J M McGregor

Mandeville Regional Hospital, Мандевиль, Manchester, Jamaica

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Publications (97)446.75 Total impact

  • European journal of dermatology : EJD. 02/2014;
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    ABSTRACT: Ultraviolet radiation (UV) B is a substantial risk factor for skin cancer in both the immune competent and immunosuppressed organ transplant population (OTR). In OTRs, additional exposure to UVA through drug photosensitisation may contribute to their excess risk, which is well established. (1) There is some evidence for preferential lateralisation of photodamage and (pre)-cancers, in the general population, to the side most exposed to UVR whilst driving. Moehrle et al reported that left-sided drivers receive 5 times more UV to the left arm than the right arm, and 20 times more UV on the left side of the face than the right (2). Actinic keratoses have been reported to occur more frequently on the right side of the body in Australian drivers, where drivers sit on the right side of the car. A left sided bias in skin cancer was observed in the United States where drivers sit on the left side of the car (3, 4, 5). This article is protected by copyright. All rights reserved.
    British Journal of Dermatology 04/2013; · 3.76 Impact Factor
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    ABSTRACT: Skin cancer is a frequent complication of organ transplantation. Current guidelines advise specialist skin surveillance but there are limited data on how these should be implemented. This study determines overall burden of cancer and relevant intervals for strategic surveillance in an ethnically diverse transplant population. Prospective data on time to first and subsequent cancers and cumulative burden with respect to defined risk factors were analyzed in a cohort of 1010 patients in a UK center over 22 years. Among 931 individuals transplanted >6 months (mean 10.3 years), 1820 skin cancers occurred in 267 (29%) individuals and were multiple in 66%. Cumulative incidence at 5, 10, 20 and 30 years was 11%, 25%, 54% and 74%, with median time to second, third and fourth cancers of 24, 14.7 and 8.4 months, respectively. Tumors were overwhelmingly squamous and basal cell carcinomas (73% and 24%, respectively). Skin phototype, ultraviolet radiation exposure, age at transplant and duration of transplant were significant risk predictors and were used to construct clinically relevant surveillance intervals. This study provides a comprehensive, prospective analysis of skin cancer morbidity and risk in an ethnically diverse transplant population from which we derive an evidence-based skin cancer surveillance program.
    American Journal of Transplantation 10/2012; · 6.19 Impact Factor
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    ABSTRACT: An increased frequency of renal carcinoma in men with melanoma has been reported in population based-studies. We report the clinicopathological findings of five cases of synchronous renal cell carcinoma (RCC), identified after routine radiological staging for cutaneous malignant melanoma (MM) between October 2006 and October 2008. The five patients (three men and two women, with a mean age of 62.4 years), presented with six melanomas of varying subtypes. The mean Breslow thickness was 1.87 mm. There was no family history of cancer in any of the cases. Routine radiological staging identified a mass arising from the left kidney in three cases and the right kidney in two cases. All patients underwent radical nephrectomy, and histology in each case confirmed RCC of the clear-cell subtype. Mean follow-up was 3 years. Although the simultaneous occurrence of RCC and MM may be coincidental, there are several plausible aetiological links. Further analysis of the synchronous occurrence of MM and renal cancer may provide therapeutic insights into these two important tumours.
    Clinical and Experimental Dermatology 06/2012; · 1.33 Impact Factor
  • American Journal of Clinical Dermatology 02/2012; 13(1):64-5. · 2.52 Impact Factor
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    ABSTRACT: Azathioprine is associated with enhanced skin photosensitivity to ultraviolet A (UVA) and leads to incorporation of 6-thioguanine (6-TG) into DNA of dividing cells. Unlike canonical DNA, 6-TG DNA is damaged by UVA, which comprises more than 90% of the ultraviolet reaching earth. Skin photosensitivity to UVA and UVB was measured in 48 kidney transplant patients immunosuppressed either by azathioprine (n = 32) or mycophenolate (n = 16). In 23 patients, azathioprine was subsequently replaced by mycophenolate and skin photosensitivity, DNA 6-TG content in peripheral blood mononuclear cells, and susceptibility to UVA-induced DNA damage were monitored for up to 2 years. The mean minimal erythema dose to UVA on azathioprine was twofold lower than on mycophenolate. Three months after replacing azathioprine by mycophenolate mofetil, the minimal erythema dose to UVA had increased from 15 to 25 J/cm(2) (p < 0.001) accompanied by reduced DNA 6-TG content. P53 protein expression in irradiated skin indicated reduced susceptibility to UVA-induced DNA damage. 6-TG DNA in peripheral blood mononuclear cells remained measurable for over 2 years. Replacing azathioprine selectively reduced the skin photosensitivity to UVA, attenuated UVA-induced skin DNA damage, and is likely based on incorporated 6-TG in DNA.
    American Journal of Transplantation 09/2011; 12(1):218-25. · 6.19 Impact Factor
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    ABSTRACT: Organ transplant recipients (OTRs) have an increased risk of skin cancer. Treatment with azathioprine, commonly used in post-transplant immunosuppressive regimens, results in incorporation of 6-thioguanine (6-TG) into DNA. Mismatch repair (MMR)-defective cells are resistant to killing by 6-TG. Azathioprine exposure confers a survival advantage on MMR-defective cells, which are hypermutable and may therefore contribute to azathioprine-related nonmelanoma skin cancer, a phenomenon we have previously demonstrated in transplant-associated sebaceous carcinomas. The MSH2 protein is an important component of DNA MMR. The -6 exon 13 T>C MSH2 polymorphism is associated with impaired MMR, drug resistance and certain cancers. To investigate (i) whether loss of MMR protein expression and microsatellite instability are over-represented in squamous cell carcinomas (SCCs) from OTRs on azathioprine compared with SCCs from immunocompetent patients, and (ii) whether the MSH2 -6 exon 13 polymorphism is over-represented in OTRs with skin cancer on azathioprine. (i) Immunohistochemical staining was used to assess expression of the MMR proteins MSH2 and MLH1 in cutaneous SCCs from OTRs on azathioprine and from immunocompetent patients. (ii) Blood samples from OTRs on azathioprine with and without skin cancer were genotyped for the -6 exon 13 MSH2 polymorphism. (i) MSH2 and MLH1 protein expression was not altered in SCCs from OTRs on azathioprine and there was no difference in expression between SCCs from OTRs and immunocompetent patients. (ii) There was no association between MSH2 polymorphism genotype frequency and OTR skin cancer status. Despite previous findings in transplant-associated sebaceous carcinomas, defective MMR and the -6 exon 13 MSH2 polymorphism are unlikely to play a significant role in the development of SCC in OTRs on azathioprine.
    British Journal of Dermatology 10/2009; 162(4):732-42. · 3.76 Impact Factor
  • American Journal of Transplantation 05/2009; 9(4):862. · 6.19 Impact Factor
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    ABSTRACT: Before 1985, azathioprine and corticosteroids were used to suppress the immune response and prevent allograft rejection in organ transplant recipients. Since 1985, the majority of patients have received cyclosporin in combination with azathoprine and/or corticosteroids. More recently, other immunosuppressive agents have been introduced, including tacrolimus, sirolimus, and mycophenolate mofetil [1-3], which are described elsewhere in this book (see Part I).
    Cancer treatment and research 02/2009; 146:123-32.
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    ABSTRACT: The immunosuppressant azathioprine is used to prevent graft rejection after organ transplantation. To investigate whether azathioprine-associated mutagenesis contributes to the high incidence of skin tumours in organ transplant recipients (OTRs), we analysed PTCH gene mutations in 60 basal cell carcinomas (BCC); 39 from OTRs receiving azathioprine and 21 from individuals never exposed to azathioprine. PTCH was mutated in 55% of all tumours, independent of azathioprine treatment. In both the azathioprine and non-azathioprine groups, transitions at dipyrimidine sequences, considered to indicate mutation by ultraviolet-B radiation, occurred frequently in tumours from chronically sun-exposed skin. In BCC from non-sun-exposed skin of azathioprine-treated patients, there was an over-representation of unusual G:C to A:T transitions at non-dipyrimidine sites. These were exclusive to the azathioprine-exposed group and all in the same TGTC sequence context at different positions within PTCH. Meta-analysis of 247 BCCs from published studies indicated that these mutations are rare in sporadic BCC and had never previously been reported in this specific sequence context. This study of post-transplant BCC provides the first indication that azathioprine exposure may be associated with PTCH mutations, particularly in tumours from non-sun-exposed skin.
    British Journal of Cancer 11/2008; 99(8):1276-84. · 5.08 Impact Factor
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    ABSTRACT: Organ transplant recipients have a higher incidence of melanoma compared to the general population but the prognosis of this potentially fatal skin cancer in this group of patients has not yet been established. To address this, we undertook a multicenter retrospective analysis to assess outcome for 100 melanomas (91 posttransplant and 9 pretransplant) in 95 individuals. Data were collected in 14 specialist transplant dermatology clinics across Europe belonging to the Skin Care in Organ Transplant Patients, Europe (SCOPE) Network, and compared with age, sex, tumor thickness and ulceration status-matched controls from the American Joint Committee on Cancer (AJCC) melanoma database. Outcome for posttransplant melanoma was similar to that of the general population for T1 and T2 tumors (< or = 2 mm thickness); but was significantly worse for T3 and T4 tumors (> 2 mm thickness); all nine individuals with a pretransplant melanoma survived without disease recurrence following organ transplantation. These data have implications for both cutaneous surveillance in organ transplant recipients and management of transplant-associated melanoma.
    American Journal of Transplantation 09/2008; 8(9):1891-900. · 6.19 Impact Factor
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    ABSTRACT: Human papillomaviruses (HPVs) of the beta genus (beta-PV), especially HPV5 and HPV36, are proposed to play a pathogenic role in psoriasis, but many previous studies have failed to control for potential confounders, including treatment. To re-examine the relationship between beta-PV and psoriasis addressing limitations present in previous studies and analyse intra-patient concordance for carriage of HPV. Plucked eyebrow hairs and forearm skin scrapes were collected from 20 newly diagnosed, previously untreated adult patients with psoriasis and 23 normal controls. A combination of type-specific and degenerate polymerase chain reaction methods was used to achieve comprehensive HPV DNA detection. The prevalence of HPV in hair and skin from psoriasis patients was higher than in controls (83.3% vs. 46.7%, respectively, P < 0.03 corrected for age and clustering). HPV5 or HPV36 were not over-represented. The profile of diverse beta-PV types was comparable in the two groups. Intra-patient concordance for HPV DNA at separate sites was high (P < 0.00001). Our data do not support a specific causal role for HPV5 or HPV36 in psoriasis, but suggest that psoriatic skin may be more permissive for viral presence than normal skin. High intra-patient concordance for specific HPV types at separate sites, together with the ubiquity of HPV DNA in normal human skin, suggests that an individual becomes colonized with a particular beta-PV profile presumably to the exclusion of other types. To what extent this HPV profile is then causal in the subsequent development of hyperproliferative skin disease is unknown.
    British Journal of Dermatology 08/2008; 159(1):113-9. · 3.76 Impact Factor
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    ABSTRACT: Azathioprine is used to treat a variety of conditions and to prevent graft rejection in organ transplant recipients (OTRs). To investigate clinically our previous finding that azathioprine metabolites interact with ultraviolet (UV) A radiation to form promutagenic oxidative DNA damage and to determine whether this may be causal or contributory to the development of excess skin cancers post-transplantation. The clinical corollary of these data were investigated. Five patients were recruited and the minimal erythema dose (MED) for UVB, UVA and solar-simulated radiation (SSR) was determined for each person before, and at least 12 weeks after, starting azathioprine therapy. In all five patients azathioprine treatment was associated with an increased UVA and SSR sensitivity of the skin and a significant reduction in MEDs for UVA and SSR. We found no change in UVB-induced erythema or MED. In addition, we found that DNA from the skin of patients on azathioprine contains 6-thioguanine (6-TG). Our findings confirm the presence of DNA 6-TG in the skin of those taking therapeutic doses of azathioprine and provide support for the hypothesis that DNA damage occurs when DNA 6-TG interacts with UVA, resulting in abnormal cutaneous photosensitivity.
    British Journal of Dermatology 08/2008; 159(1):198-204. · 3.76 Impact Factor
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    ABSTRACT: Organ transplant recipients (OTR) are at high risk of developing nonmelanoma skin cancer and premalignant epidermal dysplasia (carcinoma in situ/ Bowen's disease and actinic keratoses). Epidermal dysplasia is often widespread and there are few comparative studies of available treatments. To compare topical methylaminolaevulinate (MAL) photodynamic therapy (PDT) with topical 5% fluorouracil (5-FU) cream in the treatment of post-transplant epidermal dysplasia. Eight OTRs with epidermal dysplasia were recruited to an open-label, single-centre, randomized, intrapatient comparative study. Treatment with two cycles of topical MAL PDT 1 week apart was randomly assigned to one area of epidermal dysplasia, and 5-FU cream was applied twice daily for 3 weeks to a clinically and histologically comparable area. Patients were reviewed at 1, 3 and 6 months after treatment. The main outcome measures were complete resolution rate (CRR), overall reduction in lesional area, treatment-associated pain and erythema, cosmetic outcome and global patient preference. At all time points evaluated after completion of treatment, PDT was more effective than 5-FU in achieving complete resolution: eight of nine lesional areas cleared with PDT (CRR 89%, 95% CI: 0.52-0.99), compared with one of nine lesional areas treated with 5-FU (CRR 11%, 95% CI: 0.003-0.48) (P = 0.02). The mean lesional area reduction was also proportionately greater with PDT than with 5-FU (100% vs. 79% respectively). Cosmetic outcome and patient preference were also superior in the PDT-treated group. Compared with topical 5-FU, MAL PDT was a more effective and cosmetically acceptable treatment for epidermal dysplasia in OTRs and was preferred by patients. Further studies are now required to confirm these results and to examine the effect of treating epidermal dysplasia with PDT on subsequent development of squamous cell carcinoma in this high risk population.
    British Journal of Dermatology 03/2007; 156(2):320-8. · 3.76 Impact Factor
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    ABSTRACT: Summaryp53 gene mutation appears to play an important role in the development of systemic lymphoma, and may be associated with tumour progression. Its role in cutaneous lymphoma is currently unknown. We examined p53 expression in 55 biopsies of cutaneous lymphoma, including patch-, plaque- and tumour-stage mycosis fungoides (MF), T- and B-cell lymphoma and lymphomatoid papulosis. Strong, homogeneous p53 expression, thought to correlate most closely with p53 gene mutation, was seen in only three cases; in a plaque and tumour from a patiënt with tumour-stage MF, in plaque-stage MF in a patient without tumours, and in one case of CD30+ large-cell anaplasüc lymphoma. These data suggest that p53 gene mutation is not a critical step in the development of the majority of primary cutaneous lymphomas.
    British Journal of Dermatology 07/2006; 132(3):353 - 358. · 3.76 Impact Factor
  • Archives of Dermatology 07/2006; 142(6):781-2. · 4.79 Impact Factor
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    ABSTRACT: Non-melanoma skin cancers (NMSCs) are increased in organ transplant recipients, but transplant and immunocompetent squamous and basal cell carcinomas (SCCs, BCCs) have not been compared previously in a single-center study. To compare clinicopathologic features of transplant and immunocompetent NMSCs. Consecutive transplant NMSCs (60 SCCs, 100 BCCs) and immunocompetent NMSCs (40 SCCs, 125 BCCs) presenting between 1995-1997. Transplant patients were 15 years younger at time of NMSC diagnosis compared with immunocompetent individuals, and transplant tumors were often more multiple and extracephalic. Spindle cell morphology was more common in transplant SCCs, a superficial component was more common in transplant BCCs, and histologic features of HPV infection were overrepresented in transplant tumors. Outcome was worse for transplant SCCs but not transplant BCCs. Histologic features required to identify HPV infection have not been validated. These findings have direct implications for clinical care. The increased frequency and distribution of transplant NMSCs underscore the importance of whole-body surveillance. Transplant SCCs, particularly those with diffuse spindle cell change, may require more aggressive management, whereas transplant BCCs do not. Finally, our data support differences in the pathogenesis of transplant NMSC, which may influence future preventive and therapeutic strategies.
    Journal of the American Academy of Dermatology 03/2006; 54(2):290-300. · 4.91 Impact Factor
  • Clinical and Experimental Dermatology 02/2006; 31(1):146-7. · 1.33 Impact Factor
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    ABSTRACT: Oxidative stress and mutagenic DNA lesions formed by reactive oxygen species (ROS) are linked to human malignancy. Clinical treatments inducing chronic oxidative stress may therefore carry a risk of therapy-related cancer. We suggest that immunosuppression by azathioprine (Aza) may be one such treatment. Aza causes the accumulation of 6-thioguanine (6-TG) in patients' DNA. Here we demonstrate that biologically relevant doses of ultraviolet A (UVA) generate ROS in cultured cells with 6-TG-substituted DNA and that 6-TG and UVA are synergistically mutagenic. A replication-blocking DNA 6-TG photoproduct, guanine sulfonate, was bypassed by error-prone, Y-family DNA polymerases in vitro. A preliminary analysis revealed that in five of five cases, Aza treatment was associated with a selective UVA photosensitivity. These findings may partly explain the prevalence of skin cancer in long-term survivors of organ transplantation.
    Science 10/2005; 309(5742):1871-4. · 31.20 Impact Factor
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    ABSTRACT: We describe two patients with a diagnosis of actinic prurigo who subsequently developed cutaneous B-cell lymphoma. This is the first report, to our knowledge, of this association. We propose that chronic antigenic stimulation by ultraviolet radiation, in the context of actinic prurigo, may have been causal in the development of these unusual lymphomas.
    British Journal of Dermatology 08/2005; 153(1):186-9. · 3.76 Impact Factor

Publication Stats

3k Citations
446.75 Total Impact Points

Institutions

  • 2012
    • Mandeville Regional Hospital
      Мандевиль, Manchester, Jamaica
  • 2005–2011
    • Queen Mary, University of London
      • Centre for Cutaneous Research
      London, ENG, United Kingdom
  • 2005–2008
    • University of London
      • The London School of Medicine and Dentistry
      Londinium, England, United Kingdom
  • 2001
    • St. John's Hospital
      Springfield, Illinois, United States
  • 2000–2001
    • King's College London
      • • St John's Institute of Dermatology
      • • Department of Twin Research and Genetic Epidemiology
      London, ENG, United Kingdom
    • The Kings College
      Brooklyn, New York, United States
    • Beaumont Hospital
      Dublin, Leinster, Ireland
  • 1998–2000
    • Royal Cornwall Hospitals NHS Trust
      Truro, England, United Kingdom
  • 1995
    • North Middlesex University Hospital NHS Trust
      Londinium, England, United Kingdom