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Biomedical subjects

R A Graham-Brown

Publications and source records attributed to R A Graham-Brown.

At least 19 recordsLinked to original sources
PubMed2000

Cyclosporin for severe childhood atopic dermatitis: short course versus continuous therapy.

Cyclosporin (CyA) has been shown to be highly effective and well tolerated in the short-term treatment of severe childhood atopic dermatitis; however, there is limited experience in its longer-term use. The aim of this study was to compare multiple short courses of CyA with continuous therapy for 1 year, with respect to efficacy, safety, tolerability and quality of life. Children aged 2-16 years, with a diagnosis of severe atopic dermatitis refractory to topical steroid therapy, were randomly assigned to receive short course therapy (multiple courses of 12 weeks) or continuous therapy. The starting dose and maximum dose for all patients was 5 mg/kg per day. Disease activity was monitored using the Six Area Six Sign Atopic Dermatitis score and the 'Rule of Nines' area score. Pruritus, sleep disturbance and irritability were measured using visual analogue scales, and topical therapy was monitored. Safety measurements included monitoring of serum creatinine, blood pressure and adverse events. Forty patients were included in the efficacy analysis, 21 of whom were randomized to the short course group (of whom six were withdrawn) and 19 to the continuous group (of whom five were withdrawn). Significant improvements were seen in all efficacy parameters at every time-point. There were no significant differences between groups, although the improvement was more consistent in the continuous arm. In the short course arm, 7 out of 21 patients could be managed by at least two short courses. The remaining 14 patients includes 12 who could not be controlled by at least two short courses, one patient who failed to return after week 12 and another patient who was withdrawn at week 4 due to an adverse event. Quality of life improved for both the children and their families. Tolerability was considered good or very good in at least 80% of the patients at week 12 and at the end of the study. No clinically significant change was seen in mean serum creatinine and no change was seen in mean blood pressure in either group. CyA is effective in controlling severe atopic dermatitis in children over a 1-year period and is well tolerated. More consistent control is achieved with continuous treatment; however, short course therapy was adequate for some patients, indicating that treatment should be tailored to the individual patient's needs. Short course treatment may produce prolonged remission in some cases and reduce the cumulative exposure to the drug.

Adolescent↗
PubMed1999

False negative clinical diagnoses of malignant melanoma.

The false negative rate for the clinical diagnosis (FNR) for malignant melanoma is reported to be of the order of 20-50%. The aim of this study was to investigate possible predictor variables for FNR, with particular reference to the features and score of the seven-point check-list within the total population (778) of histologically proved malignant melanomas presenting in Leicestershire between 1982 and 1996. The FNR was 18.5%. The check-list would have failed as a referral indication in only 0.8-1. 1% of the lesions. The major check-list features occurred more commonly than the minor features, excepting size >/= 7 mm, confirming the diagnostic importance of the major criteria. The FNR was unaffected by age or sex. More rarely involved sites had higher rates (31-42%), and the face was a particularly difficult diagnostic site. Clinical features of lesions associated with a higher FNR were lack of irregular pigmentation and shape, altered sensation, the presence of inflammation and size < 7 mm. The FNR was inversely related to the total score and major feature score, but directly related to the minor score. The minor features, in addition to the major features, are potentially valuable in avoiding false negative diagnoses and we suggest their retention as part of the check-list. There was only one patient, in whom the diagnosis of melanoma was initially missed and who was not biopsied on presentation to hospital, who re-presented after 1 year. However, the study illustrates the importance of avoiding a false negative diagnosis as there was marked delay in the excision of such lesions.

Adult↗
PubMed1999

The value of an aide memoire in the dermatology clinic.

A randomized study was undertaken to investigate the effectiveness of a chart as an aid to memory illustrating the topical medication most frequently prescribed both in the dermatology clinic, and in general practice. One hundred subjects, half new referrals and half follow-ups, were recruited and asked to recall all of the topical preparations that had previously been prescribed for this condition. They were then asked to consult the chart, and any additional medication recognized at this time was noted, along with any clarification of formulation and strength where possible. Despite some limitations, our chart proved to be of considerable value. Thirty-eight patients could identify between three and eight additional preparations. Overall, the mean number of additional preparations recalled per patient was two. Clarification of strength and formulation was achieved by 21 patients. Eight charts were used, and provided additional information at consultation in 87% of subjects interviewed.

Administration, Topical↗
PubMed1998

The effect of the introduction of a pigmented lesion clinic on the interval between referral by family practitioner and attendance at hospital.

The value of pigmented lesion clinics (PLCs) for the early detection and treatment of malignant melanoma has been questioned. We have examined the effect of the introduction of a PLC on the referral interval between patients with melanoma presenting to their general practitioner (GP) and their attendance at hospital. The case notes of all patients presenting with melanoma in Leicestershire between 1984 and 1994 were reviewed. There was a significant initial reduction in the mean referral interval following the introduction of the PLC from 27.9 days (SEM = 6.6) in 1984 to 11.3 (2.3) days in 1987 (P < 0.01). However, the referral interval gradually rose over the following 7 years to a mean of 20.4 (4.4) days in 1994, which was not significantly better than the 1985/86 level. The increase in the referral interval was due to a greater percentage of melanomas being referred to clinics other than the PLC. Only 48% of melanomas were referred to the PLC in 1994 compared with 70% in 1987. We also reviewed the referral letters for those patients presenting in 1991 and 1994, and decided, on the basis of the content of the letter, whether the GP had suspected the diagnosis of melanoma. More than 50% of the melanomas were correctly diagnosed by the GP, but only half of these were then appropriately referred to the PLC. We believe that PLCs are of value in the early diagnosis and treatment of melanoma, but only if they are appropriately utilized by GPs.

England↗
PubMed1997

Sweet's syndrome and malignancy in the U.K.

Acute febrile neutrophilic dermatosis (Sweet's syndrome) is reported to be a marker for underlying malignancy. Much of the evidence for this is based on case reports, small series of cases and reviews of the literature. In order to clarify the association with malignancy and determine the common clinical features of Sweet's syndrome, we reviewed the case notes of patients presenting to six dermatology units in the U.K. Eighty-seven cases of histologically proven Sweet's syndrome were reviewed. Fourteen patients (16%) developed associated malignancy, predominantly haematological, two patients (2%) had a history of previous malignancy and four patients (5%) had premalignant conditions (monoclonal gammopathy, two: myelodysplasia, two). Malignancy developed up to a year after presentation with Sweet's syndrome. Patients with associated malignancy were more likely to be anaemic (P < 0.01) at presentation, had a lower mean platelet count (207 x 10(9)/L vs. 332 x 10(9)/L; P < 0.003) and were, on average, older (59 years vs. 49 years; P = 0.002). Contrary to previous reports, a greater percentage of females developed malignancy than males.

Adolescent↗
PubMed1997

Long-term efficacy and safety of cyclosporin in severe adult atopic dermatitis.

A prospective, open, multicentre study was performed to investigate the efficacy and safety of long-term treatment with cyclosporin in adults with severe atopic dermatitis. Subjects were treated for a maximum of 48 weeks. For the first 8 weeks, cyclosporin was administered at 2.5 mg/kg per day. The dose was then adjusted according to response. Disease activity was monitored using the six-area, six-sign score and the proportion of skin involved. Pruritus and sleep disturbance were assessed using four-point scales. Response was further evaluated on a five-point scale. Adverse events, blood pressure and serum biochemistry were monitored. Tolerability was assessed on a five-point scale. One hundred subjects were enrolled and 65 completed 48 weeks of treatment. Withdrawals occurred due to remission (three), inadequate response (seven), protocol violations (11) and adverse events (14, of which seven were probably treatment related). Cyclosporin produced rapid and highly significant improvements in all indices of disease activity. Sixty-five subjects considered that they had shown a considerable improvement or complete clearance of disease. Most patients relapsed after cessation of treatment, but neither signs nor symptoms had returned to baseline severity 8 weeks later. Blood pressure and serum creatinine levels increased slightly, and in one subject renal impairment was a major factor contributing to withdrawal of the drug. Overall, 85 subjects rated the tolerability of cyclosporin as good or very good. The results indicate that cyclosporin has a place in the long-term treatment of severe atopic dermatitis provided that appropriate patients are selected and careful monitoring is performed.

Adolescent↗
PubMed1997

Etretinate may work where acitretin fails.

Acitretin (Ro 10-1670, Neotigason), a second-generation monoaromatic retinoid, is the main acid derivative and active metabolite of etretinate (Ro 10-9359, Tigason). Three patients who were unresponsive to treatment with acitretin but who responded to etretinate are reported. Twenty-nine patients in the U.K. are currently receiving etretinate on a named-patient basis. Possible explanations for the functional discrepancy between the two drugs are discussed.

Acitretin↗
PubMed1997

A possible explanation for the increased referral of atopic dermatitis from the Asian community in Leicester.

The population of the city of Leicester contains, in addition to the 'native' population, a large immigrant 'Asian' community originating from the Indian subcontinent. Among referrals to our department, atopic dermatitis (AD) was 3,3 times more common in Asians. We therefore performed a study based on a cohort of consecutive births in Leicester hospitals to investigate the possible ethnic difference in prevalence and to examine possible reasons for an ethnic difference in referral pattern. Parents of 1,800 children were asked at the time of the birth to allow their child to be entered on a register. A year later, parents of a sample of 499 of these children, 158 Asian and 341 non-Asian, were invited for interview and for examination of the children. A total of 413 children were examined. The overall point prevalence of AD was 10.7% (95% confidence interval, 7.7%-13.7%). There was no significant ethnic difference. However, a history of eczema in a first degree relative was found in 14.2% of Asian subjects and 35.1% of non-Asians (P < 0.0001, chi-square test). The data suggest the increased referrals to our clinic from the Asian community may result from a lower level of familiarity with AD.

Adult↗
PubMed1997

Predictors of atopic dermatitis in Leicester children.

There is little contemporary data available on the prevalence of atopic dermatitis (AD) or the risk factors associated with this disease. We therefore performed a prospective study of 1-year-old children based on a cohort of consecutive births in Leicester hospitals. Parents of 1800 children born between March and May 1992 were asked at the time of the birth to allow their child to be entered on a register. A sample of 499 of these children were invited for interview and examination at 1 year of age. Data were collected on gestational maturity, birth weight, feeding pattern, family history of eczema and atopy, social class and other parameters. Four hundred and thirteen of the 499 children were examined (83%). The overall point prevalence of AD was 10.7% (95% confidence interval, 7.7%-13.7%). The most significant risk factor for a child developing AD was a parental history of eczema.

Adult↗
PubMed1997

Treatment of psoriasis with intermittent short course cyclosporin (Neoral). A multicentre study.

A 1 year, prospective multicentre study was performed to investigate the efficacy and safety of intermittent treatment with cyclosporin in psoriasis vulgaris. Subjects received cyclosporin (Neoral) 5 mg/kg per day until achieving 90% reduction in area affected, or for a maximum of 12 weeks. Those failing to demonstrate a satisfactory response were withdrawn. When further treatment was required, cyclosporin was recommenced. This cycle was repeated up to three times. Psoriasis activity was recorded using the area affected and sign scores for erythema, scaling and infiltration. Overall assessments of response and tolerability were recorded. Forty-one subjects, mean age 36, mean PASI 12.8, entered the first treatment period. Thirty-three received a second period of treatment and 16 a third. Eighteen failed to complete the study as planned: five were withdrawn due to adverse events, four due to treatment failure and nine due to protocol violations. At the end of each treatment period, significant improvements were seen in all efficacy parameters. Overall response was graded as 'considerable improvement' or 'minimal or no symptoms', by over 80% of subjects and investigators. Median intervals to relapse for subjects remaining in the study were 72 days (range 28-329) and 53 days (range 14-141) after periods 1 and 2, respectively. There were significant increases in mean serum creatinine and blood pressure during each treatment period. However, there were no significant differences in either parameter between baseline and the final follow-up visit. At the end of each treatment period, overall tolerability of the treatment was considered 'good' or 'very good' by over 80% of subjects and investigators.

Adult↗
PubMed1996

Cyclosporine in severe childhood atopic dermatitis: a multicenter study.

BACKGROUND: Severe atopic dermatitis (AD) remains difficult to treat. Cyclosporine is effective in adults but has not previously been investigated in children with AD. OBJECTIVE: The aims were to investigate the efficacy, safety, and tolerability of cyclosporine in severe refractory childhood AD. METHODS: Subjects 2 to 16 years of age were treated for 6 weeks with cyclosporine, 5 mg/kg per day, in an open study. Disease activity was monitored every 2 weeks by means of sign scores, visual analogue scales for symptoms, and quality-of-life questionnaires. Adverse events were monitored. Efficacy and tolerability were assessed with five-point scales. RESULTS: Twenty-seven children were treated. Significant improvements were seen in all measures of disease activity. Twenty-two showed marked improvement or total clearing. Quality of life improved for both the children and their families. Tolerability was considered good or very good in 25 subjects. CONCLUSION: Cyclosporine may offer an effective, safe, and well-tolerated short-term treatment option for children with severe AD.

Administration, Oral↗