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We present a case of so-called butcher’s warts in a meat handler with atopic dermatitis. PCR with direct sequence analysis confirmed the presence of HPV 7 in the hand warts of the patient. Histopathologically, the lesion contained vacuolated cells with centered nuclei, and there were no abundant keratohyalin granules in the granular layer. Clinically, HPV 7-induced warts tend to appear on the hands of meat/fish handlers or cutters in the world. Therefore, meat/fish had been thought to act as a vector for the transmission of HPV 7. In our case, the Japanese patient’s occupation required the handling of meat/fish products, and HPV 7 was found from his hand warts. This evidence indicated that HPV 7 was widely distributed in the world. However, this patient worked in a Japanese restaurant, which required the handling of meat/fish products with tools such as knives and chopping boards. Therefore, we suggested that HPV 7 might be correlated with specific reservoirs.

Kawasaki disease (KD) is vasculitis of unknown etiology in infants and young children. The diagnostic criteria for KD include major and minor symptoms, but various nail lesions are not described in detail. The aim of this study was to identify symptoms that are relatively found in nail of KD as diagnostic markers. After literature review, various nail lesions are classified as Beau's lines, leukonychia, onychomadesis, orange-brown chromonychia, and pincer nail deformity. The orange-brown chromonychia is the most common nail lesion in KD. In this study, the authors found three cases of KD with orange-brown chromonychia; two of these cases included rare dotted or splinter hemorrhages in the nail bed that were found on dermoscopic examination. The authors propose that these nail lesions, including hemorrhage of the nail bed, could be included as a helpful diagnosis of KD.

Trial design Human papillomavirus infection causes verruca vulgaris. CDK9 inhibitor FIT039 inhibits DNA virus proliferation in animal models. We conducted a multicenter, single-blind, placebo-controlled, randomized phase I/II clinical trial evaluating the safety and efficacy of FIT039 against verruca vulgaris. Methods Target lesions were treated with liquid nitrogen once, and a FIT039 patch or placebo patch was applied for 14 days. The primary endpoint was lesion disappearance. The secondary endpoints were safety and changes in dimension, cross-sectional area, and the number of petechial lesions. Results A total of 24 participants were randomly allocated to the FIT039 (n = 13, median age, 54 years) and placebo (n = 11, median age, 62 years) groups. Verruca vulgaris did not disappear. FIT039 decreased the dimension to 76% of the initial value on day 29, followed by an increase to 98% on day 57. Placebo showed a monotonic increase to 107% on day 57. Changes in the cross-sectional area and petechiae number were comparable between the groups. Conclusions No drug-related adverse reactions occurred. FIT039 efficacy was not determined in this study.

We herein present a case of annular basal cell carcinoma (BCC) with spontaneous regression on the right temporal region of a 56-year-old Japanese male. Histopathological examination revealed that the central section had no tumor cells. The sweat glands, follicles, and other cutaneous appendages were also absent. This pattern of spontaneous regression is quite uncommon, and understanding the histopathology may be important for future approaches to BCC.

Anogenital warts are caused by human papillomavirus types 6 and 11. They are rare in children, and treatment is difficult since conventional treatments are generally painful and require the patient to be anesthetized. Topical diphenylcyclopropenone (DPCP) is a contact immunotherapy used for treatments of recalcitrant warts and alopecia areata. We herein report 3 cases of anogenital warts in children successfully treated with topical DPCP. Our results suggest that topical DPCP may be a valuable option for the treatment of anogenital warts in children who have difficulty with painful destructive therapy.

There is no simple test to identify the human papillomavirus (HPV) genotypes that cause cutaneous warts. A new polymerase chain reaction (PCR) method, called SK-PCR, was developed for this purpose. This PCR amplifies 210-238 base pairs of L1 DNA of 17 HPV types (HPV-1a, -2a, -3, -4, -7, -10, -27, -28, -29, -40, -57, -60, -63, -65, -77, -91, and -94), which are thought to cause various cutaneous warts, including common, flat, butcher's, punctate, and pigmented warts. The method is novel because the location of these primers is completely different from that of any previous PCR method for HPV. The target sequences are specific to alpha-, gamma-, and mu-papillomaviruses (PVs), but not to beta-PVs. Furthermore, direct sequencing and restriction fragment length polymorphism (RFLP) were used to determine the HPV genotypes. Fifty of samples of plantar warts were examined, and HPV-27 was identified in 22 warts, HPV-57 in 15 warts, and HPV-2a in 9 warts. These PVs, which are alpha species 4, were the most common. HPV-4 and -65 (gamma-PVs) and HPV-1a and -63 (mu-PVs) were detected in one case each. A single HPV type was identified in all of these warts. This method appears to be useful for genotyping the HPVs causing skin warts, and for distinguishing between HPV-induced warts and warty lesions unrelated to HPV infection.

We have shown previously that PI3K/Akt pathway is active after cell differentiation in HL60 cells. In the present study, we have investigated whether additional molecules, such as protein kinase C (PKC), are involved in the regulation, not only of telomerase, but also of leukemia cell differentiation. We show that PKC activates telomerase and is, itself, activated following VD3- or ATRA-induced differentiation of HL60 cells, as was observed for PI3K/Akt. To clarify the significance of PI3K/Akt and PKC pathway activation in leukemia cell differentiation, we examined the active proteins in either the downstream or upstream regulation of these pathways. In conjunction with the activation of Akt or PKC, mTOR and S6K were phosphorylated and the protein expression levels of Rictor were increased, compared with Raptor, following cell differentiation. Silencing by Rictor siRNA resulted in the attenuation of Akt phosphorylation on Ser473 and PKCα/βII phosphorylation, as well as the inhibition of Rictor itself, suggesting that Rictor is an upstream regulator of both Akt and PKC. In addition, in cells induced to differentiate by ATRA or VD3, Nitroblue-tetrazolium (NBT) reduction and esterase activity, were blocked either by LY294002, a PI3K inhibitor, or by BIM, a PKC inhibitor, without affecting cell surface markers such as CD11b or CD14. Intriguingly, the silencing of Rictor by its siRNA also suppressed the reducing ability of NBT following VD3-induced cell differentiation. Taken together, our results show that Rictor associated with mTOR (mTORC2) regulates the activity of both Akt and PKC that are involved in cell functions such as NBT reduction and esterase activity induced by leukemia cell differentiation.

BACKGROUND Various laser therapies have been used to treat viral warts, and numerous successful results have been reported, but plantar warts are notoriously difficult to treat and eradicate. MATERIALS & METHODS This study included 35 lesions in 31 patients (17 female, 14 male) with plantar warts. We used a carbon dioxide (CO2) laser for incisions, and the defect was covered with artificial dermis. Follow-up periods ranged from 3 to 12 months. Overall, we examined the presence or absence of human papillomaviruses (HPVs) DNA in the lesional skin of all cases and at the excisional site after treatment in 20 cases. RESULTS Thirty-one of 35 lesions (88.6%) achieved complete clearance after one treatment session. We observed local recurrence in four lesions (11.4%). The application of salicylic acid was effective in treating minor recurrent cases. After complete remission, HPV DNA was not detected in the upper epidermis of the postoperative site. No significant scars or severe pain were seen in any patients. CONCLUSION A combination of CO2 laser therapy and artificial dermis application effectively treated the majority of plantar warts after one treatment, with complete and rapid clearance and no persistent pain. The authors have indicated no significant interest with commercial supporters.

Human papillomavirus type 7 (HPV-7) was originally identified in common warts of butchers. It has remained unclear, however, whether HPV-7 also induces other distinct types of cutaneous lesions. We observed similar keratoses on the groins of 2 patients. The lesions presented as multiple, smooth and small with little change in color from that of the adjacent skin and were diagnosed as condylomas. Their histological features were acanthosis, papillomatosis and parakeratosis with hyperkeratotic perinuclear vacuolation in the granular layer. By Southern blot analysis, HPV-7 DNA was identified in both condylomas. We conclude that HPV-7 infection causes condyloma. In addition, we discuss the long-held dogma regarding the association of HPV-7 with butcher’s warts and highlight the potential need for clinicians to know causal HPV types in cutaneous lesions given the increased use of prophylactic HPV vaccines.

We describe a case of systemic lupus erythematosus (SLE)-associated cutaneous cryptococcosis. A 32-year-old woman with SLE and lupus nephritis presented with the erythematous maculae on the chest and the extremities, in which encapsulated yeasts were revealed, and was diagnosed with secondary cutaneous cryptococcosis. We administered fluconazole (FLCZ) and then itraconazole (ITCZ) instead of amphotericin B (AMPH-B) to avoid the risk of renal toxicity of AMPH-B in the patient. While treatment with FLCZ was not particularly effective, repeated intermittent administration of ITCZ on a "3-day on/off cycle" (i.e. medication on 3 consecutive days and suspension for the next 3 days in turn) achieved complete remission of the cryptococcosis.

We examined the presence of human papillomavirus (HPV) DNA in tissues of premalignant skin lesions, i.e., actinic keratosis (n = 13) and Bowen's disease (n = 62), taken from 69 Japanese immunocompetent and renal transplant recipient patients. Detection and typing of HPV DNA were performed using polymerase chain reaction (PCR) and sequence analysis or restriction fragment length polymorphism (RFLP) analysis, respectively. The positivity rates of HPV DNA in tissues of actinic keratosis and Bowen's disease were 77% and 65%, respectively. Twenty-seven HPV types were detected in 50 (67%) premalignant skin lesions, in which Z95963 (accession no. in the EMBL Databank), Z95968, AJ010823, and AJ000151 have been described as partial sequences of unknown HPV types. Furthermore, 2 unknown types, HPVX1 and HPVX2, were found in specimens of actinic keratosis. Sequence analysis showed that HPVX1 is related to HPV-37 (86.1% sequence homology) and that HPVX2 is related to HPV-38 (79.7%). These results indicate that various mucosal and epidermodysplasia verruciformis-related HPV types are associated with the pathogenesis of actinic keratosis and Bowen's disease. In addition, 24 specimens of HPV-positive or HPV-negative premalignant skin lesions were examined immunohistochemically for proliferating cells to determine biological differences between HPV-positive and HPV-negative lesions. Immunohistochemistry for p21(Waf1/Cip1), p53, proliferating cell nuclear antigen (PCNA), Ki-67, and Bcl-2 revealed that there was no significant difference in the cell proliferation activity between HPV-positive and HPV-negative lesions, suggesting that HPV infection alone does not induce cell proliferation in those lesions.

A 69-year-old Japanese woman presented with multiple, erythematous, keratotic plaques distributed on her right breast, right shoulder, and left cubital fossa. The lesions varied in size from 5 mm to 6 cm. The patient had first noticed a small area of primary erythema on her left cubital fossa at the age of 18 years. The number and size of the lesions had increased for 50 years. A black nodule appeared on the plaque on the right breast 3 years ago and enlarged to 5 cm in diameter (Fig. 1A). Figure 1. (a) Erythematous plaques varying in size distributed on both breasts. The biggest plaque contained hyperkeratotic tumor. The black nodule appeared on the plaque of the right breast. (b) Six months after black tumor removal, hypertrophic change was noted on the scar. Topical application of vitamin D3 analog caused regression in size and elevation of the largest keratotic plaque, and a decrease in hyperkeratosis of the other eruptions Download figure to PowerPoint The patient was born to healthy nonconsanguineous parents. She grew up in the center of Kanazawa city, Ishikawa prefecture, central area of Japan, and had no history of arsenic exposure or outdoor work. She had no past history of repeated infectious diseases and no family history of recalcitrant warts. A tuberculin test gave an area of induration, 1.0 cm in diameter, in 48 h. The black tumor on the breast was surgically removed with a margin of uninvolved skin. Biopsies from lesions on the right breast (hyperkeratotic erythematous plaque) and left cubital fossa (small erythema without hyperkeratosis) were performed. Microscopic examination of hematoxylin and eosin-stained sections from all specimens showed similar findings. Nests of anaplastic keratinocytes were present in an intraepidermal epithelioma pattern within the expanded epidermal layer. A superficial dermal inflammatory cell infiltrate was also observed. There were irregular masses of epidermal cells that proliferated downwards into the dermis. Atypical mitotic figures, multinucleated keratinocytes, and individual cell keratinization were also observed (Fig. 2). Large clear keratinocytes, specific for epidermodysplasia verruciformis, were not found. Anti-papillomavirus antibody (Dako, Japan) did not react with any of the specimens. A histologic diagnosis of Bowen's disease (BD) (squamous cell carcinoma in situ) was made. Figure 2. In the biopsy specimen from the erythematous plaque on the breast, there were irregular masses of epidermal cells that showed atypical mitotic figures, multinucleation, and individual cell keratinization (hematoxylin and eosin stain, × 100) Download figure to PowerPoint Because the other lesions were distributed diffusely and the patient refused surgical treatment, oral etretinate (10 mg/day) was started; however, dryness of the lips and a burning sensation of the involved skin were intolerable. Therefore, topical application of 1-α,24-dihydroxyvitamin D3 ointment (tacalcitol, Bonalpha™) was chosen as alternative treatment. This vitamin D3 analog provided some relief to the redness and hyperkeratosis of all the erythematous plaques. Moreover, the largest keratotic plaque showed a remarkable regression in size and elevation 6 months later (Fig. 1B). No new tumors or erythematous plaques have been found for 3 years since vitamin D3 analog treatment started. DNA from two frozen tissue samples (black, smooth-surfaced tumor and hyperkeratotic erythematous plaque) was extracted by a standard proteinase K/phenol–chloroform–isoamyl alcohol extraction technique. Samples of total cellular DNA (100 ng) were amplified by polymerase chain reaction (PCR) using four sets of degenerate primers (F10/B5, F12/B5, CP66/CP69, and GP5/GP6) in the highly conserved region of the L1 open reading frame of papillomaviruses (Shamanin V, Delius H, de Villiers EM. Development of a broad spectrum PCR assay for papillomaviruses and its application in screening lung cancer biopsies. J Gen Virol 1994; 75: 1149–1156; Shamanin V, zur Hausen H, Lavergne D, et al. Human papillomavirus infections in nonmelanoma skin cancers from renal transplant recipients and nonimmunosuppressed patients. J Natl Cancer Inst 1996; 88: 802–811; de Villiers EM, Lavergne D, McLaren K, Benton EC. Prevailing papillomavirus types in non-melanoma carcinomas of the skin in renal allograft recipients. Int J Cancer 1997; 73: 356–361). For each set of reactions, negative controls for reagents and DNA were included and processed in the same way as the lesional samples throughout all PCR steps. Two human papillomavirus (HPV) plasmids (0.01 pg) containing the genotypes HPV-4 and HPV-6 served as positive controls. PCR products (10 µL) were subjected to 2% agarose gel electrophoresis. Three sets of primers (F10/B5, F12/B5, and CP66/CP69) amplified HPV-specific DNA fragments in both DNA samples from the BD lesion (Fig. 3). The recombinant plasmids harboring the insert of the amplified DNA were sequenced. The sequences obtained were compared with the available HPV sequences in GenBank (National Center for Biotechnology Information, National Institutes of Health), using the husar software package (Deutsches Krebsforschungszentrum). The sequences of all plasmids corresponded to the L1 portion of HPV-5, except for a few nucleotide substitutions. Figure 3. Results of polymerase chain reaction: 650-bp bands appear in lanes 1, 3, and 4 (human papillomavirus, HPV). Larger sized bands are nonspecific products (NS). Lane M, size marker. Lane 1, DNA extracted from HPV-6 (positive control). Lane 2, DNA extracted from human placenta. Lane 3, DNA extracted from black tumor. Lane 4, DNA extracted from hyperkeratotic plaque Download figure to PowerPoint

We reported the case of a 92-year-old woman with a pigmented and non-pigmented surface of the pedunculated nodule on her lower leg. Microscopic examination revealed that this nodule consisted of a component of small, dark, homogenous, poroid cells and cuticular cells in the dermis. The histopathological features of the lesion were consistent with poroid neoplasm. Immunohistochemistry showed that HMB-45 and Melan-A were positive in malanocytes and melanophages of the pigmented areas. Unlike most poroid neoplasms, this case showed pigmented lesion mimicked nodular melanoma.

We describe a case of an 82-year-old Japanese woman with basal cell carcinoma (BCC) on the leg with secondary chronic lymphedema due to treatment for uterine cancer. Sparse tumor nests with remarkable edema of the dermis in the nodule appeared to be influenced by the chronic lymphedema. However, it remains inconclusive whether or not the tumorigenesis of the BCC was associated with chronic lymphedema in this case.

We describe a 62-year-old Japanese woman who had skin lesions involving her extremities, chest and back that showed spontaneous remission. The skin lesions consisted of slightly atrophic scars and crusted, reddish or necrotic papules. A tuberculin test showed induration and bulla, which was regarded as strongly positivity. Histopathologically, a tuberculoid granuloma with necrosis was present in the upper dermis and the deep dermis, including the adipose tissues. Bacterial cultures were not positive from sputum, urine or stool, and the chest X-P was also normal. After skin biopsy, all the lesions disappeared within 1 month. No relapse was noted in the entire body.

We used two imatinib resistant cell lines, K562-ADM cells, which over-express P-glycoprotein (a product of the ABCB1 gene, more commonly known as MDR1), and K562-hTERT cells, which over-express the telomerase reverse transcriptase (TERT), as models to show that the acquisition of multidrug resistance in CML is associated with the enhanced phosphorylation of signal transducer and activator of transcription 5 (STAT5). The induction of P-glycoprotein expression that occurred in response to adriamycin treatment was accompanied by increased phosphorylation of BCR-ABL and STAT5, as well as increased telomerase protein expression. Intriguingly, a ChIP assay using an anti-STAT5 antibody revealed direct binding of STAT5 to the promoter regions of both the human TERT gene and the MDR1 gene in K562-ADM cells. Conversely, silencing of endogenous STAT5 expression by siRNA significantly reduced both the expression of P-glycoprotein and telomerase activity and resulted in the recovery of the imatinib sensitivity of K562-ADM cells. These findings indicate a critical role for STAT5 in the induction of P-glycoprotein and in the modulation of telomerase activity in drug-resistant CML cells. Furthermore, primary leukemic cells obtained from patients in blast crisis showed increased levels of phospho-STAT5, P-glycoprotein and telomerase. In contrast, none of these proteins were detectable in the cells obtained from patients in the chronic phase. Together, these findings indicate a novel mechanism that contributes toward multidrug resistance involving STAT5 as a sensor for cytotoxic drugs in CML patients.

Background Specific substance of Maruyama (SSM) is a carcinostatic immunotherapeutic agent extracted from Mycobacterium tuberculosis . The efficacy of SSM induced interleukin(IL)-12 and IFN-γ production, and inhibition of IL-4, resulting in a shift from Th2 to Th1 in vivo. Objective The DS- Nh mice are a model of human atopic dermatitis (AD), which spontaneously develop dermatitis under conventional conditions. In this study, to determine whether SSM can prevent the development of skin lesions in a murine model of AD. Methods DS- Nh mice were injected with SSM 5 days per week for 11 weeks. Pharmacological, histological and serological studies were performed to investigate the therapeutic effect of SSM for DS- Nh mice. Analysis of cytokines responses to SSM using quantitative RT-PCR and flow cytometry were also performed to evaluate their therapeutic mechanisms in these AD model mice. Results Clinically, erythema, erosions, excoriation, and edema were observed in DS- Nh mice at 16 weeks of age, which advanced with age. Histologically, the relative number of mast cells increased in DS- Nh mice. SSM treatment alleviated the clinical and histological findings in accord with reduced serum IgE level, and increased IgG2a level. TSLP expression was not induced, but IL-1β, IL-12, IL-17A, and IFN-γ were induced in SSM-treated DS- Nh mice. Overall, SSM treatments increased the number of activated DCs in lesions. SSM induced CD80, CD86, and MHC class II expression on bone marrow-derived DCs. Conclusions SSM enhanced IL-12 production, but suppressed TSLP expression, resulting in a shift from Th2 to Th1 responses. This shift suppressed AD-like skin lesions in a similar fashion as the BCG vaccine. Therefore, SSM may be a useful adjuvant for suppressing skin lesions in AD models.

Background The clinical course of human papillomavirus (HPV) associated with Bowenoid papulosis and condyloma acuminatum of anogenital tumors are still unknown. Here we evaluated molecules that are relevant to cellular proliferation and regulation of apoptosis in HPV associated anogenital tumors. Methods We investigated the levels of telomerase activity, and inhibitor of apoptosis proteins (IAPs) family (c-IAP1, c-IAP2, XIAP) and c-Myc mRNA expression levels in 20 specimens of Bowenoid papulosis and 36 specimens of condyloma acuminatum in anogenital areas. Overall, phosphorylated (p-) AKT, p-ribosomal protein S6 (S6) and p-4E-binding protein 1 (4EBP1) expression levels were examined by immunohistochemistry in anogenital tumors both with and without positive telomerase activity. Results Positive telomerase activity was detected in 41.7% of Bowenoid papulosis and 27.3% of condyloma acuminatum compared to normal skin (p < 0.001). In contrast, the expression levels of Bowenoid papulosis indicated that c-IAP1, c-IAP2 and XIAP mRNA were significantly upregulated compared to those in both condyloma acuminatum samples (p < 0.001, p < 0.001, p = 0.022, respectively) and normal skin (p < 0.001, p = 0.002, p = 0.034, respectively). Overall, 30% of Bowenoid papulosis with high risk HPV strongly promoted IAPs family and c-Myc but condyloma acuminatum did not significantly activate those genes. Immunohistochemically, p-Akt and p-S6 expressions were associated with positive telomerase activity but not with p-4EBP1 expression. Conclusion Combined analysis of the IAPs family, c-Myc mRNA expression, telomerase activity levels and p-Akt/p-S6 expressions may provide clinically relevant molecular markers in HPV associated anogenital tumors.

We describe a case of malignant melanoma on the ungual region of the index finger with which 6 sentinel lymph nodes were detected in the axillary basin. Of these nodes, 1 of 3 brachial nodes and 2 of 3 central axillary nodes showed micrometastasis. Additional lymph nodes obtained at the subsequent complete axillary lymph node dissection showed no metastasis. Identification of as many as 6 sentinel lymph nodes was ascribed to a single lymph trunk that would branch off to afferent lymphatics draining to each nodal group; however, a gamma probe may have detected radioactive tracer passing to the sequential nodes as well as that remaining in true sentinel nodes.

We investigated the level of telomerase activity (TA) in 17 specimens of non-genital Bowen's disease (BD) and in 14 specimens of skin without sun exposure (non-exposed skin) using a non-isotopic PCR-based telomeric repeat amplification protocol (TRAP) assay. Expression of human telomerase reverse transcriptase (hTERT; the catalytic subunit of telomerase) was also evaluated by immunochemistry in the non-genital BD tissues. Moderate to high levels of TA were detected in 41.2% of 17 non-genital BD specimens (P = 0.001). In contrast, TA was not evident in non-exposed skin. Recently, nucleolin was reported to be associated with hTERT, so we used this antibody instead of hTERT antibody. Immunohistochemistry showed that nucleolin expression was associated with high TA levels in non-genital BD. Our results also revealed differences of TA levels among non-genital BD specimens. High levels of TA in those specimens were not age related. Five out of 7 specimens (71.4%) with moderate to high TA levels were from sun-exposed sites, while the remaining 10 specimens with low levels of TA were from non-exposed sites. These results suggested that cellular DNA damage caused by ultraviolet irradiation might be associated with an increase of TA in non-genital BD. Among non-genital BD specimens, 4 out of 17 (23.5%) showed high levels of TA (median relative TA value: 79.8%; P = 0.003), which might be associated with immortalization or transformation to invasive squamous cell carcinoma.

We describe an 81-year-old Japanese woman who had a palm-sized, erythematous plaque with a nodular lesion on the lateral abdomen. The biopsy specimens taken from the erythematous plaque and reddish nodule show that bowenoid changes were present in the epidermis and epidermis to dermis, respectively. A sentinel lymph node biopsy (SNB) was performed with blue dye and radioisotope in her right groin region and two lymph nodes were found to be occupied by many atypical cells. The erythematous plaque with nodular lesion was completely removed with a 3-cm margin under general anesthesia, and complete regional lymph node dissection was also performed. In addition, high telomerase activity was seen in the erythema plaque while using a telomeric repeat amplification protocol assay. In conclusion, some instances of Bowen's disease might have high telomerase activity in the atypical cells and can progress to Bowen's carcinoma. The SNB was regarded as a useful method to detect early lymph node metastases in this case.

Summary Background Infraorbital dark circles and wrinkles of the lower eyelids are a cosmetic problem, especially with age. Aims To determine whether a gel containing 2% phytonadione, 0.1% retinol and 0.1% vitamins C and E is effective in reducing dark under-eye circles and wrinkles of the lower eyelids in healthy Japanese adults. Patients/Methods Fifty-seven adult Japanese volunteers with dark under-eye circles and wrinkles were enrolled in an open label study. The gel formulation was applied twice daily to the lower eyelid site for 8 weeks. Haemostasis, pigmentation and wrinkles were evaluated by a physician and by the patients themselves, using a digital camera and a visual analogue scale respectively, after 4 and 8 weeks of treatment. Results Topical application of the gel decreased not only haemostasis but also wrinkles after 8 weeks of treatment. Of 57 patients, 27 (47%) had reductions in haemostasis. Wrinkles were also decreased in some patients. However, pigmentation was not clearly removed by this gel. Conclusions Topical application of the gel containing 2% phytonadione, 0.1% retinol, 0.1% vitamin C and 0.1% vitamin E was fairly or moderately effective in reducing dark under-eye circles, especially in cases of haemostasis, over a short treatment period in healthy Japanese adults. This treatment also slightly decreased wrinkles.

Cimetidine has been shown to improve various types of human neoplasms and more recently it has been shown to be effective in treating recalcitrant or multiple viral warts in some reports. However, it is not well understood why cimetidine is effective on those kinds of viral warts. We investigated 55 patients with multiple viral warts treated only with oral cimetidine for up to 4 months to examine the efficacy of treatment. The patients were divided into two groups: group A received oral cimetidine (20 mg/kg/day) and group B received the drug (30 to 40 mg/kg/day). In addition, using real time PCR, we measured mRNA levels of the cytokines interleukin-2 (IL-2), IL-18, and interferon (IFN)-gamma taken from selected punch biopsy specimens before and during treatment. As a result, 34.5% (19/55) of the patients had a dramatic clinical improvement or complete remission (CR) of their viral warts and 23.6% (13/55) of the patients had partial responses (PR) within 4 months of cimetidine therapy. IL-2 and IFN-gamma mRNA levels were significantly increased and IL-18 mRNA levels were decreased in tissues of effectively treated viral warts. Our results show that the higher dose of oral cimetidine was more effective in treating multiple viral warts, that cimetidine activates Th1 cells to produce IL-2 and IFN-c and that their expression correlates with wart remission. These results suggest that cimetidine is an effective treatment for viral warts. In addition, based on the decrease in IL-18 mRNA elicited by the drug, IL-18 might be expressed by keratinocytes infected with HPV.

We describe herein a case of multiple Bowen's disease that developed on the left hand fingers of an 80-year-old male patient who had practiced as a gynecologist. PCR-based analysis indicated that the lesion contained human papillomavirus (HPV) type 18 DNA. Topical application of bleomycin and liquid nitrogen cryotherapy were effective in treating this case. After treatment, histopathologically no atypical cells were seen throughout the epidermis.