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Biomedical subjects

N B Simpson

Publications and source records attributed to N B Simpson.

At least 19 recordsLinked to original sources
PubMed2005

Randomised controlled multiple treatment comparison to provide a cost-effectiveness rationale for the selection of antimicrobial therapy in acne.

OBJECTIVES: To determine the relative efficacy and cost-effectiveness of five of the most commonly used antimicrobial preparations for treating mild to moderate facial acne in the community; the propensity of each regimen to give rise to local and systemic adverse events; whether pre-existing bacterial resistance to the prescribed antibiotic resulted in reduced efficacy; and whether some antimicrobial regimens were less likely to give rise to resistant propionibacterial strains. DESIGN: This was a parallel group randomised assessor-blind controlled clinical trial. It was a pragmatic design with intention-to-treat analysis. All treatments were given for 18 weeks, after a 4-week treatment free period. Outcomes were measured at 0, 6, 12 and 18 weeks. SETTING: Primary care practices and colleges in and around Nottingham and Leeds, and one practice in Stockton-on-Tees, England. PARTICIPANTS: Participants were 649 people aged 12--39 years, all with mild to moderate inflammatory acne of the face. INTERVENTIONS: Study participants were randomised into one of five groups: 500 mg oral oxytetracycline (non-proprietary) twice daily (b.d.) + topical vehicle control b.d.; 100 mg oral Minocin MR (minocycline) once daily (o.d.) + topical vehicle control b.d.; topical Benzamycin (3% erythromycin + 5% benzoyl peroxide) b.d. + oral placebo o.d.; topical Stiemycin (2% erythromycin) o.d. + topical Panoxyl Aquagel (5% benzoyl peroxide) o.d. + oral placebo o.d., and topical Panoxyl Aquagel (5% benzoyl peroxide) b.d. + oral placebo o.d. (the active comparator group). MAIN OUTCOME MEASURES: The two primary outcome measures were: (1) the proportion of patients with at least moderate self-assessed improvement as recorded on a six-point Likert scale, and (2) change in inflamed lesion count (red spots). RESULTS: The best response rates were seen with two of the topical regimens (erythromycin plus benzoyl peroxide administered separately o.d. or in a combined proprietary formulation b.d.), compared with benzoyl peroxide alone, oxytetracycline (500 mg b.d.) and minocycline (100 mg o.d.), although differences were small. The percentage of participants with at least moderate improvement was 53.8% for minocycline (the least effective) and 66.1% for the combined erythromycin/benzoyl peroxide formulation (the most effective); the adjusted odds ratio for these two treatments was 1.74 [95% confidence interval (CI) 1.04 to 2.90]. Similar efficacy rankings were obtained using lesion counts, acne severity scores and global rating by assessor. Benzoyl peroxide was the most cost-effective and minocycline the least cost-effective regimen (ratio of means 12.3; difference in means -0.051 units/GBP, 95% CI -0.063 to -0.039). The efficacy of oxytetracycline was similar to that of minocycline, but at approximately one-seventh of the cost. For all regimens, the largest reductions in acne severity were recorded in the first 6 weeks. Reductions in disability scores using the Dermatology Quality of Life Scales were largest for both topical erythromycin-containing regimens and minocycline. The two topical erythromycin-containing regimens produced the largest reductions in the prevalence and population density of cutaneous propionibacteria, including antibiotic-resistant variants, and these were equally effective in participants with and without erythromycin-resistant propionibacteria. The clinical efficacy of both tetracyclines was compromised in participants colonised by tetracycline-resistant propionibacteria. None of the regimens promoted an overall increase in the prevalence of antibiotic-resistant strains. Systemic adverse events were more common with the two oral antibiotics. Local irritation was more common with the topical treatments, particularly benzoyl peroxide. Residual acne was present in most participants (95%) at the end of the study. CONCLUSIONS: The response of mild to moderate inflammatory acne to antimicrobial treatment in the community is not optimal. Only around half to two-thirds of trial participants reported at least a moderate improvement over an 18-week study period; extending treatment beyond 12 weeks increased overall benefit slightly. Around one-quarter dropped out when using such treatments, and 55% sought further treatment after 18 weeks. Topical antimicrobial therapies performed at least as well as oral antibiotics in terms of clinical efficacy. Benzoyl peroxide was the most cost-effective and minocycline the least cost-effective therapy for facial acne. The efficacy of all three topical regimens was not compromised by pre-existing propionibacterial resistance. Benzoyl peroxide was associated with a greater frequency and severity of local irritant reactions. It is suggested that the use of a combination of topical benzoyl peroxide and erythromycin gives less irritation and better quality of life. There was little difference between erythromycin plus benzoyl peroxide administered separately and the combined proprietary formulation in terms of efficacy or local irritation, except that the former was nearly three times more cost-effective. The data on cost-effectiveness, and outcomes in patients with resistant propionibacterial floras, did not support the first line use of minocycline for mild to moderate inflammatory acne of the face. Three priority areas for clinical research in acne are: defining end-points in acne trials (i.e. what is a satisfactory outcome?); developing and validating better patient-based measures for assessing treatment effects on facial and truncal acne; and exploring patient characteristics that may modify treatment effects (efficacy and tolerability).

Acne Vulgaris↗
PubMed2004

NBCCS secondary to an interstitial chromosome 9q deletion.

Naevoid basal cell carcinoma syndrome (NBCCS) or Gorlin syndrome is a rare autosomal dominant cancer disorder. The Gorlin's gene, Patched 1 (PTCH1), maps to Chromosome 9q. Germline mutations of PTCH1 occur in patients with NBCCS. The subsequent loss of the remaining allele results in cancer formation. We present a patient with NBCCS and additional phenotypic features including severe developmental delay, short stature and hypotelorism who was found to have an interstitial chromosome 9q deletion. The NBCCS phenotype in our patient occurred as a result of PTCH1 deletion in contrast with an inherited mutation of this gene.

Adult↗
PubMed1997

Correlation of clinical, endocrine and molecular abnormalities with in vivo responses to high-dose testosterone in patients with partial androgen insensitivity syndrome.

OBJECTIVE: To investigate the responses of two patients previously diagnosed as Reifenstein's syndrome to graded high-dose testosterone in terms of hormone levels, nitrogen balance and sebum secretion and to attempt to correlate these parameters with the properties of their androgen receptors and mutations in the androgen receptor gene. DESIGN: Nitrogen balance was determined by comparing controlled nitrogen intake to the amount excreted. Sebum excretion was measured on the forehead. Patients were studied during control periods (no treatment) and during administration of testosterone propionate. Blood samples were used as a source of genomic DNA and to measure peripheral hormone levels; androgen receptor binding was determined using genital skin fibroblasts. PATIENTS: Two patients of XY karyotype, with ambiguous external genitalia and problems of testicular descent who had required mastectomy as teenagers. Normal male controls of proven fertility. MEASUREMENTS: Nitrogen balance, sebum excretion rate and peripheral hormone levels (testosterone, dihydrotestosterone, LH and FSH) were studied before and after testosterone therapy (1 or 5 mg/kg/day). Genomic DNA was extracted from peripheral blood leucocytes and regions of the androgen receptor gene amplified by polymerase chain reaction using pairs of specific primers. Mobility of amplified DNA from patients was analysed on denaturing gradient acrylamide gels and fragments differing in mobility from those of normal controls were sequenced. Fibroblasts were cultured from scrotal skin biopsies and androgen receptor binding parameters, subcellular localization and up-regulation were determined. RESULTS: Testosterone therapy resulted in raised plasma testosterone, dihydrotestosterone and oestradiol in both patients. In patient 1 (lesser genital abnormality), LH was suppressed by 5 mg/kg/day testosterone to the upper limit of the normal range but FSH remained low normal. Both LH and FSH were suppressed by testosterone treatment in patient 2 (greater genital abnormality). Nitrogen retention was increased in both patients (4.2 and 3.0 g/24 h respectively); sebum excretion rate increased to normal in patient 1 but showed no change in patient 2. Mutations in the androgen receptor gene were identified in both patients. In patient 1 a single nucleotide change from adenosine to guanosine resulted in the substitution of glycine for glutamic acid at position 772 within the hormone binding domain of the receptor. In patient 2 a single nucleotide mutation from guanosine to adenosine resulted in the substitution of lysine for arginine at position 608 (exon 3) situated in the second zinc finger of the DNA binding domain. Both patients had a normal number of androgen binding sites in genital skin fibroblasts but those in patient 1 showed reduced binding affinity and rapid dissociation of receptor/ligand complexes while those in patient 2 showed defective nuclear localization. CONCLUSION: In patients with partial androgen insensitivity syndrome the type of androgen receptor mutation and responses to short-term androgen treatment can be correlated with the individual's potential to virilize. If there is a mutation in the androgen receptor DNA binding domain the patient may show little ability to virilize either spontaneously at puberty or after androgen treatment. Sebum excretion appears to be more discriminating than nitrogen balance or gonadotrophin suppression as an index of tissue response to androgens.

Adult↗
PubMed1997

Systemic lupus erythematosus complicating complement type 2 deficiency: successful treatment with fresh frozen plasma.

We report a man who presented in 1981 at the age of 30 with cutaneous lupus erythematosus (LE), which was resistant to a range of treatments over the subsequent 11 years. In 1991 he suffered fits, dysphasia and agitated depression, and in 1992 a severe septicaemic illness. Systemic LE was diagnosed, and investigation showed homozygous complement type 2 deficiency (C2d). Over a period of 30 months he has received 6 weekly fresh frozen plasma. Since starting this treatment his cutaneous disease has resolved and his depression, verbal fluency and psychomotor scores improved. We have not observed any adverse effects to this treatment and suggest it should be considered in similar patients.

Adult↗
PubMed1996

Sebaceous hyperplasia in organ transplant recipients: shared aspects of hyperplastic and dysplastic processes?

BACKGROUND: Patients receiving kidney or heart transplants are subject to a wide range of cutaneous changes attributed largely to the immunosuppression required to prevent rejection of their transplant. In addition to infection, they have an increased incidence of dysplastic lesions, some of which are malignant. OBJECTIVE: Our purpose was to determine the incidence of sebaceous hyperplasia in heart and kidney transplant recipients and its association with neoplasia. METHODS: Patients undergoing heart transplantation from a single transplant center were examined during a 30-month screening period to establish the prevalence of cutaneous abnormalities. RESULTS: Sixteen of 104 (16%) heart transplant recipients had sebaceous hyperplasia in comparison with 1% of an age- and sex-matched control group. Those with sebaceous hyperplasia did not have a significantly higher incidence of hypertrichosis than those without sebaceous hyperplasia. CONCLUSION: Sebaceous hyperplasia is seen in heart transplant recipients. It does not appear to be connected with hypertrichosis, in which it is believed that the pilosebaceous unit is the target of the direct effect of cyclosporine. We propose that the development of sebaceous hyperplasia is related to the process of dysplastic epithelial proliferation in transplant recipients.

Child↗
PubMed1995

Reduced experimental contact sensitivity in squamous cell but not basal cell carcinomas of skin.

Basal cell carcinomas (BCC) and squamous cell carcinomas (SCC) show clinical and epidemiological differences not accounted for by different ultraviolet radiation exposure. We have studied experimentally induced contact sensitivity to dinitrochlorobenzene by measuring increases in skin-fold thickness. Patients (n = 37) with squamous tumours had impaired responses compared with controls (33) and patients with BCCs (31) (mean increase 4.5 vs 7.8 and 8.6 mm, respectively; p = 0.002). This diminished immunological response may be causally related to the development of SCC. Because glutathione S-transferase (GST) metabolises dinitrochlorobenzene and polymorphisms of GST are associated with multiple skin tumours, variations in GST may underlie these differences.

Basal Cell Carcinoma↗
PubMed1995

Treatment of basal cell carcinoma by dermatologists in the United Kingdom. British Association of Dermatologists Audit Subcommittee and the British Society for Dermatological Surgery.

Details of presentation and treatment were obtained prospectively by questionnaire for 1366 patients with basal cell carcinoma, first attending under the care of 166 consultant dermatologists in the U.K., during a 2-week period. One thousand five hundred and ninety-seven tumours were reported in these patients (median age 71 years). Most were situated on the head and neck, and their median size was 9 mm. Excision was the most common treatment used in 58% of tumours, curettage and cautery was used in 24%, cryotherapy in 8%, and radiotherapy in 8%. On average, one in four tumours were referred to other specialists for treatment (range 0-70%). Very few patients (2%) were referred to a combined dermatology/radiotherapy/plastic surgery clinic, calling into question its value and availability. There was considerable variation in practices between dermatologists, demonstrating a clear need for individual, local audit of the management of this common dermatological problem. The data collected in this study form a suitable measure with which local performance may be compared.

Adolescent↗
PubMed1995

Guidelines for the management of chronic venous leg ulceration. Report of a multidisciplinary workshop. British Association of Dermatologists and the Research Unit of the Royal College of Physicians.

This document is the product of a multidisciplinary workshop held in November 1991 between the audit subcommittee of the British Association of Dermatologists and the Research Unit of the Royal College of Physicians. Participants included dermatologists, vascular surgeons, general practitioners, community nurses and physicians involved in care of the elderly. The text is based on papers submitted to, and presented and discussed at, the workshop, and on comments received in response to subsequent wide dissemination of the proceedings to speciality associations. Participants in the workshop, and contributors to the guidelines are: Dr B. R. Allen (Nottingham), Sister S. Bainsborough (Exeter), Professor K. Burnand (London), Professor D. Burrows (Belfast), Mr M. J. Callam (Bedford), Dr G. W. Cherry (Oxford), Dr R. P. R. Dawber (Oxford), Dr W. S. Douglas (Airdrie), Dr A. Y. Finlay (Cardiff), Dr D. Gawkrodger (Sheffield), Dr D. J. Gould (Truro), Dr A. Hopkins (Royal College of Physicians, London), Dr D. McGibbon (London), Dr A. M. Middleton (London), Dr L. Millard (Nottingham), Dr L. Rhodes (Liverpool), Professor T. J. Ryan (Oxford), Dr N. B. Simpson (Newcastle), Dr F. D. Skerrett (Fowey), Dr J. M. Sowden (Nottingham), Miss L. A. Stone (London), Dr R. Williams (Rhyl). Papers presented to the workshop (copies available from the Royal College of Physicians of London): 1. Callam M. J. Epidemiology, natural history and rate of recurrence of leg ulcers. 2. Ryan T. J. Pathology of venous leg ulcers. 3. Gould D. J. Assessment of severity; process and outcomes of care. 4. Millard L. The role of infection. 5. Cherry G. Treatment of known effectiveness. 6. Burnand K. Indications for surgical treatment.

Aged↗
PubMed1995

Acute severe bronchoconstriction precipitated by coal tar bandages.

We report the occurrence of severe symptomatic bronchoconstriction in an atopic asthmatic subject following the application of coal tar bandages. Investigations showed that this was likely to have been caused by inhalation of coal tar vapour. We suggest that coal tar preparations should be used with caution in asthmatic subjects.

Acute Disease↗
PubMed1994

Follicular keratoses at amputation sites.

We describe two patients with painful follicular keratoses at lower limb amputation sites. Subsequent examination of 31 amputees revealed evidence of keratoses in four of 28 patients with lower limb stumps. Two of the four affected subjects experienced stump pain exacerbated by weight-bearing. This problem is not well documented. Local treatment measures may be ineffective. Painful stump follicular keratoses may be a cause of significant morbidity in lower limb amputees, and may be the result of an ill-fitting prosthesis.

Adult↗
PubMed1993

Medical audit--need for a positive commitment.

To assess the effectiveness of a case note audit in two dermatology units, the effect of policy changes in clinical practice, made following the identification of deficiencies in practice by an initial audit in 1987, were evaluated 2 years later by repeating the audit process, i.e. 'completing the audit circle'. The case notes of 200 new referrals of patients with psoriasis were audited, using a criteria set of 18 questions devised by a group of 66 dermatologists, in 1987 and again in 1989. Following the initial audit in 1987, policy changes were made at one centre (B) but not at the other (A). In the centre where no policy changes were agreed (A) there was no improvement in record keeping when re-audited in 1989. In centre (B), where a number of policy decisions were taken and protocols established, there was a highly significant improvement in record keeping (60% satisfactory completion of the criteria set in 1987 increased to 74% in 1989, P < 0.0001). Doctors in training grades performed best and were most responsive to the policy changes. The effectiveness of a criterion-based audit depends on a commitment to change, where indicated, and regular reinforcement of new policies at all levels of medical staff.

Hospitalization↗
PubMed1992

Oral presentation of pemphigus vulgaris and its response to systemic steroid therapy.

This article reviews our experience during a 20-year period with patients with oral lesions of pemphigus vulgaris. Of the 30 patients, 20 were women and 10 were men, with an age range of 24 to 68 years. The soft palate was involved in 80% of cases at initial presentation. Direct immunofluorescence studies were positive for IgG in the intercellular region in all cases where lesional tissue was histologically studied. Systemic steroid therapy alone controlled the disease in 24 patients, one patient was given no treatment, and the remaining five required additional treatment with either azathioprine, cyclophosphamide, or gold. Steroid therapy was continued in the long-term at a reduced dose, but side effects such as diabetes mellitus, hypertension, and duodenal ulcers were observed. Long-term steroid therapy is therefore the treatment of choice for the oral lesions of pemphigus vulgaris, but in some cases alternative treatment options may be required.

Adult↗
PubMed1991

Isotretinoin treatment alters steroid metabolism in women with acne.

The effect of isotretinoin (Roaccutane) on serum steroids and urinary steroid metabolites was investigated in seven female patients receiving the drug for treatment of severe acne over a 16-week period. Serum concentrations of dehydroepiandrosterone sulphate (DHAS), androstenedione (A2), and free androgen index (FAI) were not significantly altered. There was a significant fall in testosterone during treatment and a significant reduction in the 24 h urinary excretion of androsterone, tetrahydrocortisone (THE) and tetrahydrocortisol (THF) from week 8 onwards and for aetiocholanolone and allo-THF from week 12 (P less than 0.05). Although pretreatment levels of urinary steroid metabolites were not abnormal, the ratios of the 5 alpha/5 beta metabolites (androsterone:aetiocholanolone and allo-THF:THF) were at the upper limit of the reference range and were lowered after treatment, suggesting that 5 alpha-reductase activity is sensitive to isotretinoin.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1990

Psoriasis consultation audit: a two-centre study.

The adequacy of hospital note-keeping in 100 patients presenting with psoriasis at two teaching hospitals has been assessed. The criteria used were defined in consultation with a peer group of 60 British dermatologists. The pattern of record keeping was similar in both centres. Where differences existed between consultant (C) and non-consultant (J) staff, non-consultant staff completed the records more fully. There were differences between centres in the recording of patients' symptoms and disability, psoriasis type, and in the number of visits before discharge to general practitioners care. Both centres had a poor record of communication to general practitioners following patient default from the clinic. In both centres, the patient had only a one in 8 chance of subsequently being seen by a consultant if at the first visit they had been seen by a non-consultant. This simple case-note audit has highlighted the similarity of practice in the two centres and has resulted in practical improvements in record keeping.

Communication↗
PubMed1989

Acne in schoolchildren: no longer a concern for dermatologists.

OBJECTIVE: To determine the prevalence and severity of acne among schoolchildren in Glasgow. DESIGN: Secondary schools in Glasgow were divided by postcode into five socioeconomic cluster groups. Different numbers of schools were selected at random from the five groups to ensure proportional representation. One class from each registration year of the chosen schools was selected at random and the whole class recruited into the study. SETTING: 15 Secondary schools in Glasgow. SUBJECTS: 2014 Randomly selected schoolchildren aged 12-17 (5% of total secondary school roll). INTERVENTIONS: None. END POINT: Assessment of facial acne by two independent examiners by a recognised acne scoring system. MEASUREMENTS AND MAIN RESULTS: The prevalence of acne in boys increased from 40% (75/189) at age 12 to 95% (108/114) at age 16, and in girls it increased from 61% (114/187) at age 12 to 83% (136/164) at age 16. On a scale of 0 to 10 only 18 boys (1.8%) and three girls (0.3%) had grades of acne of 1.0 or greater; most of the pupils had grade 0.05-0.375 (minimal) acne. Nine per cent of boys (88/973) and 14% of girls (145/1041) had visited their general practitioner specifically for advice on and treatment for acne; only five pupils (0.3%) had been referred to a dermatologist. CONCLUSIONS: Both the prevalence and severity of acne have decreased over the past 20 years. This has probably been due to improvement of treatment for acne by primary care doctors and the greater availability and use of over the counter preparations for acne.

Acne Vulgaris↗
PubMed1989

Reduction of UV-induced erythema in normal subjects by applying methimazole.

Since free radicals are probably involved in the induction of erythema following ultraviolet (UV) irradiation, a study was conducted to investigate the influence of a topical application of methimazole (a free radical scavenger), before and at different times up to 2 h, after exposure to UV radiation. Seven subjects took part and erythema was assessed 6 h after exposure by a quantitative reflectance technique. Erythema was reduced at the sites that received methimazole 15 min prior to exposure and, although the trend was towards a decrease in erythema at the sites where methimazole was applied after exposure, the mean differences in these cases were not significant. It is believed that methimazole may have a useful role in the reduction of erythema following UV irradiation.

Administration, Cutaneous↗