African Americans (AAs) have a 1.5 times higher risk of colorectal carcinoma (CRC) than Caucasians. Gene silencing through CpG island hypermethylation has been associated with the genesis or progression of microsatellite instability (MSI) largely due to 1 target for hypermethylation being the DNA mismatch repair gene hMLH1; there is anecdotal evidence of an increased incidence of MSI among AAs. P16 and hMLH1 can be inactivated by hypermethylation of their respective promoter regions, abrogating the ability to regulate cell proliferation and repair processes. We studied such methylation, as well as hMHS2 expression in colorectal cancers from AA patients to determine if MSI is associated with epigenetic silencing. Experiments were conducted on matched normal and colon cancer tissues from AA patients (n = 51). A total of 5 microsatellite markers (D2S123, D5S346, D17S250, BAT25 and BAT26) were used to evaluate MSI status. P16 and hMLH1 promoter methylation status was determined following bisulfite modification of DNA and using methylation specific PCR, while immunohistochemistry (IHC) was used to examine expression of hMLH1 and hMSH2. A total of 22 (43%) cancers demonstrated microsatellite instability‐high (MSI‐H), while 27 were microsatellite stable (MSS) and 2 were microsatellite instability‐low (MSH‐L). Most of the MSI‐H tumors were proximal, well differentiated and highly mucinous. Most patients in the MSI‐H group were females (68%). The p16 promoter was methylated in 19 of 47 (40%) tumors. A total of 7 of these CRCs demonstrated MSI‐H (33%). The hMLH1 promoter was methylated in 29 of 34 (85%) tumors, of which 13 CRCs demonstrated MSI‐H (87%). hMLH1 and hMSH2 staining was observed in 66% and 38% of MSI‐H tumors, respectively. Overall, the prevalence of MSI‐H colorectal tumor was 2‐3‐fold higher, while the defect in the percentage expression of mismatch repair (MMR) genes (hMLH1 and hMSH2) was similar in AA patients compared to the U.S. Caucasian population. Similar numbers of AA MSS tumors with p16 and hMLH1 methylation likely indicate hemimethylation of genes that might reflect environmental or genetic influences that might be more common in the AA population. © 2005 Wiley‐Liss, Inc.

myeloablative conditioning regimen and 80% of the patients in the RIC group. In the myeloablative group (n ϭ 79), 39 patients (49%) received the combination of cyclophosphamide plus TBI, 18 patients (23%) received busulfan plus cyclophosphamide, and 22 patients (28%) received other chemotherapy-containing protocols. In the RIC group (n ϭ 89), the vast majority of the patients received allograft with fludarabine-containing regimens: fludarabine plus melphalan, 30 patients (33%); fludarabine plus cyclophosphamide, 23 patients (26%); fludarabine plus busulfan, 12 patients (13%); and other combinations, nine patients (10%). Only seven patients (8%) received lowdose TBI in the conditioning regimen. Although the number of patients treated with low-dose TBI was low, all of them experienced relapse after transplantation and died as a result of disease progression. Intensity of conditioning regimen seems to be important, taking into account the heavily pretreated and sometimes refractory population of patients who are included in allogeneic protocols, as has been indicated by others. 5

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Isotretinoin was temporarily discontinued when the patient required high-dose oral prednisolone for an exacerbation of his UC. Within 1 month of stopping oral corticosteroids, the PG relapsed with the development of new painful sterile pustules. Isotretinoin was reinstated (0AE25 mg kg )1 daily) with dramatic and sustained resolution and without recourse to oral steroids to date. Treatment has been well tolerated for the past 4 years with no derangement of serum liver enzymes or fasting lipids and no exacerbations of his underlying UC.Since its first description in the 1930s, the aetiology of PG has remained an enigma. About 50% of cases are associated with underlying systemic diseases such as inflammatory bowel disease, rheumatoid arthritis and haematological malignancies. 1 PG is often challenging to manage and usually requires aggressive local and systemic treatment. No guidelines for treatment of PG have been established thus far. Corticosteroids or ciclosporin are now considered first-line systemic agents. In steroid-refractory PG associated with inflammatory bowel disease, immunomodulatory therapy and biological response modifiers are promising new therapies. 2 In the case described, recalcitrant superficial PG was successfully treated with isotretinoin therapy and no complications were observed. A review of the literature revealed one similar case, where PG in association with acne conglobata and seronegative spondyloarthropathy cleared following 4 weeks of treatment with isotretinoin (0AE75 mg kg )1 daily). 3 Isotretinoin (13-cis-retinoic acid) is widely recognized for its use in the management of nodulocystic acne and in recent years it has been shown useful in the management of a number of chronic recalcitrant dermatoses. 4 Isotretinoin has been reported to interfere with neutrophil function and has been shown in vitro to inhibit neutrophil release of inflammatory mediators. 5 PG is regarded as part of the spectrum of the neutrophilic dermatoses, reactive processes that have dermal neutrophilia in common. Although the pathogenesis of PG is poorly understood, neutrophil hyper-reactivity has been suggested. 6 We postulate that isotretinoin may be effective in the treatment of PG by virtue of its inhibitory effect on neutrophil function and we suggest that low-dose isotretinoin be considered as a potential therapeutic option for recalcitrant PG.