[Interchangeability of resin composites and bonding agents based on bis-GMA or UDMA].

Recently, dentin bonding systems have been released separately from the resin composites, because the adhesive systems have been quickly improved. Since the merit of each material should be effectively utilized for each clinical case, the bonding systems and resin composites produced by different manufacturers may be combined according to the clinical purpose. The current restorative resins are basically categorized into two groups according to the main resin monomer, bis-GMA or UDMA resins. The purpose of this study was to evaluate the interchangeability between the bonding systems and resin composites, which were made by different manufacturers. Two bonding systems and five resin composites based on bis-GMA or UDMA were used in this study. The evaluation was performed by the tensile bond strength, fracture modes, and SEM observation, using the dentin surface of freshly-extracted bovine teeth. The highest bond strength (19.2 MPa) was shown by the combination of LBII sigma and AP-X. The bond strengths of nine other combinations were not statistically different (p > 0.05). There were many cohesive failures in dentin or resin composite, using all combinations. From the results, it was concluded that the interchangeability of the resin composites and bonding systems should be clinically acceptable.

Gold dermatitis due to ear piercing: correlations between gold and mercury hypersensitivities.

A case of allergic contact dermatitis due to gold pierced earrings is reported. The patient developed recurring redness and swelling on her earlobes a month after the wearing of pierced-type gold earrings, which was followed by the appearance of reddish nodules around the puncture marks. Patch tests revealed positive reactions to 0.1% mercuric chloride, 1% gold sodium thiomalate and 0.2% chloroauric acid. We also demonstrated that guinea pigs contact-sensitized with a mercuric compound developed positive patch test reactions to both mercuric and gold compounds. These results suggest that there may be correlations between gold and mercury hypersensitivities.

Allergenicity and tolerogenicity of amlexanox in the guinea pig.

Amlexanox (AMLX), an anti-allergic agent, is available in Japan as Elics opthalmic solution, Solfa nasal douche and Solfa tablets. Cases of allergic contact dermatitis induced by Elics ophthalmic solution, which contains 0.25% AMLX, were reported within a year of its introduction. We therefore examined the contact sensitizing potency of AMLX. Guinea pigs sensitized to 0.25% AMLX exhibited a strong positive patch test reaction. Further, AMLX-sensitized animals developed rashes following oral and systemic challenge with AMLX. This animal model reflected the clinical experience of systemic contact dermatitis due to AMLX. The non-responsiveness induced by oral administration of AMLX to AMLX-induced animals was transient, and clinical prophylaxis by desensitization with oral AMLX may only increase the risk of systemic contact dermatitis. On the other hand, there have been few reports of drug eruption from oral Solfa tablets in spite of their wide use. Therefore, we also examined the induction of tolerance by oral administration of AMLX. Oral administration of AMLX before sensitization resulted in complete non-responsiveness. It seems likely that a substantial reduction in the risk of AMLX sensitization by Elics may be achieved by prior oral administration of Solfa tablets containing AMLX.

Immunohistochemical study of graft-versus-host reaction (GVHR)-type drug eruptions.

Skin biopsies of graft-versus-host reaction (GVHR)-type drug eruptions in the acute phase were compared immunohistochemically with those in the chronic phase and also with non-GVHR type drug eruptions in the acute phase. Predominance of CD8+ T cells in the epidermal infiltrates, reduction in the number of epidermal OKT6+ dendritic cells (Langerhans cells), and increased expression of HLA-DR and ICAM-1 on keratinocytes were observed in the acute phase of GVHR-type, but not in either the chronic phase of GVHR-type or the acute non-GVHR type. These findings were similar to those of previous reports on skin lesions of acute GVH disease (GVHD) seen after bone marrow transplantation. Therefore, immunohistochemistry is not useful for differential diagnosis between acute GVHR-type drug eruptions and acute cutaneous GVHD. These findings also indicate that similar immunomechanisms may be involved in the pathogenesis of both GVHR-type drug eruptions and cutaneous GVHD.

Piroxicam has at least two epitopes for contact photoallergy.

We have demonstrated previously in guinea pigs that the induction of photocontact sensitivity to piroxicam (PXM) also induces a state of cross-reactive contact hypersensitivity to two compounds having structurally related elements, thimerosal (TMS) and thiosalicylate (TOS). The present study was conducted to determine whether oral administration of TOS would desensitize guinea pigs previously photosensitized with PXM. At the same time, the spectrum of reactivities against these compounds and against tenoxicam (TXM) which resembles only piroxicam was assessed by appropriate sensitizing and eliciting protocols. As expected, animals photosensitized to PXM developed reactivities against all four compounds, PXM and TXM (photosensitivity) and TMS and TOS (contact sensitivity). By contrast, photosensitization with TXM induced cross-reactivity only against PXM. Moreover, the induction of contact sensitivity against TMS or TOS induced photosensitive cross-reactivity to PXM, but not to TXM. Finally, the oral administration of TOS produced a transient desensitization only for TMS and TOS. These results suggest that photosensitization with PXM induces two distinct reactivities. The first reactivity cross-reacts with TMS and TOS and is suppressible with orally administered TOS. The second cross-reacts only with TXM and is not suppressible with oral TOS. We conclude that PXM acquires at least two distinct immunogenic epitopes when exposed to UVA irradiation.

A cross-reaction between piroxicam-photosensitivity and thiosalicylate hypersensitivity in lymphocyte proliferation test.

We examined the cross-reaction between photosensitivity to piroxicam (PXM) and contact sensitivity to thiosalicylate (TOS) by a lymphocyte proliferation test (LPT) in guinea pigs. The lymph node cells (LNCs) plus peritoneal exudate cells (PECs) from guinea pigs contact-sensitized with TOS remarkably cross-proliferated to PXM under UVA (4 J/cm2) irradiation. On the other hand, the PXM-photosensitized LNCs+PECs also cross-proliferated to TOS. From these results, the reciprocal cross-reaction between TOS-hypersensitivity and PXM-photosensitivity was reconfirmed by the in vitro LPT, indirectly indicating that the PXM-photosensitivity is a cell (probably T cell)-mediated PXM photoallergy in its nature. The TOS-primed LNCs+PECs did not cross-proliferate to UVA (4 J, 180 J or 500 J/cm2)-pretreated PXM (UVA-PXM) although it is supposed to contain several photoproducts of PXM. Furthermore, the TOS-primed LNCs developed a remarkable proliferative cross-response to the PECs pulsed with PXM under UVA (4 J/cm2) irradiation (photo-PXM-modified PECs), but not to the PECs pulsed with PXM or UVA-PXM. Therefore, it is presumed that the cross-reactive molecule, which is easily formed from PXM under UVA irradiation, is unstable, and that the formation of complete antigen by the generation of this molecule and its photobinding needs the coexistence of PECs, PXM and UVA irradiation at the same time in the culture.

Photosensitivity to piroxicam is induced by sensitization to thimerosal and thiosalicylate.

Piroxicam (PXM), a nonsteroidal anti-inflammatory drug, has been well known to often induce photosensitive eruptions within a few days after its administration. It has been reported that this photosensitivity correlates well with a positive patch-test reaction to thimerosal (TMS) and also to thiosalicylate (TOS), which is an active hapten of TMS. But it has not yet been concluded whether this correlation is caused by a cross-reaction among the drugs or not. In our experiments, animals contact-sensitized with TMS or TOS developed positive photopatch-test reactions to PXM, and those photocontact-sensitized with PXM had positive patch-test reactions to TMS and TOS. Photosensitive reactions were also induced by UVA irradiation (photo test) performed 90 min after perioral administration of PXM in the animals contact-sensitized with TMS or TOS. Analysis of the UVA-treated PXM by nuclear magnetic resonance spectrography and thin-layer chromatography revealed that the high dose of UVA induced photodecomposition of PXM, and generated several other chemicals different from PXM. But the PXM treated with the high dose of UVA could not induce positive patch-test reactions in many of the animals contact-sensitized with TMS or TOS. The cross-reacting hapten generated from PXM by UVA treatment may not be stable in the absence of carrier proteins. These results taken together indicate that the PXM photosensitivity in man is induced by contact-sensitization with TMS, as shown in our animal model, and then is photoallergic in nature. But the identity of the cross-reacting substance remains unknown.

[Lobular carcinoma of the male breast--a case report].

Lobular carcinoma of the male breast is very rare, because lobules do not exist in the male mammary gland. Seven cases of lobular carcinoma of the male breast have been reported in Europe and U.S.A., although no case in Japan. We encountered a very rare case of the lobular carcinoma of 74-year-old male breast. Histopathological examinations of both primary tumor and recurrent tumors of the skin led to the diagnosis of lobular carcinoma.

Cross-reactivity between sensitivity to thimerosal and photosensitivity to piroxicam in guinea pigs.

Piroxicam (PXM) is a nonsteroidal anti-inflammatory drug which may induce a photosensitive eruption shortly after administration. We examined whether animals sensitized to thimerosal developed a photosensitivity to PXM. Male Hartley strain guinea pigs were sensitized to thimerosal, thiosalicylate and PXM separately. The open patch test was used to evaluate sensitization to each drug and cross-reactions between the drugs. Animals sensitized to thimerosal exhibited positive patch test reactions to thiosalicylate and positive photopatch test reactions to PXM. Both those sensitized to thiosalicylate and to PXM showed positive patch test reactions to PXM. This study demonstrated that thimerosal induces cross-sensitivity to PXM in vivo and that the common active component among these compounds may be thiosalicylate.

A probable role for vaccines containing thimerosal in thimerosal hypersensitivity.

We patch tested 141 patients with 0.05% aq. thimerosal and 222 patients with 0.05% aq. mercuric chloride, including 63 children. The frequency of positive patch test reactions to thimerosal was 16.3%. There was a marked preponderance in the young age groups after vaccination, while none of 36 infants (aged 3-48 months) reacted to thimerosal. Positive reactions to mercuric chloride were found in 23 (10.4%) of 222 patients. We also sensitized guinea pigs with diphtheria-pertussis-tetanus (DPT) vaccine containing 0.01% thimerosal and succeeded in inducing hypersensitivity to thimerosal. From patch testing in humans and animal experiments, it is suggested that 0.01% thimerosal in vaccines can sensitize children, and that hypersensitivity to thimerosal is due to the thiosalicylic part of the molecule and correlates with photosensitivity to piroxicam.

Treatment of cutaneous T-cell lymphomas (CTCL) with extracorporeal photochemotherapy--preliminary report.

Since August of 1988, we have treated seven CTCL patients with extracorporeal photochemotherapy, including two with tumor-stage mycosis fungoides (MF) showing mucinous degeneration, two with plaque-stage MF, and two with erythrodermatous MF. One was withdrawn just after the first trial. For each patient, the phenotypes of peripheral blood lymphocytes were analyzed by flow cytometry in terms of the percentages of OKT11, OKT3, OKT4, Leu9, OKT8, B1, Tac, OKT9, OKIa1, Leu7, Leu3a/4B4, and Leu3a/2H4 cells. These parameters were compared with the clinical responses according to skin score. The two patients with tumors died, but the five patients without tumors did not. Three of the 6 patients responded to the treatment. Side effects that are often associated with standard chemotherapy, such as bone marrow suppression, gastrointestinal symptoms and hair loss, were not observed. One cardiovascular event (1 patient) occurred. No significant changes in T-cell subsets were seen during the course of therapy. These preliminary data suggest that extracorporeal photochemotherapy may be effective for CTCL other than tumor-stage MF.

[IL-2 responsiveness in antigen-specific lymphocyte proliferation test with sulfhydryl drug-sensitized murine lymphocytes--using rapid fluorochromasia assay].

Response of murine lymphnode cells (LNC) sensitized with sulfhydryl drugs to recombinant interleukin 2 (rIL-2) was studied in antigen-specific lymphocyte proliferation test (LPT). Mice were primed with tiopronin (TP) and gold sodium thiomalate (GTM) and the secondary response to LNC was measured in a proliferative assay in vitro. Rapid fluorochromasia assay with propidium iodide (RFP) was used for the quantitative measurement of LPT instead of 3H-thymidine uptake. There was no difference in proliferative response to specific antigen between TP or GTM-primed LNC and control ones. In contrast, a significant proliferation was observed when LNC from sensitized mice were cultured with sensitizing antigen and rIL-2. The strength of response was dependent on the concentration of rIL-2. It was considered that adding rIL-2 to LPT of TP or GTM-sensitized mice enhanced antigen-specific lymphocyte proliferative response and the measurement of IL-2 responsiveness using RFP method might be useful to detect sulfhydryl drug allergy in man.

Evaluation of skin test reactions in patients with non-immediate type drug eruptions.

Skin test reactions were evaluated in 242 patients who appeared to develop delayed type drug eruptions from the clinical course. The patch testing was positive in 62 (31.5%) of 197 patients tested and the intradermal testing in 105 (89.7%) of 117 patients. The positive ratios of intradermal testing were higher in maculopapular (MP), erythema multiforme (EM), and erythrodermic (ED) types than in eczematous (Ecz) type drug eruptions, while those of patch testing were comparatively high in ED, Ecz type, and anticonvulsant-induced drug eruptions. It is considered that the combination of patch testing and intradermal testing is useful for determination of causative drugs in delayed type drug eruptions.

Sulfhydryl drug-induced eruption: a clinical and histological study.

Sulfhydryl drug-induced skin eruptions were studied clinically and histologically in 23 patients. In this study, tiopronin, D-penicillamine, captopril and gold sodium thiomalate were considered to be sulfhydryl drugs, because they have a thiol group or release sulfhydryl compounds. The clinical features included skin eruptions that were maculopapular, erythema multiforme-like, eczematous, psoriasis-like, seborrheic dermatitis-like, Gibert-like, lichen planus-like, and pemphigus-like. These clinical findings were reminiscent of the wide variety of eruptions seen in cutaneous graft-versus-host reactions (GVHR). Histologically, areas of vacuolation and eosinophilic necrosis with a satellite infiltrate of lymphoid cells were seen in the epidermis, and perivascular infiltrates were noted in the dermis. These findings were similar to the histological picture of cutaneous GVHR. In skin tests with sulfhydryl compounds, 19 out of 20 subjects showed positive reactions, and autoantibodies were found in 8 out of 12 subjects tested. Sulfhydryl drugs seem likely to induce immunologic changes in the host and to produce a distinctive reaction similar to that of cutaneous GVHR.