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Biomedical subjects

W J Cunliffe

Publications and source records attributed to W J Cunliffe.

At least 19 recordsLinked to original sources
PubMed1992

Comparative study of calcipotriol (MC 903) ointment and betamethasone 17-valerate ointment in patients with psoriasis vulgaris.

BACKGROUND: Topical vitamin D analogues have been reported to be an effective treatment in patients with psoriasis. Comparative studies with existing treatments are required. OBJECTIVE: Our purpose was to compare the effectiveness of calcipotriol (50 micrograms/gm) and betamethasone 17-valerate (1 mg/gm) ointments twice daily in the treatment of stable plaque psoriasis. METHODS: This study was a randomized, double-blind comparison over 6 weeks in 409 patients. Efficacy, as measured by the Psoriasis Area and Severity Index (PASI), and safety were assessed at 2, 4, and 6 weeks. RESULTS: Reduction of PASI was statistically significant at all time points for both treatments but there were no significant between-treatment differences. At the completion of 6 weeks of treatment, the mean PASI reduction was 5.50 for calcipotriol and 5.32 for betamethasone (95% confidence interval [CI] -0.40 to 0.78). Analysis of patient assessment at 6 weeks showed clearance or marked improvement in 61.2% of the calcipotriol patients and 50.5% with betamethasone (95% CI 1.4 to 20.8). Calcipotriol produced significantly more local side effects (19.5% compared with 3.9%, p less than 0.001); however, these were minimal leading to withdrawal in only 3 of 205 patients. CONCLUSION: Calcipotriol ointment was as effective as betamethasone 17-valerate ointment as measured by the PASI and superior as measured by self-assessment in patients with stable plaque psoriasis. Both treatments were well tolerated.

Betamethasone Valerate↗
PubMed1992

Guidelines for optimal use of isotretinoin in acne.

Isotretinoin is most effective for patients with acne who fail to respond to other forms of treatment; virtually all patients respond to isotretinoin, 0.5 to 1.0 mg/kg/day. As many as 61% of patients are cured after one course, but 39% require further isotretinoin (16%) or oral antibiotics (23%). The relapse rate can be reduced by the administration of the higher dose of 1 mg/kg/day (thus achieving a significant cumulative dose of > 120 mg/kg), especially to young patients and men with truncal acne and more severe disease. About 85% require a 4-month course, but 15% require longer treatment, with some up to 10 months. There are several reasons for a slow response to treatment, including the presence of macrocomedones, ovarian dysfunction, and as-yet unknown factors. Macrocomedones can be treated with light cautery, ovarian dysfunction with hormonal therapies, and in those persons who have no obvious explanation for slow response, persistence with isotretinoin alone is required. Repeat courses of isotretinoin can also be given. Six years ago most patients treated with isotretinoin had severe acne (60%), but today most patients (60%) have therapy-resistant moderate acne. Isotretinoin is a consideration in such patients to reduce the physical and psychological effects of acne, particularly because there is no simple method to treat acne scars.

Acne Vulgaris↗
PubMed1992

Pro-inflammatory levels of interleukin-1 alpha-like bioactivity are present in the majority of open comedones in acne vulgaris.

The factors that initiate the inflammatory response in acne are not known. The presence of pro-inflammatory cytokines in acne comedones was therefore investigated. One hundred eight open comedones were collected from 18 untreated acne patients (10 male, 8 female). Each comedone was homogenized and centrifuged, and the supernatant was analyzed for bioactive and immunochemically detectable IL-1 alpha, IL-1 beta, and TNF alpha. Viable counts of propionibacteria, staphylococci, and Malassezia spp. were determined in the comedone pellet. Bioactive IL-1 alpha-like material was demonstrated in 76% of open comedones (range of 23-4765 pg IL-1 alpha-like bioactivity/mg of comedone material). In 58% of comedones, levels exceeded 100 pg/mg. There was no correlation between IL-1 alpha-like bioactivity and IL-1 alpha determined immunochemically. Bioactive IL-1 beta was not detected in any comedones. Twenty-four percent contained low levels of immunochemical IL-1 beta (range 12-103 pg IL-1 beta/mg comedone material). Bioactive TNF alpha was detected in three comedones with a further five comedones containing immunochemical TNF alpha (range of 61-820 pg TNF alpha/mg comedone material). The majority of open comedones (97%) contained microorganisms. There was, however, no significant correlation (Spearman's rank) between levels of any cytokine, in particular IL-1 alpha-like bioactivity, and numbers of microorganisms. Thus, bioactive IL-1 alpha-like material in the majority of open comedones may be concerned in the initiation of inflammation in acne following spongiosis or rupture of the pilosebaceous follicle wall.

Acne Vulgaris↗
PubMed1992

Simple assays of retinoid activity as potential screens for compounds that may be useful in treatment of psoriasis.

Human epidermal cell cultures were used to study the effects of retinoids on keratinocyte differentiation. Keratin profiles were studied by quantitative gel electrophoresis of culture extracts, whereas the extent of envelope formation was assessed in an enzyme-linked immunosorbent assay (ELISA) using an antibody that specifically recognizes keratinocyte envelopes. Exposure of cultures to a variety of different retinoids produced both dose-dependent decreases in keratin 16 with consequent increases in the keratin 14: keratin 16 ratio, and a decrease in envelope formation. The order of activity in both assays was similar: arotinoid ethyl ester (Ro 13-6298) greater than or equal to arotinoid acid (Ro 13-7410) much greater than all trans retinoic acid (Ro 1-5488) greater than acitretin (Ro 10-1670) greater than or equal to etretinate (Ro 10-9359), the only difference being that acitretin was slightly more active than etretinate in the keratin assay whereas these retinoids were equi-active in the envelope assay. Analysis of the lesional keratins of psoriasis patients showed that etretinate caused a reduction in keratin 16 and an increase in the keratin 14:keratin 16 ratio, although the magnitude of these changes and their correlation with clinical improvement was variable. As the in vitro assays reported here are simple and quick, they allow rapid screening of compounds for retinoid-like activity.

3T3 Cells↗
PubMed1992

The effect of zinc and erythromycin on the growth of erythromycin-resistant and erythromycin-sensitive isolates of Propionibacterium acnes: an in-vitro study.

The effect of zinc and erythromycin on cultures inoculated with mixtures of different ratios of erythromycin sensitive (ES) and resistant (ER) Propionibacterium acnes cells was studied in vitro. Propionibacterium acnes ES outgrew P. acnes ER in the absence of erythromycin and zinc. At low levels of erythromycin ES outgrew ER, whilst the addition of 600 pg/ml zinc further reduced the growth of ER compared to ES. Growth of ER and ES were similar at levels of erythromycin near the minimum inhibitory concentration (MIC) of ES cells. Concentrations above the MIC for ES cells inhibited ES but not ER cells. At the higher concentrations of erythromycin, the addition of 96 ng/ml zinc delayed the growth of ER cells, whilst the addition of 300 micrograms/ml zinc prevented the growth of ER cells. The combination of erythromycin and zinc, at appropriate concentrations, inhibits both ES and ER.

Bacteriological Techniques↗
PubMed1992

A double-blind evaluation of topical isotretinoin 0.05%, benzoyl peroxide gel 5% and placebo in patients with acne.

A double-blind, randomized study comparing isotretinoin gel (Isotrex), its vehicle base, and benzoyl peroxide was performed on 77 patients with mild to moderate acne vulgaris. The effect of treatment was assessed by acne grade and lesion count. The vehicle base had no effect, but both active groups produced significant improvements. Benzoyl peroxide and isotretinoin significantly reduced non-inflamed lesions at 4 (P < 0.05), 8 (P < 0.01), 12 (P < 0.01) weeks. Benzoyl peroxide had a more rapid effect on inflamed lesions, their being significant reductions at 4, 8 and 12 weeks (P < 0.01), whereas with isotretinoin there was a significant improvement at 12 weeks (P < 0.01). In addition, compared to placebo, both active treatments significantly reduced inflamed and non-inflamed lesions. Acne grade had improved significantly in the benzoyl peroxide group by 4 weeks (P < 0.01) and in the isotretinoin group by 8 weeks (P < 0.05). No significant change in haematological or biochemical parameters occurred. An irritant dermatitis occurred equally with both treatments but was well tolerated by the patients. This data confirms the clinical benefit of benzoyl peroxide in acne. The initial effect of isotretinoin on non-inflamed lesions in this study suggests that the prime mode of action is on comedone formation or separation whereas benzoyl peroxide has an effect on both comedones and inflammation.

Acne Vulgaris↗
PubMed1992

Seborrhoea--an indicator for poor clinical response in acne patients treated with antibiotics.

The relationship between sebum excretion rate (SER) and clinical improvement was investigated in 255 acne patients treated for 6 months with either oral erythromycin (1 g/day), minocycline (100 mg/day), oxytetracycline (1 g/day) or cotrimoxazole (400 mg/day); topical therapy was 5% benzoyl peroxide. In all but the cotrimoxazole treated group, there was a significant correlation between a high SER and reduced clinical response. This was particularly evident in those patients with an SER of greater than 2.5 micrograms/cm2/min. These patients showed only 17% improvement compared with 100% improvement in those subjects with an SER of 1.0 micrograms/cm2/min or less. The presence of obvious seborrhoea in a patient who has failed to respond to an adequate 6-month course of antimicrobial therapy, should indicate the earlier rather than later use of isotretinoin for their acne.

Acne Vulgaris↗
PubMed1992

Acute Achilles tendonitis following oral isotretinoin therapy for acne vulgaris.

We report three cases of acute Achilles tendonitis following administration of isotretinoin for acne vulgaris. In this rarely documented side-effect, the symptoms were intimately related to the isotretinoin therapy. Modification of dose regimes permitted control of the tendonitis and an eventual successful response to isotretinoin therapy. Oral isotretinoin has been in use for more than 10 years and is known to cause a wide variety of predictable side-effects the most common of which are cutaneous and dose related. Musculoskeletal problems are also well known to occur and these include myalgia, arthralgia and less commonly arthritis and muscle damage, however, isolated Achilles tendonitis has been reported on a rare and sporadic basis. We wish to report a series of three patients who developed acute Achilles tendonitis during administration of isotretinoin for acne.

Achilles Tendon↗
PubMed1992

Hormonally exacerbated hereditary angioedema.

Hereditary angioedema is a rare disorder which is associated with an inherited deficiency of the inhibitor of the activated first component of complement. Genetic transmission occurs in an autosomal dominant manner. Affected patients are heterozygotes, and their deficiency is incomplete, many of them having up to 20% of the normal amount of the inhibitor. We describe two cases of C1 esterase inhibitor deficiency occurring in a mother and daughter in whom the symptoms appeared to be related to the menstrual cycle or the taking of the oral contraceptive pill. Although both features have been mentioned in the literature, to the best of our knowledge premenstrual exacerbations have not been documented previously. We examined the likely basis of hormonally exacerbated hereditary angioedema.

Adolescent↗