis is 1 in 5. Particularly severe abnormal UV-B photosensitivity (minimal erythema dose at 305+/-5 nm half-maximum bandwidth, < or =5.6 mJ x cm(-2)) and the identification of separate contact allergens in 2 or more patch test batteries are predictors of a poorer prognosis for resolution. Loss of contact allergies was not associated with a different prognosis for photosensitivity resolution. Our findings probably underestimate the probability of resolution, as those referred to a tertiary referral center and willing to attend for follow-up may include a disproportionate number of severely affected patients. CONCLUSIONS: Newly diagnosed patients can be told that most of them will improve with appropriate UV/visible light and allergen avoidance and that there is hope that their photosensitivity will completely resolve.

Adult↗

Narrowband TL-01 phototherapy for patch-stage mycosis fungoides.

BACKGROUND: Although patch-stage mycosis fungoides (MF) has a generally good prognosis, and long-term survival rates with current therapies (UV-B, photochemotherapy, topical nitrogen mustards, electron-beam therapy) are similar, there is concern regarding their potential adverse effects. Narrowband or TL-01 UV-B phototherapy (311 nm), in use for more than 10 years, is more effective than broadband UV-B for the treatment of psoriasis, with an efficacy approaching that of psoralen UV-A. This open study assesses TL-01 as an alternative therapy for patch-stage MF. OBSERVATIONS: Eight white patients (4 men, 4 women; age range, 66-83 years) with histologically proven patch-stage MF received TL-01 phototherapy 3 times weekly using a standard protocol. Complete clearance of MF was achieved in 6 cases in a mean of 9 weeks or 26 treatments (range, 20-37 weeks) and 4 patients have had prolonged remissions. Mean duration of clinical improvement has been 20 months (range, 11-40 months). Partial response to TL-01 or poor histologic improvement was associated with rapid relapse. CONCLUSIONS: TL-01 is an effective, convenient therapy that may have less risk of long-term adverse effects than current alternatives. Although larger prospective studies are necessary, for some patients intermittent courses of TL-01 may offer effective long-term therapy.

Aged↗

The effect of whole-body sunbed ultraviolet A exposure on the pharmacokinetics of the photolabile drug nifedipine.

The calcium antagonist nifedipine absorbs ultraviolet A (UVA) radiation and readily photodegrades in vitro to a toxic nitroso-pyridine photoproduct. We examined whether whole body exposure of normal subjects to sunbed UVA radiation would affect the pharmacokinetics of nifedipine. Eight healthy, male, Caucasian volunteers (phototypes I-III) participated in this ethically approved, randomised, cross-over study. Each subject attended on 2 occasions, one week apart, and on each occasion was given a single oral dose (10 mg) of nifedipine following which blood samples were collected at 0, 0.5, 1. 1.5, 2, 2.5, 3, 3.5, 4, 5, 6 and 7 h. During one of the visits, 15 min after nifedipine ingestion, a whole-body UVA (sunbed comprising Philips R-UVA lamps) dose of 70% of the individual's predetermined minimal phototoxic dose was delivered over a period of 17-36 min. Plasma nifedipine levels were measured using a standard reverse-phase high-performance liquid chromatography method. The area under the plasma concentration-time curve (AUC) of nifedipine during the UVA irradiation session (median 206 ng x ml(-1) x h(-1)) was significantly higher than during the non-irradiation control session (median 174.5 ng x ml(-1) x h(-1)) (P=0.03; 95% C.I. for difference in medians 9.9 to 55.9 ng x ml(-1) x h(-1)). UVA irradiation did not significantly affect any of the other measured pharmacokinetic parameters (Cmax, t 1/2, tmax). We demonstrate that sunbed UVA irradiation does not lead to in vivo photodegradation of nifedipine in healthy humans after a single dose. The apparent increase in AUC during UVA irradiation may be due to slightly slower metabolism of nifedipine in the presence of toxic photoproduct(s) or due to blood distribution changes affecting liver blood flow.

Adult↗

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↗

Pulse oximetry: a new tool to assess patients with leg ulcers.

The objective of the study was to investigate pulse oximetry as a guide to assessing patients with leg ulcers before treatment. Graduated elastic compression is the treatment of choice for uncomplicated venous leg ulcers, but is contra-indicated in patients with significant arterial disease. The standard assessment of arterial insufficiency by Doppler ultrasound ankle branchial pressure index (ABPI) has shortcomings which prompted this investigation of pulse oximetry as a possible additional, or alternative, method of assessment of patients with leg ulcers, prior to treatment with compression. The study, carried out on a population of patients attending hospital leg ulcer clinics, was designed to evaluate pulse oximetry assessment in the selection and monitoring of patients with venous leg ulceration leading to a prospective controlled study of ulcer healing in groups of patients with reduced and normal ABPI, selected for compression therapy by pulse oximetry criteria. Outcome measurement required follow-up of patients selected for compression therapy by pulse oximetry to record time to healing and rate of healing of leg ulcers. Results from the study show a fair correlation between the toe-finger oximetry index (TFOI) and Doppler ABPI. There is no difference between ulcer healing in patients with reduced and normal ABPI selected for treatment on the basis of pulse oximetry maximum compression pressure (MCP). In conclusion, pulse oximetry is an aid to the selection of patients who will benefit from compression therapy, but would be excluded on the basis of Doppler ABPI.

Humans↗