Andrew G Smith

University Hospital Of North Staffordshire NHS Trust, Stoke-upon-Trent, England, United Kingdom

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Publications (17)106.52 Total impact

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    ABSTRACT: The skin biopsy is considered one of the most important tools in dermatology. Two primary reasons a clinician may perform a skin biopsy are either to establish a diagnosis or to evaluate therapy. The objective of this study was to critically assess the value of the skin biopsy as a diagnostic test for inflammatory dermatoses. One hundred consecutive skin biopsy specimens where an inflammatory dermatosis was queried were reviewed. To assess the diagnostic ability of the skin biopsy, the frequency with which a correct diagnosis was made based on histopathological analysis alone was recorded, that is, an initial "blind" diagnosis made without clinical data. Once this was recorded, the clinical history was provided and a posthistory diagnosis reached. The posthistory diagnosis was then compared with the final working diagnosis in the patient case notes. In 55% of cases, histology was able to provide a prehistory specific diagnosis. In 31% of cases, histology was not able to provide a specific diagnosis but could provide a differential diagnosis. In two thirds of these (20 of the 31 cases), the diagnosis was reached posthistory with clinicopathologic correlation. In 12% of cases, histology could only provide a pattern analysis, and in 2% of cases, only a descriptive report could be issued. In 13% of cases, the biopsy provided the final working diagnosis, which had not been considered clinically. The skin biopsy for inflammatory dermatoses is clearly a worthwhile investigative procedure. Prehistory blind histology based on microscopic data provided an accurate diagnosis correlating to the working diagnosis in 53% of cases. The diagnostic boundaries of dermatopathology are such that in an additional 25 cases (25%) a diagnosis was reached with aid of clinical data proving the importance of providing a well-thought-out differential diagnosis. Overall, in 78% of cases, histology with the aid of clinical information was able to provide an accurate diagnosis correlating to the working diagnosis.
    The American Journal of dermatopathology 07/2009; 31(4):350-3. · 1.30 Impact Factor
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    ABSTRACT: The rate of development of further basal cell carcinoma (BCC) after first presentation is highly variable. The mechanisms that determine this phenotypic difference are unclear. We assessed the risks of developing a subsequent BCC in patients who developed a BCC and a squamous cell carcinoma (SCC) and compared them with patients who developed a BCC only. In all, 1040 patients who developed BCC only were compared with 140 patients who developed BCC and SCC to see whether the latter group included a high proportion of risk phenotypes (eg, male sex and fair skin). We then compared the number of BCCs developing per year in the two groups (174 BCC only and 71 BCC/SCC) during a 5-year period after initial BCC presentation. The BCC/SCC group demonstrated a significantly lower BCC/year rate than BCC only group. The rate of development of further BCC during 5-year follow-up was lower in the BCC/SCC group because a smaller number of patients developed subsequent BCC and not because the same proportion of patients developed lesions but in smaller numbers. After 5 years of follow-up, 51.1% of BCC and 74.6% of BCC/SCC cases were free from a subsequent BCC. Logistic regression analysis corrected for age at initial presentation confirmed that patients with BCC/SCC were less likely to develop a further BCC during the 5 years after initial presentation (P = .001, odds ratio = 0.31, 95% confidence interval 0.15-0.63). Because of the large patient group and long study follow-up from the date of the index BCC or SCC, not all data were obtained. Where this is the case, the number of patients for whom the information is available is provided. Patients who develop a BCC are similar to patients who develop both a BCC and SCC, confirming the overlap of causative factors. Patients who develop both a BCC and SCC are less likely to develop BCCs compared with patients who develop BCC only.
    Journal of the American Academy of Dermatology 06/2009; 61(2):247-51. · 4.91 Impact Factor
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    ABSTRACT: Nonmelanoma skin cancer (NMSC) causes significant morbidity and mortality posttransplantation. We examined the annual incidence of NMSC in U.K. renal transplant recipients (RTRs). A total of 269 (95% of potential population) RTRs of skin type I-IV were recruited into a prospective study of NMSC incidence between 1998 and 2006. A total of 244 (91% enrolled) RTRs were screened on at least one occasion. The mean incidence per year of NMSC was 7.82% (SD: 1.84), comprising a mean (SD) incidence per year of squamous cell carcinoma 3.45% (1.36), basal cell carcinoma 3.58% (1.17), and Bowen's disease 2.52% (0.91). The risk of developing NMSC increased with duration posttransplantation: the mean incidence per year of NMSC was 3.27% (0.53) in RTRs <5 years posttransplantation, 5.86% (3.1) in RTRs 5-10 years posttransplant, and 11.1% (1.85) in those >10 years posttransplant. Relatively low NMSC incidence rates within the first 5 years posttransplantation suggests that duration posttransplantation may determine the optimum frequency of surveillance of RTRs in the United Kingdom.
    Transplantation 08/2007; 84(3):437-9. · 3.78 Impact Factor
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    ABSTRACT: One previous study has shown a higher prevalence of sebaceous hyperplasia (SH) in patients with heart transplant on immunosuppressive drugs as compared with sex-matched control patients. We set out to compare the prevalence of SH in a cohort of patients undergoing renal transplant with age- and sex-matched control patients and to find any association with nonmelanoma skin cancer (NMSC) in these patients. In all, 117 patients with renal transplant and 117 age- and sex-matched control patients were screened for the prevalence of SH and NMSC. We found that 29.9% of our patients with renal transplant had SH; 16 of 35 (45.7%) of these patients had a history of NMSC as compared with 6 of 82 (7.3%) patients without SH (P < .001, odds ratio 10.7). In the age- and sex-matched control group, a total of 28 patients (23.9%) had one or more lesions of SH. This study is small and will require confirmation with larger cohort studies. In our cohort of patients with renal transplant we found a strong association of NMSC with SH. This association remained significant after correction of factors such as age, sex, skin type, and duration of transplant.
    Journal of the American Academy of Dermatology 12/2006; 55(5):878-81. · 4.91 Impact Factor
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    ABSTRACT: Cutaneous basal cell carcinoma (BCC) risk is mediated by interactions between ultraviolet radiation (UVR) and host factors, including DNA repair efficiency. We investigated the association between BCC risk and SNPs in exon 6 (c.466C > A, dbSNP238406:g.C > A; designated C/A156), exon 10 (c.932G > A, dbSNP1799793:g.G > A; designated G/A312), and exon 23 (c.2251A > C, dbSNP13181:g.A > C; designated A/C751) of the nucleotide excision repair gene, XPD (ERCC2; excision repair cross-complementing repair deficiency, complementation 2 [xeroderma pigmentosum D]). XPD genotype frequencies were not significantly different in 509 cases and 379 controls, although AA156 (odds ratio [OR]=0.61, 95% confidence interval [CI]=0.37-1.01, P=0.052) and AA312 (OR=0.65, 95% CI=0.40-1.05, P=0.08) were linked with reduced risk. A156-A312 and A156-A312-A751 haplotype frequencies however, were significantly lower in cases than controls (OR=0.12, 95% CI=0.05-0.31, P < 0.001; OR=0.10, 95% CI=0.03-0.33, P < 0.001). We confirmed the robustness of these findings by showing significant associations of the haplotypes with risk in two randomly selected equal sized groups of cases and controls and, using the false positive report probability (FPRP) approach (FPRP values < 0.001 and < 0.004, respectively). A156-A312 was similarly associated with reduced risk in subgroups, including cases with no family history of skin cancer, with only BCC on the head/neck, and those with a high rate of increase in BCC numbers. The association was not dependent on gender, age, or extent of UVR exposure. A156-A312 was found in 6.3% of controls and the corresponding risk haplotype, C156-G312 (OR=1.65, 95% CI=1.21-2.26, P=0.002) in 35.4% of controls. We interpret these data as showing that XPD SNP mediate susceptibility to BCC.
    Human Mutation 04/2005; 25(4):353-9. · 5.21 Impact Factor
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    ABSTRACT: Patients with basal cell carcinoma (BCC) frequently develop further tumors during follow-up. We sought to elucidate the relative effects of pattern of ultraviolet radiation exposure, and site and histologic type of the first tumor, on the rate of increase in BCC numbers. We used negative binomial regression analysis to study the association of selected variables on the rate of increase in BCC numbers in 266 Caucasian patients who first presented with a tumor on the head/neck or trunk with nodular or superficial histology. Patients with an initial truncal BCC with superficial histology demonstrated significantly faster increases in BCC numbers than did patients with other site and histology combinations. These data indicate that site and histology define subsets of patients with BCC.
    Journal of the American Academy of Dermatology 04/2005; 52(3 Pt 1):468-73. · 4.91 Impact Factor
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    ABSTRACT: While sunlight is critical in basal cell carcinoma (BCC) pathogenesis the relationship between exposure and tumor site and histology is unclear. We determined if tumor site (trunk or head/neck) or histology (nodular or superficial) is determined by exposure pattern. In 66 cases with truncal and 362 patients with head/neck BCC at first presentation, average hours exposure/year, intermittency score, childhood sunburning and skin type were not significantly associated with tumor site or histology. However, often sunbathing was associated with a five-fold increased risk of truncal BCC. Average sunbathing score was significantly greater in 22 cases with truncal compared with 325 cases with head/neck nodular tumors and also in 44 cases with superficial truncal compared with superficial head/neck BCC. Thus, sunbathing determined tumor site but not histology.
    Cancer Letters 01/2005; 216(2):191-7. · 5.02 Impact Factor
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    ABSTRACT: After first presentation with a basal cell carcinoma (BCC), patients demonstrate interindividual diversity in the rate of development of further BCCs (number/year of follow-up). The mechanism for this variation is unknown. In this study, we evaluated whether PTCH variants mediate this phenomenon. We used negative binomial regression analysis to identify associations between BCC numbers/year and host characteristics, parameters of exposure to ultraviolet radiation (UVR), and PTCH exon 12(1686) C/T, intron 15(2560+9) G/C, and exon 23(3944) C/T genotypes and haplotypes in 279 BCC cases who presented with an initial tumor on the head/neck. PTCH genotypes were not significantly associated with BCCs/year, although cases with two copies of the C1686-C3944 haplotype developed significantly fewer BCCs/year than those without this haplotype (rate ratio = 0.44; 95% CI = 0.27-0.71). Cases with one copy of T1686-T3944 developed more BCCs/year (rate ratio = 2.46; 95% CI = 1.27-3.97) than those without the haplotype. We found no significant associations between BCCs/year and the other PTCH haplotypes studied. We reexamined the association of C1686-C3944 with BCCs/year in a model that included UVR exposure parameters (sunburning in childhood, sunbathing score, intermittency of exposure between 40 and 60 years of age, exposure in hours/year) and skin type, gender, and age at first presentation. The association between C1686-C3944 and BCCs/year remained significant (rate ratio = 0.44; 95% CI = 0.26-0.73 for two copies of the haplotype). The data show that allelic variation in PTCH contributes to the rate of development of BCC.
    Environmental and Molecular Mutagenesis 02/2004; 44(5):469-76. · 3.71 Impact Factor
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    ABSTRACT: Caucasian renal transplant recipients living in Queensland, Australia, have the highest risk of nonmelanoma skin cancer in the world. To determine clinical and environmental factors associated with posttransplantation nonmelanoma skin cancer in Queensland. 361 Caucasian adult recipients completed a structured interview and full skin examination. Skin cancer details were obtained from hospital records. Squamous cell carcinoma was strongly associated with blue or hazel eyes, time resident in a hot climate, and pretransplantation squamous cell carcinoma; tumor numbers were associated with birth in a hot climate, childhood sunburn, pretransplantation actinic keratoses, and smoking. The risk of basal cell carcinoma was strongly associated with acute or intermittent sun exposure during childhood and pretransplantation basal cell carcinoma; numbers were associated with blue or hazel eyes, time spent living in a hot climate, and male gender. Clinical and environmental factors can be used to identify recipients at risk of nonmelanoma skin cancer in Queensland.
    Journal of the American Academy of Dermatology 10/2003; 49(3):397-406. · 4.91 Impact Factor
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    ABSTRACT: Patients with a basal cell carcinomas (BCC) have an increased risk of further tumors. We studied the individual and combined impact of gender, skin type and allelic genes cytochrome P450 (CYP2D6), vitamin D receptor (VDR), tumor necrosis factor-alpha, TNF-alpha) on the rate of increase in BCC numbers after first presentation. Individually, male gender, skin type 1, CYP2D6 EM, VDR TT and TNF-alpha GG were associated with more BCC/year (rate ratio (RR) 1.20-1.36) while RR for associations of combinations of two, three and four variables were greater than in their reference categories (RR 1.32-1.90, 2.20-2.84, 3.06-5.49, respectively). The data show that different factors mediate the numbers of BCC/year in males and females and, the individual contributions of variables to risk is modest.
    Cancer Letters 02/2003; 189(2):175-81. · 5.02 Impact Factor
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    ABSTRACT: Renal transplant recipients are at high risk for multiple non-melanoma skin cancers (NMSC) that occur at a younger age and behave more aggressively. Consequently, the American Society of Transplantation has recommended that physicians conduct annual screenings for NMSC in this population. Few centres currently offer a dedicated surveillance programme. This article discusses a model for skin cancer surveillance in which a trained nurse works within a validated competency programme to provide annual skin surveillance and education in the renal transplant outpatient clinic.
    Nephrology nursing journal: journal of the American Nephrology Nurses' Association 07/2002; 29(3):257-9, 267.
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    ABSTRACT: Malignant melanoma, the most serious cutaneous malignancy, has attracted substantial attention because of its rapidly increasing incidence and the poor prognosis of some tumours. Little is known of the genetic factors that mediate susceptibility to, and outcome of, sporadic malignant melanoma. Because of its role in mitogenesis, which is especially relevant to wound healing, tumorigenesis, and proliferation of epidermal tissues, epidermal growth factor (EGF) is an attractive candidate in which to look for genetic polymorphisms. We enrolled 135 white European patients with malignant melanoma and 99 healthy white European controls, and screened a selection of DNA samples for polymorphisms in the promoter and 5' untranslated region of the EGF gene by analysis. We then screened DNA samples from all participants for the identified polymorphism by restriction-fragment-length polymorphism (RFLP) analysis. In-vitro EGF production was measured in peripheral-blood mononuclear cells from 34 controls, and the results were compared with the individuals' EGF genotypes. We identified a single nucleotide substitution (G to A) at position 61 of the EGF gene. Allele frequencies in the controls were 56% EGF 61*A and 44% EGF 61*G. Cells from individuals homozygous for the 61*A allele produced significantly less EGF than cells from 61*G homozygotes (p=0.0004) or heterozygous A/G individuals (p=0.001). Compared with the A/A genotype, G/G was significantly associated with Breslow thickness (p=0.045) and with risk of malignant melanoma (odds ratio 4.9 [95% CI 2.3-10.2], p<0.0001). This study suggests that high EGF production might be important in the development of malignant melanoma.
    The Lancet 03/2002; 359(9304):397-401. · 39.06 Impact Factor
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    ABSTRACT: BACKGROUND Basal cell carcinoma (BCC) is characterized by marked interpatient variation in tumor accrual. The authors previously reported that presentation with a cluster of BCC is associated with an inherited predisposition to develop many additional lesions suggesting clustering is a critical event. A cluster is defined as the presence of two or more new, primary BCCs, at initial or later presentation.METHODS The authors recruited 927 cases and determined whether 1) clustering was an early or late event and 2) tumor accrual was altered after clustering.RESULTSIn the cases, 669 patients developed only 1 lesion, 112 patients presented more than once but with single lesions (single presentation phenotype[SPP]-more), 94 cases had a cluster at first presentation (multiple presentation phenotype [MPP]-cluster initial), and 52 cases first presented with 1 lesion but later had a cluster (MPP-cluster later). The authors found that 1) clustering occurred relatively late. The mean ages at first presentation with 1 BCC of the SPP-more (61.5 years) and MPP-cluster later patients (60.4 years) were similar although presentations with clusters in the MPP-cluster initial (67.6 years, P = 0.0002) and -cluster later cases (68.1 years, P = 0.002) occurred significantly later. 2) Clustering was associated with increased accrual. Thus, 26 patients (MPP-cluster later/a) in the MPP-cluster later group had a additional BCC postcluster. Mean accrual post-cluster (1.99 BCC/year) in these cases was significantly increased (P = 0.0001) compared with precluster accrual (0.39 BCC/year).CONCLUSIONS The authors found that the formation of BCC clusters represents a critical event such that after a cluster presentation, tumor accrual is significantly increased. Cluster presentation is a relatively late event suggesting reduced effectiveness in immune surveillance. Cancer 2000;89:1012–8. © 2000 American Cancer Society.
    Cancer 08/2000; 89(5):1012 - 1018. · 5.20 Impact Factor
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    ABSTRACT: We previously described associations between basal cell carcinoma (BCC) numbers and allelic variants at loci that mediate host response to ultraviolet radiation (UV). These associations were largely exerted in cases with the multiple presentation phenotype (MPP). This phenotype describes patients who present at their first or a later presentation with a cluster of BCC (2-10 new BCC). Remaining BCC cases have the single presentation phenotype (SPP) and may develop more than one BCC but only have single new lesions at any presentation. We proposed that the MPP cases comprise a high-risk group as they suffer significantly more lesions than SPP cases. We are attempting to determine, in the total BCC case group and subgroups, how many genes influence BCC numbers and their relative importance. In this study, we assessed the influence of two further candidates, glutathione S-transferase GSTP1 and cyclin D1 (CCND1), on tumour numbers in a total group of 457 patients comprising MPP and SPP cases. The relative importance of these genes in comparison with occupational UV exposure and host response (skin type) was also considered. We found that the frequencies of GSTP1 genotypes based on the Ile105 and Val105-expressing alleles and CCND1 AA, AG, GG genotypes were similar in MPP and SPP cases and that there were no significant associations between GSTP1 or CCND1 genotypes and BCC numbers in the total or SPP groups. However, in the MPP cases, GSTP1 Val105/Val105 was associated with more tumours (P = 0.05, reference GSTP1 Ile105/Ile105). Inclusion of skin type and indoor/outdoor occupation in the negative binomial regression models did not alter the associations of these genotypes with tumour numbers. DNA from 258 cases was analysed to identify GSTP1*A (Ile105-Ala114), GSTP1*B (Val105-Ala114), GSTP1*C (Val105-Val114) and GSTP1*D (Ile105-Val114). In SPP cases, there was no association between BCC numbers and GSTP1 BB, though the association with GSTP1 BC approached significance (P = 0.09). In MPP cases, GSTP1 BC was associated with BCC numbers (P = 0.03). We also found that the interaction term, GSTP1 Val105/Val105 with CCND1 AA, was associated with BCC numbers in the total (P = 0.001) and MPP (P = 0.006) but not SPP (P = 0.68) groups. In a stepwise model including GSTP1 Val105/Val105, CCND1 AA and their interaction terms as well as GSTM1, GSTT1 and CYP2D6 genotypes, skin type 1 and gender, the combination of genotypes was the best predictor of BCC numbers. These data suggest that study of further genes involved in cell-cycle control and protection from oxidative stress will be useful, particularly in high-risk subgroups.
    Pharmacogenetics and Genomics 07/2000; 10(6):545-556. · 3.61 Impact Factor
  • Cancer 01/2000; 89(5):1012-1018. · 5.20 Impact Factor
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    ABSTRACT: We previously identified associations between polymorphism in the cytochrome P450 CYP2D6 gene and outcome in several cancers. We have now examined the hypothesis that homozygosity for the mutant alleles, CYP2D6*4 and CYP2D6*3, is associated with susceptibility and outcome in malignant melanoma. Outcome was assessed by Breslow thickness. We first confirmed previous reports that these mutant alleles are associated with increased susceptibility to malignant melanoma. For example, the frequency of homozygosity for CYP2D6*4 was significantly greater (P = 0.006, chi-squared 1 d.f. = 7.4, odds ratio 2.2, 95% confidence interval 1.2, 3.9) in cases (9.1%) than in control individuals (4.3%). The frequency of homozygosity for the mutant alleles was next examined in the malignant melanoma cases grouped on the basis of characteristics associated with malignant melanoma risk. Homozygosity was significantly more common (P = 0.038) in cases with red/blonde hair than in those with brown/black hair. We found no associations between the CYP2D6 genotype and sex, skin type or eye colour. The possible association of CYP2D6 with outcome was assessed by comparing genotype frequencies in patients with tumours of Breslow thickness < 1.5 mm with those whose tumours were >= 1.5 mm. In patients with red/blonde, but not brown or black hair, homozygosity for CYP2D6*4 was significantly associated with thicker lesions in a multivariate model (P = 0.036). We further examined the association of CYP2D6*4 homozygosity with red/blonde hair by classifying patients on the basis of homo- or heterozygosity for wild-type or va192met, asp294his or asp84glu melanocyte stimulating hormone receptor (MC1R) alleles. None of the nine patients with brown/black hair with the asp294his allele were homozygotes for CYP2D6*4. By contrast, in the patients with red/blonde hair, three of five cases with asp294his were homozygotes for the mutant CYP2D6 allele. The difference in the frequency of CYP2D6*4 homozygotes in the red/blonde cases with wild-type MC1R alleles compared with those with asp294his was significant (exact P = 0.029). No associations between val92his or asp84glu and CYP2D6 alleles were identified. (C) 1999 Lippincott Williams & Wilkins, Inc.
    Pharmacogenetics and Genomics 05/1999; 9(3). · 3.61 Impact Factor
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    ABSTRACT: Allelic variation at the melanocyte stimulating hormone receptor (MC1R) gene has been linked with sun-sensitive skin types, suggesting it is a susceptibility candidate for melanoma. We determined the frequency of the val92met, asp294his, and asp84glu MC1R alleles in 190 Caucasian controls and 306 melanoma cases and studied their association with skin type and hair color. The percentage of controls with at least one val92met, asp294his, or asp84glu allele was 17.3%, 6.8%, and 3.5%, respectively. Individually, frequencies of the val92met, asp294his, or asp84glu alleles in the controls with skin types 3 and 4 were similar to those with skin types 1 and 2. Trend analysis, however, did identify an association (exact p = 0.048, two-sided test) between skin type and MC1R variants in the group comprising all controls with any one or more of these alleles. There was no association between MC1R alleles and hair color. Allele frequencies were not different in melanoma cases and controls. There were no associations between skin types and the proportion of cases with the asp294his or asp84glu alleles, though the association between skin type and the val92met allele approached significance (exact p = 0.09, two-sided test). Unexpectedly, in the group comprising all cases with one or more variant alleles, the proportion of subjects with variant alleles increased with skin types associated with tanning rather than burning, although trend analysis showed that this association did not quite reach statistical significance (exact p = 0.08, two-sided test). Asp84glu (but not val92met or asp294his) variant alleles were more common in subjects with blonde hair, although the relationship between the asp84glu allele and hair color did not achieve statistical significance (23 = 6.16, exact p = 0.10). We interpret the data presented as indicating that polymorphism at MC1R does not appear a major determinant of skin type, at least in terms of these allelic variants. Furthermore, considered alone, these alleles are not susceptibility candidates for malignant melanoma.Keywords: genetic predisposition, ultraviolet light
    Journal of Investigative Dermatology 07/1998; 111(2):218-221. · 6.19 Impact Factor

Publication Stats

359 Citations
106.52 Total Impact Points


  • 1998–2005
    • University Hospital Of North Staffordshire NHS Trust
      • Department of Dermatology
      Stoke-upon-Trent, England, United Kingdom
    • Keele University
      • Institute for Science and Technology in Medicine
      Newcastle-under-Lyme, England, United Kingdom
  • 2002–2003
    • Staffordshire and Stoke-On-Trent Partnership NHS Trust
      Newcastle-under-Lyme, England, United Kingdom