Biomedical subjects
Publications and source records attributed to G I Stables.
Nail apparatus melanoma (or subungual melanoma) is rare and accounts for only 1.4% of all cutaneous melanomas in the United Kingdom. We report the use of fixed-tissue Mohs micrographic surgery to treat a biopsy-proven Clark level I in situ nail apparatus melanoma, presenting with diffuse longitudinal melanonychia.
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Large patches of Bowen's disease (intraepidermal carcinoma in situ) can be difficult to treat by conventional methods. Photodynamic therapy (PDT) uses the combination of a photosensitizer, which preferentially accumulates in malignant cells, and photoactivation by visible light to kill the malignant cells. 5-aminolaevulinic acid (ALA) PDT uses excess exogenous ALA, which produces, via the haem synthesis pathway, a build up of the photosensitizer protoporphyrin IX. We describe the use of topical ALA PDT to treat three patients with three especially large patches of Bowen's disease. Following two treatments all three lesions achieved a complete clinical and histological response with a good cosmetic result. ALA PDT is a simple, effective and well tolerated treatment for large patches of Bowen's disease.
We have investigated the clinical response of 22 patients with plaque psoriasis to photodynamic therapy using topical application of 5-aminolaevulinic acid followed by a single exposure to broad-band visible radiation. Light doses in the range 2-16 J/cm2 delivered at dose of 10-40 mW/ cm2 resulted in a variable clinical response. Seven (35%) patients showed clearing of psoriasis at some treated sites. The intensity of protoporphyrin IX fluorescence was recorded before, during and after treatment. Pre-illumination fluorescence intensity varied considerably between sites on the same patient and between patients. Protoporphyrin IX fluorescence recovered and persisted after treatment for up to 14 days and became higher than preillumination levels at 25% of sites. The rate of protoporphyrin IX photo-oxidation during treatment was proportional to both initial fluorescence intensity and incident light dose rate and was almost complete after 16 J/cm2. We have defined the photodynamic dose as the product of time-dependent protoporphyrin IX concentration and light dose and demonstrated that only in those patients who showed clearance of psoriasis was there a relationship between photodynamic dose and clinical response. Discomfort ranged from stinging through to burning, was significant in some patients and tended to be more severe with increasing photodynamic dose but was not predictable. Efficacy may improve by achieving consistent protoporphyrin IX levels or by using multiple treatments.
The success reported for the treatment of superficial skin carcinomas by photodynamic therapy with topical application of the photosensitizer precursor 5-aminolevulinic acid has therapeutic implications for the treatment of other skin disorders. This paper describes the accumulation of the photosensitizing agent protoporphyrin IX in areas of plaque psoriasis by monitoring of the fluorescence emission induced by low-intensity laser excitation at 488 nm. We present results from 15 patients with a total of 42 plaques and show that the characteristic fluorescence emission of protoporphyrin IX increases in intensity within the 6-h period following application of 5-ami-nolevulinic acid, suggesting that there is a potential for superficial photodynamic therapy. The rate of increase and maximum intensity of fluorescence emission was not directly related to the applied quantity of the precursor. The variability of the fluorescence intensity was as great between plaques at different sites on the same patient as between different patients. Also, the effect of plaque occlusion following application appeared insignificant. Although there was only limited enhancement of emission from areas of skin surrounding the plaque, a significant buildup of sensitizer was detected after several days in some areas of psoriasis that received no application.
92 children (45 girls, 47 boys), mean age 9.3 years (3-14.75), were referred to the Contact Dermatitis Investigation Unit, Belvidere Hospital, Glasgow, for patch testing during the period 1979-93 for the investigation of allergic contact dermatitis (ACD). The diagnoses at the time of referral were atopic dermatitis (45), non-atopic with localized dermatitis (26), juvenile plantar dermatosis (15), orofacial granulomatosis (2), vaccination reaction (2) and atypical psoriasis (2). In total, there were 55 positive reactions in 30 children. The commonest allergens were metals (18), fragrances (11) and rubber compounds (6). The patient groups with the highest yield of positive patch tests were those patients with atopic dermatitis who had a good history of a precipitating contact factor (4/5), and non-atopic patients with dermatitis of hand and/or feet (7/14). Our findings suggest that allergic contact dermatitis is more common in children than generally appreciated and that patch testing is a practicable and clinically worthwhile procedure in children.
Normal p53 protein protects the genome after DNA damage by delaying replication and allowing DNA repair. mdm-2 is a recently discovered protein that controls p53 activity by binding to and inactivating p53 protein. A negative feedback loop has been suggested in which p53 induces mdm-2 expression. We have shown that doses of ultraviolet B radiation that cause mild sunburn clinically, produce thymine dimers in keratinocytes detectable by immunocytochemistry. This causes an elevation of p53 protein without a concomitant p53-mediated induction of mdm-2.
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We report a child with lupus erythematosus secondary to type 2 hereditary angio-oedema (HAE). Reduced levels of free protein S were found. Total protein S, and C4 binding protein (C4bp) were normal, and there was no evidence of anticardiolipin antibodies or lupus anticoagulant. We postulate that reduced levels of C4, secondary to C1 inhibitor deficiency, resulted in increased binding of protein S to C4bp, leading to reduced levels of free protein S and thus functional deficiency of protein S.
We present a patient with established histiocytosis who developed dysphagia, retching, regurgitation, hoarseness and stridor. These symptoms were managed with carbon dioxide laser vaporization, electively on three occasions, and once as an urgent procedure, while awaiting radiotherapy, to control her airway. Histiocytosis is a rare cause of a number of otolaryngological syndromes, but there has been no previous record of this disease causing laryngopharyngeal symptoms. This paper discusses the classification of histiocytosis, and describes our management of this rare and intriguing case.
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The case is reported of a 56-year-old female who over 18 months developed a symmetrical eruption of hundreds of bluish-red papules, a small number of which have spontaneously resolved. The clinical and histopathological findings were compatible with the diagnosis of generalized eruptive histiocytoma. The ultrastructural findings in this case suggest that this condition which is in the non-X group of histiocytic disorders is closely related to histiocytosis X.
During the 9-year period from 1982 to 1991, 72 patients with melanoma were treated with a 5-day quadruple drug chemotherapy regime (BELD) comprising bleomycin, vindesine (Eldesine), CCNU (Lomustine) and DTIC. Forty-three patients had stage III melanoma, 34 of whom had evaluable disease. Of these 34, six (17.6%) achieved a complete response (CR), eight (23.5%) had a partial response (PR), five (14.7%) had stabilized disease (SD) and 15 (44.1%) had progressive disease (PD). Overall median survival of stage III melanoma patients was 38 weeks. Median survival of responders (CR + PR) was 47 weeks and 21 weeks for non-responders (SD + PD) (P < 0.005). Median follow-up time was 38 weeks. Following these encouraging results, 30 patients with stage II melanoma received BELD chemotherapy as adjuvant therapy after regional node dissection and clearance. Adjuvant BELD chemotherapy did not alter survival in these patients. BELD combination chemotherapy is well-tolerated, the main problems being nausea, vomiting, and leucopenia. We have maintained a combined response rate (CR + PR) of 41.1% for stage III disease. This is comparable with other combination chemotherapy regimes, which have as yet not been superseded by the newer biological therapies.
We report the case of a 41-year-old man who presented with hepatic amoebiasis 18 months after visiting the Far East. His progress was initially complicated by a bronchohepatic fistula which was further complicated by secondary bacterial infection. The fistula persisted and only resolved following percutaneous catheter drainage, thereby avoiding open surgery.