Ultra Cryo-Milling with Liquid Nitrogen and Dry Ice Beads: Characterization of Dry Ice as Milling Beads for Application to Various Drug Compounds.

Ultra cryo-milling using liquid nitrogen (LN2) and dry ice beads has been proposed as a contamination-free milling technique. The morphological change of dry ice beads was visually monitored in LN2 to clarify their production process and cryo-milling process. We found that dry ice pellets, which are starting material of beads and available on the market, immediately disintegrate in LN2, resulting in the spontaneous production of dry ice beads. In addition, the resultant beads maintain their size and shape even under vigorous agitation in LN2, demonstrating that they could play a role of milling media in the milling process. The driving conditions of this cryogenic milling process including beads size were optimized to enhance the milling efficiency. Dry ice beads provided superior milling efficiency compared to original pellets. The milling efficiency increased as the size of the dry ice beads decreased; furthermore, the larger the amount of beads used, the finer the milled particles. Any crystals of three drug compounds were effectively pulverized to the sub- or single-micron range. Cryo-milling with dry ice beads is valuable on pharmaceutical field because it does not contaminate the product with fractured and/or eroded beads.

A case of refractory bullous pemphigoid with plasmapheresis-associated thrombopenia: efficacy of pulsed intravenous cyclophosphamide therapy.

We present a 69-year-old woman with refractory bullous pemphigoid successfully treated with pulsed intravenous cyclophosphamide therapy. Because various other early treatments including 4,4'-diaminodiphenylsulphone (DDS), minocycline/nicotinamide, cyclosporin, azathioprine, high-dose oral prednisolone, and methylprednisolone pulse therapy were either ineffective or intolerable, she was treated with double filtration plasmapheresis, but she responded poorly with the rare complication of severe transient thrombopenia. Finally, she gradually recovered with pulsed intravenous cyclophosphamide therapy.

Detection of various types of human papillomavirus DNA, mainly belonging to the cutaneous-group, more frequently in normal tissue than in squamous cell carcinomas of the lip.

BACKGROUND: Mucosal high-risk human papillomaviruses (HPVs), such as type 16, are detectable in oral cancers, especially of the oropharynx and tonsils, and there is evidence that they play a pathogenetic role in some cases. However, information is limited about their significance for cancers of the vermilion of the lip. OBJECTIVE: To determine the detection rate, types and localization of HPVs in squamous cell carcinomas (SCCs) of the lip. METHODS: Nested PCR for cutaneous HPVs, including epidermodysplasia verruciformis-related HPV (EV-HPV), and single PCR for mucosal HPVs, were conducted for a total of 27 SCCs and normal samples from 30 individuals. Tyramide-based in situ hybridization (ISH) was also applied. RESULTS: Various types of HPVs were detected, particularly from normal individuals. Among the kinds of the HPV types detected in this study, half were found by PCR using a primer pair, which we newly designed. The prevalence of HPV was 5 out of 27 SCCs (ca. 18%) and 10 out of 30 normal individuals (ca. 33%). They were the entire cutaneous-group except for two, from one SCC and one normal individual. CONCLUSION: On the surface of the normal lip various types of mainly cutaneous-group HPVs may be present, but there does not appear to be any obvious association with SCCs developing in this site.

The successful use of topical tacrolimus treatment for a chronic actinic dermatitis patient with complications of idiopathic leukopenia.

Chronic actinic dermatitis (CAD) is a photosensitivity disorder marked by severe eczematous lesions on exposed areas. Although associations with contact dermatitis, atopic dermatitis, and human immunodeficiency virus (HIV) have been suggested, its pathogenesis remains unknown. CAD is often refractory, and systemic administration of cyclosporin A has been the treatment of choice. Recently, topical tacrolimus therapy has been reported to be effective. We report the efficacy of topical tacrolimus treatment in a CAD patient who also had the complication of idiopathic leukopenia. A phototest showed marked suppression of erythema formation in the skin pre-treated with tacrolimus before UVB radiation but not in the skin treated after the irradiation. Therefore, it is suggested that tacrolimus may prevent UV-B induced erythema by suppressing a very early phase of the inflammatory process in CAD.

Squamous cell carcinoma of the anal margin with pruritus ani of long duration.

BACKGROUND: Anal margin is an unusual location for squamous cell carcinoma (SCC). On rare occasions, anal margin carcinoma is the cause of pruritus ani. OBJECTIVE: To describe a case of SCC of the anal margin with pruritus ani of long duration. RESULTS: A 52-year-old man had been aware of perianal itching for over 10 years. Examination of the perianal area revealed a reddish, eroded, hard nodule that was 2.0 x 1.5 x 0.3 cm in size located in the 3 o'clock position. The histopathologic diagnosis was well-differentiated SCC. The nodule was totally excised with a 1-cm margin. No recurrence or metastases were observed for 7 months. CONCLUSION: When pruritus ani does not respond to conservative therapy and when symptoms have existed for a long time, we should suspect the presence of malignancy.