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Biomedical subjects

R S Barnetson

Publications and source records attributed to R S Barnetson.

At least 37 records · Page 2Linked to original sources

Regression in skin tumours: a common phenomenon.

Regression in epithelial skin tumours is a common phenomenon, and this may be partial or complete. In keratoacanthoma and familial self-healing epithelioma, nearly all the tumours regress completely. The incidence of total regression in melanoma and basal cell carcinoma is unknown, but in 25% of melanomas and 50% of basal cell carcinomas there is evidence of partial regression on histological examination. Previous studies carried out in our laboratories have indicated that regression of skin tumours is likely to be mediated by activated CD4+ T lymphocytes, possibly via cytokine secretion.

CD4-Positive T-Lymphocytes↗

Non-infective mucocutaneous presentations of human immunodeficiency virus infection.

Infection with human immunodeficiency virus (HIV) commonly manifests as one of many skin signs. Early diagnosis is essential. The present review discusses the likely non-infective presentations of HIV infection from the perspective of the dermatologist. While most diseases discussed also occur outside the setting of HIV infection, those clinical and pathological features which are distinctive will be highlighted.

Acute Disease↗

Prediction of minimal erythema dose with a reflectance melanin meter.

The relationship between skin pigmentation and sensitivity to ultraviolet (UV) radiation-induced erythema was investigated in 60 healthy subjects of sun-reactive skin types I-V. Using a portable reflectance spectrometer, skin pigmentation was measured as the 'melanin index' (MI) in all subjects. A solar-simulated array of filtered UVA and UVB-emitting fluorescent lamps was then used to determine the UVB minimal erythema dose (MED) of each subject. MI readings and MED testing were both performed on the subjects' mid to upper backs. Using this technique, we found a close correlation between MI and MED. Comparison of the mean MI or MED of subjects with different skin types revealed progressive differences in MI and MED between all five skin types. Erythema dose-response curves, which provide further information about UV sensitivity, were also calculated for 43 subjects. A significant negative correlation was found between the gradients of these curves and both MI and MED, indicating that paler subjects respond more strongly to increments of UV above the MED than subjects with greater pigmentation. Our results indicate that although traditional, subjective means of predicting UV sensitivity to erythema are not without some value, MED correlates particularly strongly with objective measures of skin pigmentation. We therefore conclude that the reflectance spectrometer can rapidly and accurately predict UVB sensitivity, and should prove clinically useful for planning and optimizing UVB phototherapy.

Adult↗

Chrysiasis after low-dose gold and UV light exposure.

We describe a case of chrysiasis in a 54-year-old woman. The diagnosis was confirmed by light microscopy, transmission electron microscopy, and radiographic microanalysis. The condition developed after a relatively low dose of gold. We propose that chrysiasis developed because of the patient's exposure to the intense UV light in Australia.

Antirheumatic Agents↗

Sweet's syndrome associated with Behçet's disease.

A case of acute febrile neutrophilic dermatosis (Sweet's syndrome) associated with Behçet's disease occurring in a 48 year old woman is reported. She fulfilled the diagnostic criteria for both Sweet's syndrome and Behçet's disease. There have been several reports of this association. Herpes simplex virus was isolated from a genital ulcer in our patient. The possible role of herpes simplex virus in this interesting association of Behçet's disease and Sweet's syndrome is discussed and a review of the literature is made.

Behcet Syndrome↗

Beta-1,3-D-glucan gel in the treatment of solar keratoses.

beta-1,3-D-glucans are yeast-derived carbohydrate polymers which have been shown to be potent immunoresponse modulators which promote the regression of certain tumours. To date there is no published data concerning the efficacy of topical beta-1,3-D-glucan in the treatment of solar keratoses. This randomized double-blind prospective pilot study of 20 patients was performed to investigate the efficacy and skin tolerance of beta-1,3-D-glucan gel versus placebo in the treatment of solar keratoses. The results of this study showed no significant benefit in using beta-1,3-D-glucan gel over placebo in reducing counts of solar keratoses. No adverse effects were reported by any patient at any stage of the trial.

Administration, Cutaneous↗

Modulation of Ia+ Langerhans cell numbers in vivo by cultured epidermis derived supernatants and by GM-CSF.

This paper demonstrates that epidermal cells in culture produce an activity which can increase the frequency of Ia+ epidermal Langerhans cells (LC). This was achieved by treating mice topically with a mixture containing supernatant derived from primary culture of murine epidermis (ES) and a synthetic corticosteroid, triamcinolone acetonide (TAC). The presence of the supernatant in the mixture partially protected the Ia+ LC from depletion by the steroid. The Ia+ LC frequency increasing activity was measured as the difference between the Ia+ LC frequency due to treatment with steroid mixed with supernatant and the Ia+ LC frequency due to treatment with steroid mixed with negative control medium. The mean frequency of Ia+ LC in epidermis treated with TAC mixed with ES was 606(SD 43) cells/mm2, as compared with 486 (SD 68) cells/mm2 in the epidermis treated with TAC mixed with control medium. The activity appeared to be caused by (a) proteinaceous factor(s). A fraction of ES which was retained above a > or = 10 KDa molecular weight cut-off membrane was capable of partially protecting Ia+ LC frequency from TAC depletion. Supernatants from cultured lymph nodes, dermis as well as the squamous cell carcinoma lines T7 and T79, but not the human osteosarcoma cell-line 143B, also contained similar activities. We demonstrate that GM-CSF also increased the number of Ia+ epidermal LC when applied topically to mouse skin in this system. Therefore, using this Ia+ LC frequency modulation system, we propose that GM-CSF is one example of a cytokine which may be involved in the regulation of Ia+ LC numbers in epidermis and that epidermal cells produce factors which can increase the number of Ia+ LC.

Animals↗

Minocycline-induced hyperpigmentation in leprosy.

A 36-year-old man was treated with dapsone, rifampicin and clofazimine for borderline lepromatous leprosy. After 9 months, his leprosy plaques became progressively more red and after 23 months, the clofazimine was stopped and he was given minocycline instead. Six weeks later, he developed blue-black pigmentation in his leprosy lesions. The histology was consistent with minocycline-induced hyperpigmentation. This is the first report of minocycline-induced pigmentation in leprosy. We suggest it is important to consider this side-effect before the administration of minocycline in leprosy, particularly if it is prescribed in place of clofazimine.

Adult↗

Epidermal Langerhans' cell induction of immunity against an ultraviolet-induced skin tumour.

Langerhans' cells (LC) have been shown experimentally to induce immune responses against many antigens; however, their role in the initiation of anti-tumour immunity has received little attention. This study examined the ability of murine epidermal LC to induce immunity to an ultraviolet radiation (UV)-induced skin tumour. Freshly prepared epidermal cells (EC) were cultured for 2 or 20 hr with granulocyte-macrophage colony-stimulating factor (GM-CSF), pulsed with an extract of the UV-13-1 tumour, then used to immunize naive syngeneic mice. Delayed type hypersensitivity (DTH) was elicited 10 days after immunization by injection of UV-13-1 tumour cells into the ear pinna, and measured 24 hr later. EC cultured with GM-CSF for 2 hr induced antitumour DTH, as did EC cultured for 20 hr without GM-CSF. Conversely, EC cultured for 2 hr without GM-CSF, or EC cultured for 20 hr with GM-CSF were unable to induce a DTH. Induction of immunity required active presentation of tumour antigens by Ia+ EC and was tumour specific. Thus Ia+ epidermal cells are capable of inducing anti-tumour immunity to UV-induced skin tumours, but only when they contact antigen in particular states of maturation.

Animals↗

CD4+ T lymphocyte infiltration correlates with regression of a UV-induced squamous cell carcinoma.

It is currently unknown which arm of the immune system is responsible for regression of tumours. We have studied the T lymphocytes infiltrating a spontaneously regressing murine squamous cell carcinoma during the growth, plateau and regression phases of tumour development. In the plateau phase, where tumour growth is partially controlled by the immune system so that tumour size remains static, there was a considerable influx of CD4+ cells into the tumour. There was also an increase in the number of cells expressing the receptor for interleukin 2 (IL-2R), indicating that these cells were probably activated. The number of CD4+ cells remained high during the regression phase, where immunological destruction exceeded tumour growth. In contrast, CD8+ cells were only present in low numbers, and did not change during growth or regression of the tumours. These results indicate that CD4+ cells are probably responsible for tumour destruction. Thus CD4+ T lymphocytes are able to mediate tumour rejection and should be given more consideration for immunotherapy.

Animals↗

Sunscreen protection of contact hypersensitivity responses from chronic solar-simulated ultraviolet irradiation correlates with the absorption spectrum of the sunscreen.

This study compares the ability of two ultraviolet (UV) B-absorbing sunscreens, 2-ethylhexyl p-methoxycinnamate (2-EHMC) and 2-ethylhexyl p-aminobenzoate (Padimate O), and two physical sunscreens, microfine titanium dioxide (MTD) and zinc oxide, to protect the skin immune system from chronic (4 weeks) solar-simulated UV irradiation. Mice were exposed to suberythemal doses of UV before assessing local and systemic immunosuppression and tolerance to a contact sensitizer. Using a UV protocol that induced local but not systemic immunosuppression or tolerance in BALB/c mice, it was shown that Padimate O made the immunosuppression worse, whereas 2-EHMC and MTD protected the immune system. When the cumulative dose was increased by 12.7%, causing systemic immunosuppression and tolerance, none of the sunscreens protected from immunosuppression, but 2-EHMC provided partial, and MTD gave complete protection from tolerance. To examine this apparent lack of protection from systemic immunosuppression, C3H/HeJ mice were used. These mice had a minimal erythema dose similar to that of the BALB/c mice but were systemically immunosuppressed, with only 44% of the UV dose required to immunosuppress BALB/c mice. 2-EHMC provided some protection, whereas MTD provided complete protection from systemic immunosuppression in C3H/HeJ mice. Hence, sunscreens can protect from local and systemic immunosuppression, although this protection is limited and is not related to the sun protection factor of the sunscreens or the minimal erythema dose of the mouse strain. Instead, protection seems to be related to the sunscreens' having a broad absorption spectrum.

4-Aminobenzoic Acid↗

A comparative study of isolutrol versus benzoyl peroxide in the treatment of acne.

Isolutrol is the active principle isolated from aqueous tissue extracts of deep sea shark liver and gall-bladder. A previous study has demonstrated the ability of isolutrol to reduce hyperseborrhoea, which provides a rationale for its use in the treatment of acne. We have performed a double-blind clinical trial on 70 patients to evaluate the efficacy and skin tolerance of isolutrol 0.15 g/100 mL (Ketsugo) in the treatment of mild to moderate acne when compared with 5% benzoyl peroxide lotion. The results from this study showed that both isolutrol and benzoyl peroxide significantly improved patients' acne by reducing the number of inflamed lesions. Isolutrol did not significantly reduce the numbers of non-inflamed lesions whereas benzoyl peroxide did. Fewer side effects were experienced by patients treated with isolutrol when compared with benzoyl peroxide. These results indicate that isolutrol may be a useful adjunct in the treatment of acne, particularly in patients with inflamed lesions.

Acne Vulgaris↗

Pustular psoriasis of pregnancy.

The case of an 18 year old woman who developed generalized pustular psoriasis of pregnancy in the 23rd week of her first pregnancy is reported. Treatment with topical therapies was unsuccessful and oral steroids were introduced with rapid response.

Administration, Oral↗

Paraneoplastic pemphigus triggered by radiotherapy.

Paraneoplastic pemphigus is a recently described autoimmune disease characterized by painful mucosal ulceration and polymorphous skin lesions in association with an underlying neoplasm. Distinct autoantibodies bind desmoplakin I, desmoplakin II, bullous pemphigoid antigen and an uncharacterized 190 kDa antigen. A case is presented of paraneoplastic pemphigus that developed after radiotherapy for non-Hodgkin's lymphoma in a 53 year old man. Multiple skin biopsies showed a lichenoid reaction without acantholysis. Immunofluorescence and mucosal biopsies were required to establish the correct diagnosis. Corneal opacities resembling lichenoid graft-versus-host disease and retinal haemorrhages, which developed in the patient, have not been previously documented. Despite high doses of immunosuppressive agents and plasmaphoresis, the patient eventually died from respiratory failure.

Acantholysis↗

Regression in basal cell carcinoma: an immunohistochemical analysis.

Spontaneous regression of some cutaneous tumours is well recognized, and is thought to result from an immunological response to the tumour. Regression has previously been noted in basal cell carcinomas, but no studies defining the role of the immune response in the regression of this malignancy have been performed. We have examined 45 primary basal cell carcinomas (BCCs) (20 nodular, 25 superficial) and identified the cellular phenotypes and activation states of the cells infiltrating primary regressing and non-regressing BCCs, by immunocytochemistry. We have found a significantly increased number of CD3+ and CD4+ T cells infiltrating regressing compared with non-regressing tumours, and the expression of interleukin-2 receptor (an early activation marker for T cells) was also increased. There were no significant differences in class II major histocompatibility complex (MHC), CD1, or macrophage antigen expression in these groups. These findings suggest that activated CD4+ cytokine-secreting cells are important in the regression of BCCs.

CD4-CD8 Ratio↗

Evidence that regression in keratoacanthoma is immunologically mediated: a comparison with squamous cell carcinoma.

Recent research observations suggest that the keratoacanthoma (KA) is a form of resolving squamous cell carcinoma (SCC). The mechanism by which this resolution takes place has not been fully explored, although it may have an immunological basis. To investigate this, we compared 15 clinically and histologically diagnosed KAs and 15 SCCs with regard to cellular infiltrate and keratin expression. We found that KAs have significantly higher numbers of CD3+ and CD4+ cells invading their epidermal component than SCCs. The T lymphocytes infiltrating KAs were more immunologically active, as greater numbers expressed the interleukin-2 receptor (IL-2R) than those in SCCs. It is of interest that CD36 was expressed by a significantly greater proportion of tumour cells within KAs than SCCs. This was also the case for the intercellular adhesion molecule ICAM-1, and the differentiation marker keratin 10. Overall, these findings suggest that KA regression is immunologically mediated, with activated (IL-2R+) CD4+ T lymphocytes and adhesion molecules playing a pivotal role in the immune response.

Aged↗

Evaluation of 0.75% metronidazole gel in acne--a double-blind study.

Metronidazole, an imidazole, is an antibiotic with established efficacy against anaerobic bacteria. To date, however, there are no published data concerning the efficacy of topical metronidazole in the treatment of acne. This randomized, double-blind prospective clinical study of 96 patients was performed to investigate the efficacy and tolerability of 0.75% metronidazole gel vs. placebo in the treatment of mild to moderate acne. The results of this study showed no significant benefit in using 0.75% metronidazole gel over placebo in reducing counts of inflamed and non-inflamed lesions of acne. There was also no statistically significant difference between the two groups at any stage in the trial when skin tolerability was assessed.

Acne Vulgaris↗