bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of Lilial® as a fragrance sensitizer in a perfume by bioassay‐guided chemical fractionation and structure‐activity relationships
Authors: Arnau E. Giménez , Andersen K. E. , Bruze M. , Frosch P. J. , Johansen J. D. , Menné T. , Rastogi S. C. , White I. R. , Lepoittevin J.‐P.
Published: March 2003

Fragrance materials are among the most common causes of allergic contact dermatitis. The aim of this study was to identify in a perfume fragrance allergens not included in the fragrance mix, by use of bioassay‐guided chemical fractionation and chemical analysis/structure‐activity relationships (SARs). The basis for the investigation was a 45‐year‐old woman allergic to her own perfume. She had a negative patch test to the fragrance mix and agreed to participate in the study. Chemical fractionation of the perfume concentrate was used for repeated patch testing and/or repeated open application test on the pre‐sensitized patient. The chemical composition of the fractions giving a positive patch‐test response and repeated open application test reactions was obtained by gas chromatography‐mass spectrometry. From the compounds identified, those that contained a “structural alert” in their chemical structure, indicating an ability to modify skin proteins and thus behave as a skin sensitizer, were tested on the patient. The patient reacted positively to the synthetic fragrance p‐t‐butyl‐α‐methylhydrocinnamic aldehyde (Lilial®), a widely used fragrance compound not present in the fragrance mix. The combination of bioassay‐guided chemical fractionation and chemical analysis/structure‐activity relationships seems to be a valuable tool for the investigation of contact allergy to fragrance materials.
A skin sensitization safety assessment of a new bleach activator technology in detergent applications
Authors: Roggeband R. , Helmlinger G. , Smith I. , Wilhelm K.‐P. , Ryan C. A. , Gerberick G. F.
Published: March 2003

A new chemical called nonanoyl amido caproylacid oxybenzenesulphonate (NACAOBS) is being developed for use as a bleach activator in laundry detergents. Bleach activators, like NACAOBS, are typically used at levels between 2% and 6% in laundry detergents. NACAOBS is stable in aqueous solutions, but undergoes rapid perhydrolysis when combined with water and peroxygen bleach in laundry detergents. Animal testing demonstrated that NACAOBS, as a raw material, is a weak skin sensitizer. Clinical testing, including extended simulated laundry pretreatment, human repeat insult patch testing and home use testing was then undertaken, following sufficient reassurance of 1) the weak sensitization potential of the substance, 2) its rapid degradation in laundry wash solutions and, consequently, 3) low‐to‐negligible consumer dermal exposures to the native substance. Results confirmed the skin sensitization safety profile of laundry detergents containing NACAOBS, namely the absence of any reaction suggestive of contact sensitization (even under exaggerated dermal exposure conditions in a detergent matrix), and a skin compatibility profile comparable to that of current detergents. Further confirmation of the skin safety profile was obtained from a successful 12‐month market test of a granular detergent containing 3.6% of the new substance, during which not a single adverse skin reaction was reported. In addition, NOBS (an oxybenzenesulphonate structural analogue to NACAOBS) has similar toxicological properties and has been safely marketed in detergents at similar levels for many years. It can be concluded that the likelihood of NACAOBS to induce skin sensitization or even elicit allergic reactions in consumer detergent use scenarios is negligible.
Three‐dimensional imaging of the craniofacial complex
Authors: Nguyen Can X. , Nissanov Jonathan , Öztürk Cengizhan , Nuveen Michiel J. , Tuncay Orhan C.
Published: March 2003

Orthodontic treatment requires the rearrangement of craniofacial complex elements in three planes of space, but oddly the diagnosis is done with two‐dimensional images. Here we report on a three‐dimensional (3D) imaging system that employs the stereoimaging method of structured light to capture the facial image. The images can be subsequently integrated with 3D cephalometric tracings derived from lateral and PA films ( http://www.clinorthodres.com/cor‐c‐070). The accuracy of the reconstruction obtained with this inexpensive system is about 400 μ.
Palatally displaced upper lateral incisors: relapse after orthodontic treatment and its correlation with dentoskeletal morphology
Authors: Okamoto M. , Takada K. , Yasuda Y. , Bishara S.
Published: March 2003

The purpose of the present study was to determine whether the relapse tendency of the palatally positioned upper lateral incisor differs in patients treated with or without premolar extraction, and if there is any correlation between the amount of upper lateral incisor relapse and pretreatment dentoskeletal morphology or post‐treatment changes. Forty‐six patients with bilateral palatally displaced upper laterals who also exhibit maxillary dental constriction were separated into two groups: a premolar extraction (30 cases) group and a non‐extraction (16 cases) group. All subjects had undergone orthodontic treatment with quad helix and edgewise appliances, followed by a 2‐year retention period. Differences in the amount of the upper lateral incisor relapse and their correlations with the dentoskeletal morphology before and after treatment were determined on the lateral and postero‐anterior cephalograms and dental casts. Results revealed that the upper lateral incisor relapse in the extraction group was significantly greater (p=0.0002) than the relapse in the non‐extraction group. There was a positive correlation between incisor relapse and the distance of lateral incisor movement in both groups (r=0.539; p=0.030). Relapse in the non‐extraction group was correlated with the widths of the upper dental arch (r≤−0.507, p≤0.044), with the naso‐maxillary variables before treatment (r=−0.514, p=0.041), and also with changes in the upper inter‐premolar and inter‐molar widths during retention (r=0.514, p=0.040).
Maxillary expansion: a meta analysis
Authors: Schiffman Patricia H. , Tuncay Orhan C.
Published: March 2003

The utility of maxillary expansion has been equivocal for more than 100 years. The advent of meta‐analysis and evidence‐based learning has provided an opportunity to look objectively at this treatment modality. Medline was searched from 1978 to 1999 for all studies examining the stability of transverse expansion of the human maxilla using initial search terms of maxillary expansion and palatal expansion which were limited to those English language and human subjects. The more than 5000 articles were reduced to 12 based on the defined inclusion and exclusion criteria. The two investigators participating in the study were blinded, the studies’ authors and origins blacked out and the evaluation coded and scored. A cumulative ‘Meta evaluation score’ was computed for each study. Six studies remained for the final analysis. The mean expansion after adjustment according to the principles of meta analysis was 6.00 mm with a standard deviation of 1.29 mm. Of the 6‐mm average, 4.89 mm was retained while wearing retainers. Five of the papers provided retention data and post‐retention data, but only three studies provided both retention and post‐retention data. The average age of patients in these reports was 10.8 years. The 6‐mm average expansion with retention in the short‐term (<1 year) yielded a 4.71‐mm residual expansion. Subsequently, this expansion during the short‐term post‐retention period was reduced to 3.88 mm. Finally, in the long‐term post‐retention study period only 2.4 mm of the residual expansion was reported to have remained. This 2.4 mm of expansion remaining after more than a year or more of post‐retention period was no greater than what has been documented as normal growth. There is insufficient data to conclude that any useful expansion beyond that can be expected through normal growth was retained.
The microanatomy of the distal arrector pili: possible role for α1β1 and α5β1 integrins in mediating cell‐cell adhesion and anchorage to the extracellular matrix
Authors: Mendelson Jeri Kersten , Smoller Bruce R. , Mendelson Bruce , Horn Thomas D.
Published: March 2003

The arrector pili (AP) muscle is a small band of smooth muscle that attaches proximally to the bulge area of the pilosebaceous apparatus in the reticular dermis and extends up toward the epidermis. The distal anatomy of the AP and the anchorage mechanism allowing hair erection have not been previously described. Integrins are likely candidates mediating this attachment. Immunohistochemical techniques were used to determine the distribution of the following integrins: α1, α2, α3, α4, α5, α6 and β1 as well as fibronectin. Frozen human scalp tissue was sectioned in traditional planes, obliquely and horizontally to visualize microanatomy in three dimensions. Histological examination revealed that the distal portions of smooth muscle fibers splay extensively between collagen bundles of the upper dermis. Integrin subunits α1, α5 and β1 were expressed by the AP muscle. Analysis of the relative density of immunoreactivity in digitized sections revealed increased α5 subunit expression at the extracellular matrix (ECM)‐muscle interface. These data suggest that anchorage of the AP muscle to the ECM is via α5β1 integrin and α1β1 integrin functions in muscle cell‐cell adhesion. Extensive splaying of smooth muscle fibers may allow increased surface area contact between the ECM and smooth muscle cells expressing peripherally situated α5 integrin.
Generalized pruritic eruption with suprabasal acantholysis preceeding the development of bullous pemphigoid
Authors: Barnadas María A. , Pujol Ramón M. , Curell Román , Matías‐Guiu Xavier , Alomar Agustín
Published: March 2003

We report a patient who presented with a papular pruritic eruption of a 3‐month duration that histologically showed suprabasal acantholysis accompanied of an eosinophilic inflammatory infiltrate that was consistent with the diagnosis of Grover's disease. Later, erythematous plaques and vesicles appeared which showed a histopathological pattern of eosinophilic spongiosis. The direct immunofluorescence (DIF) study showed lineal IgG and C′3 at the dermal epidermal junction which was consistent with the diagnosis of bullous pemphigoid. No anti‐intercellular deposits of immunoglobulin G (IgG) or C′3 were observed. We consider that suprabasal acantholysis may represent the early phase of bullous pemphigoid.
Immunohistochemical analysis of cytokeratin expression in reactive eccrine syringofibroadenoma‐like lesion: a comparative study with eccrine syringofibroadenoma
Authors: Ohnishi Takamitsu , Watanabe Shinichi , Nomura Kazuo
Published: March 2003

In addition to solitary eccrine syringofibroadenoma (ESFA), there is another type of ESFA which is associated with underlying dermatoses (reactive ESFA‐like lesion). Five lesions in 4 patients of reactive ESFA‐like lesion were analyzed by an immunohistochemical method using 13 kinds of anti‐cytokeratin (CK) antibodies. Two cases of solitary ESFA were also studied by the same procedure for comparison. Suprabasal staining pattern of AE1 and MNF116, which stain CKs 6, 16 and 17, markers of hyperproliferative state, was observed diffusely in 5 lesions of reactive ESFA‐like lesions except for focal negative staining in one case, and was observed focally in one case of solitary ESFA. Furthermore, differentiation‐specific cytokeratin expression was reduced in 3 of 5 lesions of reactive ESFA‐like lesions. Both ESFA and reactive ESFA showed basically similar immunoreactivity suggesting differentiation toward the dermal duct. The above slight difference in immunoreactivity between both lesions may be explained due to inflammatory infiltrates associated with underlying dermatoses.
Histopathological features of flexural melanocytic nevi: a study of 40 cases
Authors: Rongioletti Franco , Ball Russell A. , Marcus Rosilyn , Barnhill Raymond L.
Published: March 2003

Melanocytic nevi in certain locations such as the genital and acral sites may have atypical histologic features simulating melanoma. We studied the microscopic findings of 40 melanocytic nevi of flexural sites (axilla, umbilicus, inguinal creases, pubis, scrotum and perianal area) to verify if flexural nevi show distinctive features similar to melanocytic nevi of the genital skin. The patients were young (mean age 20 years), the lesions were mostly removed for cosmetic reasons and we are not aware of any deaths or complications related to the removed nevi. We found that 22 (55.5%) out of 40 flexural nevi had “a nested and dyshesive pattern” similar to the melanocytic nevi of genital skin. This pattern was characterized by the confluence of enlarged nests with variation in size, shape and position at the dermo‐epidermal junction and by the diminished cohesion of melanocytes. Dermatopathologists should pay attention to the “nested and dyshesive pattern” of flexural nevi that may mimick hystologic changes of melanoma.
Epithelioid blue nevus: a rare variant of blue nevus not always associated with the Carney complex
Authors: Moreno Carmen , Requena Luis , Kutzner Heinz , De La Cruz Alberto , Jaqueti Gerardo , Yus Evaristo Sánchez
Published: March 2003

Epithelioid blue nevus is a rare variant of blue nevus that has been recently described in patients with Carney complex. Some of the patients with Carney complex have multiple epithelioid blue nevi and a familial history of similar lesions is often recorded. Epithelioid blue nevus consists of an intradermal melanocytic nevus composed of polygonal epithelioid cells laden with melanin. Neoplastic cells show no maturation at the base of the lesion and, in contrast with the usual stromal changes in blue nevi, epithelioid blue nevus exhibits no fibrosis of the dermis. We have studied three cases of epithelioid blue nevus in three patients with no evidence of Carney complex. The lesions were solitary and there was no family history of similar lesions. Therefore, epithelioid blue nevus is a distinctive variant of blue nevus that may also appear as a sporadic lesion and is not always associated with Carney complex.
Lymphoma‐ and leukemia‐associated cutaneous atypical CD30+ T‐cell reactions
Authors: Su Lyndon D. , Duncan Lyn M.
Published: March 2003

Cutaneous CD30+ lymphoid infiltrates appear cytologically atypical and occasionally may be misinterpreted as recurrent disease when they occur in patients treated for other primary hematologic malignancies. We recently encountered two such cases and present our findings. One patient with B‐cell lymphoma and another with myeloid leukemia developed cutaneous eruptions after chemotherapy displaying highly atypical perivascular lymphoid cells on histology that mimicked recurrent disease. In both cases, the lymphocytes were CD30+ T cells by immunohistochemistry. The skin lesions spontaneously resolved and have not recurred. Because one case was initially misinterpreted as recurrent leukemia, we conclude that close clinical correlation and immunophenotypic confirmation should be done for atypical cutaneous lymphoid infiltrates in patients with primary hematologic malignancies. We discuss the differential diagnosis of atypical CD30+ infiltrates in this setting, which include recurrent lymphoma or myeloid leukemia, primary cutaneous anaplastic large cell lymphoma (ALCL), lymphomatoid papulosis (LyP), carbamazepine‐induced CD30+ pseudolymphoma, viral infection and an atypical eruption of lymphocyte recovery.
Multinucleate cell angiohistiocytoma: report of two cases with no evidence of human herpesvirus‐8 infection
Authors: Sass Ursula , Noel Jean‐Christophe , André Josette , Simonart Thierry
Published: March 2003

Multinucleate cell angiohistiocytoma (MCA) is a vascular tumor of unknown pathogenesis. Possible misinterpretation of this disorder with Kaposi's sarcoma (KS), a human herpesvirus‐8 (HHV‐8)‐associated tumor, prompted us to look for this virus in two women with MCA. None of the multiple skin specimens obtained from both our patients produced amplified HHV‐8 DNA. Using a cell culture methodology similar to that used for KS, we established cell cultures from MCA lesions. While KS spindle cells are known to exhibit in vitro invasive properties and can be grown up to more than 20 passages, the MCA‐derived cells were short‐lived and were not able to traverse basement membranes. Taken together, our data support the hypothesis that MCA is not a neoplasm but a benign vascular proliferation which is clearly distinguishable from KS.
Apoptosis and expression of Bax/Bcl‐2 proteins in pyogenic granuloma: a comparative study with granulation tissue and capillary hemangioma
Authors: Nakamura Toshitsugu
Published: March 2003

Background: Pyogenic granuloma (PG) has been regarded as a florid expression of granulation tissue (GT) proliferation and shows distinct biological behavior compared to conventional GT. PG has not been examined from a standpoint of apoptosis.

Methods: PG (15 cases), GT (14 cases) and capillary hemangioma (CH, 8 cases) were compared using in situ 3′‐tailing reaction (ISTR), a histochemical method for identifying apoptotic cells, and immunohistochemistry for Ki‐67, Bcl‐2 and Bax proteins, in order to clarify and involvement of apoptosis in the difference of biological characteristics between PG and GT.

Results: PG showed significantly lower ISTR‐labeling indices than GT and CH and more frequent Bcl‐2/Bax expression than GT, whereas Ki‐67‐labeling indices were variable from case to case and did not show any significant differences among any groups.

Conclusions: It is consequently suggested that the low apoptotic rate in PG is closely related to its characteristic rapid growth and is regulated by Bcl‐2 family proteins.
Livedoid vasculopathy in a patient with factor V mutation (Leiden)
Authors: Biedermann Tilo , Flaig Michael J. , Sander Christian A.
Published: March 2003

Background: Frequently, no underlying disease can be detected in patients with livedoid vasculopathy. For these forms, an unknown vaso‐occlusive or thrombogenic process has been accused to play a role. Thus, a patient with livedoid vasculopathy was examined for different parameters which can be involved in coagulopathies.

Methods: Laboratory studies for different autoantigen reactive immunoglobulins, cryoglobulins, and circulating immune complexes were carried out. Besides dermatopathologic examination, a biopsy specimen was analyzed by direct immunoflourescence for immunoglobulin (Ig) and complement deposits. Furthermore, hemostaseological function tests including activated protein C (APC) resistance were undertaken.

Results: Positive only at very low titres were antinuclear antibodies and c‐ANCA, all other parameters were within normal ranges or negative. Direct immunofluorescence revealed IgM, C3 and fibrogen deposits. Hemostaseological function tests demonstrated a pathologic activated protein c resistance and PCR analysis a heterozygous defect of the factor V (Leiden).

Conclusions: The diagnosis of livedoid vasculopathy associated with factor V mutation (Leiden) was made. Since the underlying cause for livedoid vasculopathy often remains unknown, we suggest that hemostaseological function tests including APC resistance and factor V gene mutation analysis should be carried out. Further studies have to follow in order to elucidate the role of mutant factor V in livedoid vasculopathy and in cutaneous ulcerations.
Rippled‐pattern sebaceous trichoblastoma
Authors: Graham Brad S. , Barr Ronald J.
Published: March 2003

Background: There is a large spectrum trichoblastoma; of which, several histologic variants have been described including a rippled‐pattern variant. Three cases of rippled‐pattern trichoblastoma are described which also exhibited definitive foci of sebaceous differentiation.

Methods: Three cases were retrieved from the archives of the Dermatopathology Laboratory at the University of California Irvine (Orange, CA, USA). All specimens were stained with hematoxylin and eosin (H&E). In addition, sections were submitted for immunohistochemical studies with epithelial membrane antigen (EMA).

Results: All three biopsies were composed of well‐circumscribed multiple variously sized tumor lobules present in the upper to deep dermis comprised of with rounded or slightly elongated basaloid cells with scant eosinophilic cytoplasm. The lobules were separated by a slightly hyalinized stroma. The unique finding present in all three specimens was a peculiar arrangement of the basaloid cells in linear rows parallel to one another. This gave the tumors a rippled pattern similar to the palisading of nuclei of Verocay bodies seen in schwannomas. In addition all three biopsies showed definite sebaceous differentiation.

Conclusions: Three additional cases of rippled‐pattern trichoblastoma are presented. All three were located on the scalp and showed additional features of foci of sebaceous differentiation. No associations with Muir‐Torre Syndrome were found in these patients. Because this appears to be a distinct variant within the large spectrum of trichoblastoma, the term rippled‐pattern sebaceous trichoblastoma is suggested.
Transepithelial elimination of cutaneous vulval granuloma inguinale
Authors: Ramdial Pratistadevi K. , Kharsany Ayesha B. M. , Reddy Roshilla , Chetty Runjan
Published: March 2003

Background: Transepithelial elimination (TEE), a distinct and well‐known entity, is a process during which the skin eradicates undesirable or irritative dermal substances through intact epidermis or follicular epithelium by passive or active means. Although TEE is being described in an increasing number and range of pathological processes, to date, TEE of granuloma inguinale (GI) remains unrecorded in the English‐language literature. The aims of this study were: 1) To appraise the light microscopic and ultrastructural morphological epidermal changes that are associated with TEE of cutaneous vulval GI; and 2) To determine the role of intra‐epidermal leucocytes and histiocytes in the pathogenesis of TEE of vulval GI.

Methods: This is a retrospective 9‐year histopathological review of all cases diagnosed and coded as vulval granuloma inguinale in the Department of Anatomical Pathology, Nelson R. Mandela School of Medicine, University of Natal, Durban, South Africa. Ultrastructural evaluation was performed on selected cases using a Jeol transmission electron microscope.

Results: Of 53 skin biopsies from 47 patients with vulval GI, 43 were suitable for the study. The age range of patients was 15–40 years (mean age=22 years). There were eleven papular, twelve nodular, seven verrucous and thirteen ulcerative lesions. Donovan bodies within macrophages, free‐lying Donovan bodies and dense aggregates of neutrophils and plasma cells were seen in the dermis of all biopsies. There was consistent overlying pseudoepitheliomatous hyperplasia. The dermal inflammatory infiltrate hugged the dermo‐epidermal junction and appeared entrapped between elongated and acanthotic epidermal rete ridges and pegs. Transepidermal neutrophil microabscesses, histiocytes containing Donovan bodies and neutrophilic and histiocytic fragmentation were present. A variable number of free‐lying and intra‐histiocytic Donovan bodies and neutrophils were present on the surface of the epidermis. On ultrastructural investigation epidermal spongiosis, intracellular oedema, free‐lying, intra‐neutrophilic and intra‐histiocytic Donovan bodies, and intact and degenerating neutrophils and histiocytes were evident between keratinocytes. The degenerative histiocytes demonstrated marked vacuolation, mitochondrial swelling and bacilli within phagolysosomal vacuoles, bound by intact or disrupted limiting membranes.

Conclusion: The inflammatory infiltrate at the epitheliomesenchymal interface, pseudoepitheliomatous hyperplasia, intra‐epidermal accumulation and disintegration of neutrophils and histiocytes, and the associated release of lytic enzymes, play important contributory roles in TEE of GI. TEE of infectious agents is a poorly recognised mechanism of spread of infectious diseases and represents a public health hazard. In cutaneous vulval GI, TEE is highlighted as a hitherto unrecognised, potential method of spread of Calymmatobacterium granulomatis.
E‐cadherin expression in wound healing of mouse skin
Authors: Kuwahara Masamitsu , Hatoko Mitsuo , Tada Hideyuki , Tanaka Aya
Published: March 2003

Background: E‐cadherin has been studied extensively in other systems but little attention has been paid to its role in wound healing. We investigated E‐cadherin expression in epithelial wound healing in vivo by focusing on the migrating cells in the epithelial tongue and the mitotic cells in the non–injured side apart from the original wound edge.

Methods: Round full‐thickness excisional wounds (6 mm in diameter) and full‐thickness incisional wounds were prepared dorsally in mice. On various days after the operation, E‐cadherin expression was examined by immunohistochemical staining using a monoclonal antibody specific for E‐cadherin.

Results: In both models, the level of E‐cadherin expression did not decrease on the 1st postoperative (P.O.) day. After the 2nd P.O. day, E‐cadherin expression decreased in cells at a site 500 μm apart from the original wound edge. After the 3rd P.O. day, decreased expression was also observed in cells at the top and in the basal layer of the epithelial tongue. This decreased expression continued for 1 or 2 days after the meeting of the epithelial tongue. There was no significant difference in the expression of E‐cadherin between two models.

Conclusions: The results suggested that E‐cadherin expression decreases in epithelial cells. This decrease may depend on the activity of migration and mitosis. In addition, the change was similar in both the excisional and incisional wounds.
Matrix metalloproteinases and their inhibitors in oral lichen planus
Authors: Zhou Xijing J. , Sugerman Philip B. , Savage Neil W. , Walsh Laurence J.
Published: March 2003

Background: Oral lichen planus (OLP) is characterized by a sub‐epithelial lymphocytic infiltrate, basement membrane (BM) disruption, intra‐epithelial T‐cell migration and apoptosis of basal keratinocytes. BM damage and T‐cell migration in OLP may be mediated by matrix metalloproteinases (MMPs).

Methods: We examined the distribution, activation and cellular sources of MMPs and their inhibitors (TIMPs) in OLP using immunohistochemistry, ELISA, RT‐PCR and zymography.

Results: MMP‐2 and ‐3 were present in the epithelium while MMP‐9 was associated with the inflammatory infiltrate. MMP‐9 and TIMP‐1 secretion by OLP lesional T cells was greater than OLP patient (p<0.01) and healthy control subject (p<0.001) peripheral blood T cells. MMP‐9 and TIMP‐1 mRNA levels were greater in OLP lesional T cells compared with healthy control subject peripheral blood T cells (p<0.01). Tumor necrosis factor (TNF)‐α upregulated OLP lesional T‐cell MMP‐9 (not TIMP‐1) mRNA and secretion (p<0.05). The in vitro activation rate of MMP‐9 from OLP lesional T cells was greater than that from OLP peripheral blood T cells (p<0.05).

Conclusion: T‐cell‐derived MMP‐9 may be involved in the pathogenesis of OLP. Relative over‐expression of MMP‐9 (compared with TIMP‐1) may cause BM disruption and facilitate intra‐epithelial T‐cell migration in OLP.
Follicular mycosis fungoides. A histopathologic analysis of nine cases
Authors: Flaig Michael J. , Cerroni Lorenzo , Schuhmann Kathrin , Bertsch Hans Peter , Kind Peter , Kaudewitz Peter , Sander Christian A.
Published: March 2003

Background: The spectrum of mycosis fungoides is exceedingly broad. Many different variants have been described, based on both clinical appearance and histological pattern. A rare form which shows preferential infiltration of hair follicles by malignant lymphocytes is follicular mycosis fungoides.

Methods: We reviewed our experience with nine cases of follicular mycosis fungoides.

Results: The unifying feature was infiltration of the hair follicle epithelium by atypical lymphocytes causing varying degrees of damage to the hair follicles. In some specimens the lymphocytes displayed only minor atypia leading to a misinterpretation as pseudolymphoma. Gene rearrangement studies were particularly helpful for establishing a diagnosis of malignant lymphoma. Additionally, epidermotropism of lymphocytes, eosinophils and mucin deposition were present to varying degrees. Mucin makes the distinction from mycosis fungoides‐associated follicular mucinosis difficult. We found both dermal mucin and a follicular mucinosis pattern present at different stages of disease in the same patient.

Conclusions: We suggest the term mycosis fungoides‐associated follicular mucinosis should be replaced by follicular mycosis fungoides in future lymphoma classification schemes.
Primary cutaneous adenosquamous carcinoma: a case report and review of the literature
Authors: Azorín Daniel , López‐Ríos Fernando , Ballestín Claudio , Barrientos Nuria , Rodríguez‐Peralto José Luis
Published: March 2003

Background: Adenosquamous carcinoma (ASC) of skin is a rare but distinctive neoplasm that usually exhibits an aggressive course. To date, 13 well‐documented and undisputed cases of primary cutaneous ASC have been reported. This term has been used for tumors with better prognosis, such as mucoepidermoid carcinomas and acantolytic squamous cell carcinomas, originating confusion. We report a primary cutaneous ASC and review the literature.

Methods: In this report a woman with primary ASC of the skin was studied. Histopathological examination and inmunohistochemical stains were performed.

Results: The tumor had two components: conventional squamous cell carcinoma merging with adenocarcinoma. After a local recurrence and lymph node metastases, the patient has no evidence of disease 8 months later.

Conclusions: Pathologists should reserve the term ASC for tumors exhibiting the above mentioned appearance. In such circumstances, a metastatic origin must always be excluded.
A giant verruciform xanthoma
Authors: Agarwal‐Antal Neera , Zimmermann James , Scholz Theresa , Noyes R. Dirk , Leachman Sancy A.
Published: March 2003

Background:  Verruciform xanthoma (VX) is a rare, benign neoplasm arising predominantly in the oral cavity, but it has been reported to occur on the genital skin and mucosa as well. VX has also been described in association with epidermal nevi and squamous cell carcinoma. Because of the clinical and histologic similarities between VX and condyloma acuminata, and a recent report of HPV 6 in association with VX, we investigated the role of human papilloma virus (HPV) in the development of this entity.

Methods:  In situ hybridization and a nested PCR approach utilizing degenerate primers were utilized to establish whether HPV infection could be playing a role in the development of the VX.

Results:  In situ hybridization failed to identify HPV DNA. The highly sensitive nested PCR approach also failed to detect HPV DNA.

Conclusions:  The failure to detect HPV DNA, even by very sensitive methods, provides strong evidence that our case of VX is not an HPV‐induced lesion. A review of other possible etiologies, including alternative infectious agents and genetic associations, are discussed.
Nanobacteria and calcinosis cutis
Authors: Morgan Michael B.
Published: March 2003

Background:  The nanobacteria are a recently characterized group of extremely small bacteria capable of precipitating calcium salts implicated in the pathogenesis of urinary calculi and calcific atherosclerosis. The pathogenesis of calcinosis cutis and its significance in conjunction with a variety of unrelated scarring and pre‐existing cutaneous entities are incompletely understood.

Methods:  A series of cases, including basal cell carcinoma with dystrophic calcification, subepidermal calcified nodule, pilomatricoma, and tumoral calcinosis, were ultrastructurally examined for the presence of Nanobacteria sp.

Results:  All cases, including three basal cell carcinomas, two subepidermal calcified nodules, three cases of pilomatricoma, and two cases of tumoral calcinosis, were negative for Nanobacteria.

Conclusions:  The dystrophic calcification that occurs in conjunction with the above entities does not likely involve a bacterial‐induced etiology. The cause of these entities remains unknown.
Primary cutaneous CD30 (Ki‐1)‐positive non‐anaplastic B‐cell lymphoma
Authors: Herrera Enrique , Gallardo María , Bosch Ricardo , Cabra Blanca , Aneri Vicente , Sánchez Purificación
Published: March 2003

Background:  The CD30 (Ki‐1)‐positive lymphoproliferative disorders show a non‐epidermotropic infiltrate of large‐sized pleomorphic T cells, being extremely rare those that develop from B cells.

Clinical case:  A 51‐year‐old white man presented with a 8×10 cm lobulated scalp tumor that had developed during the previous 8 months. Histopathology demonstrated a proliferation of medium and large‐sized non‐anaplasic lymphocytes. The tumor cells (CD45+) expressed B phenotype (CD20+, CD3) and were CD30 (Ki‐1) positive. The extension study revealed no extracutaneous involvement and the lesion resolved following chemotherapy. Two years later, after six cycles of chemotherapy that followed the CHOP protocol the patient remained asymptomatic.

Conclusions:  We report a patient with a diffuse lymphoma of medium and large‐sized B phenotype cells on the scalp that showed the unusual characteristic of being both non‐anaplastic and CD30 (Ki‐1) positive.
Multinucleate cell angiohistiocytoma: a fibrohistiocytic proliferation with increased mast cell numbers and vascular hyperplasia
Authors:   Lluís Puig, Fernández‐Figueras María‐Teresa , Bielsa Isabel , Lloveras Betlem ,   Agustín Alomar
Published: March 2003

Background: Multinucleate cell angiohistiocytoma (MCAH) is an uncommon lesion clinically characterized by multiple papules usually located on the face and acral regions of elderly women. Histopathologically, MCAH is characterized by dermal vascular hyperplasia associated with increased number of factor XIIIa‐positive fibrohistiocytic cells and multinucleate cells with scalloped borders.

Methods: We report the clinical, histopathological and immunohistochemical features of three cases of MCAH, with ulstrastructural study in one of them. The patients were a woman and two men of 56, 40 and 70 years of age, respectively. They all had multiple dull‐red papules, which had appeared over several years and were located on the face, the trunk and the dorsa of the hands, respectively.

Results: The reticular dermis presented a fibrohistiocytic proliferation of factor XIIIa‐positive cells, with abundant bizarre multinucleate cells and vascular hyperplasia. Increased mast cell numbers were seen in all cases, often in apposition to multinucleate cells.

Conclusion: Histopathological differential diagnosis of MCAH includes mainly angiofibromas and dermatofibromas, even though vascular hyperplasia can be prominent and has led to many authors to classify MCAH among vascular tumors. Bizarre multinucleate cells can be found in reactive, neoplastic and inflammatory lesions in many sites of the body, and mast cells can play a role in their morphogenesis.
Reduction of expression of tuberin, the tuberous‐sclerosis‐complex‐gene‐2 product in tuberous sclerosis complex associated connective tissue nevi and sporadic squamous and basal cell carcinomas
Authors: Wienecke Ralf , Klemm Eckart , Karparti Sarolta , Swanson Neil A. , Green Andrew J. , DeClue Jeffrey E.
Published: March 2003

Background: Patients affected with tuberous sclerosis complex (TSC) are prone to the development of multiple benign tumors of the skin and other organs. Tuberin, the protein product of the tuberous‐sclerosis‐complex‐2 tumor suppressor gene (TSC2) has been shown to inhibit cell proliferation. In TSC associated kidney tumors and sporadic brain tumors the loss/reduction of tuberin has been shown.

Methods: Specimens of nine squamous cell carcinomas (SCC) and five basal cell carcinomas (BCC) from patients without TSC and six biopsies of connective tissue nevi (CTN) of patients with TSC were obtained. Specimens were analyzed by immunoblotting for the expression of tuberin.

Results: Absent or reduced levels of tuberin were detected in the dermal parts of three of six shagreen patches, two of five BCC, and four of nine SCC.

Conclusions: In tumors/hamartomas of patients with TSC the complete loss of TSC2 and tuberin is a mechanism which could be shown for CTN, thereby excluding the possibility of haploinsufficiency of TSC2. In a substantial number of cutaneous BCC and SCC the loss or downregulation of tuberin seems to be epigenetic, as alterations of TSC2 are not known in these tumors. The absence or reduction of tuberin might contribute to their proliferation.
Angiofibroblastoma of the skin: a report of seven cases in support of a distinctive entity
Authors: Diaz‐Cascajo C. , Schaefer D. , Borghi S.
Published: March 2003

Background:  Angiofibroblastoma of the skin is a recently described benign tumor with fibroblastic differentiation. The tumor is composed of stellate and spindle fibroblasts embedded in a fibromyxoid and fibrous matrix that contains numerous capillary‐sized blood vessels.

Methods:  All cases of fibromyxoid tumors of the skin from the files of two dermatopathologic centers and from consultation cases, together with clinical data and histopathologic specimens, were reviewed. Additionally, immunohistochemical studies were performed in all cases.

Results:  Seven cases of angiofibroblastoma of the skin were found, including two cases previously reported. All cases showed similar histopathologic findings. The morphologic versatility of fibroblasts, however, explains some of the microscopic variations that were observed in three cases of this series. Immunohistochemical studies support the fibroblastic nature of the neoplasms.

Conclusions:  Our series provides data suggesting that angiofibroblastoma of the skin represents a distinctive entity, which should be considered in the differential diagnosis of other fibromyxoid tumors of the skin.
Microtubule associated protein (MAP‐2) expression defines the companion layer of the anagen hair follicle and an analogous zone in the nail unit
Authors: Hallman James R. , Fang Dong , Setaluri Vijayasaradhi , White Wain L.
Published: March 2003

Background:  Microtubule associated protein 2 (MAP‐2) is one of a group of polypeptides that are an integral component of the microtubular cytoskeletal structure of the central and peripheral nervous system. During the course of another investigation that utilized immunohistochemistry, MAP‐2 expression was observed in the hair follicle, almost exclusively in the innermost layer of the outer root sheath of the anagen follicle. This innermost layer, the so‐called companion layer, has unique properties that clearly distinguish it from the rest of the outer root sheath. Among these are diminished glycogenation and an intimate association with the Henle's layer, which it directly apposes. Numerous intercellular connections exist between the companion layer and Henle's layer and, in fact, the companion layer accompanies Henle's layer during its vertical ascent in the follicle. Circumferentially oriented keratin filaments have also been demonstrated between the companion layer and Henle's layer, apparently providing structural support to the inner root sheath. Experimentally, disturbances in the keratin filaments of the companion layer in animals ultimately results in destruction of the hair follicle and an alopecia.

Methods:  Immunohistochemical studies for MAP‐2 were performed on 25 additional paraffin‐embedded scalp specimens using standard techniques. Because of the parallels between the follicle and nail, MAP‐2 expression in the nail unit was also investigated in three specimens.

Results:  The presence of MAP‐2 in the companion layer was confirmed in all cases. Intense MAP‐2 expression in the companion layer begins at the B‐fringe (the start of the keratogenous zone with cornification of the Henle's layer of the inner sheath) and extends to the level of the isthmus where the inner root sheath exfoliates. MAP‐2 is also expressed in the upper layers of the nail matrix.

Conclusion: The expression of MAP‐2 almost exclusively in the companion layer is probably related to the unique cytoskeletal structure of this microanatomic layer. Since experimental evidence has shown that the cell cytoskeleton is important to the integrity of the hair follicle, it is probable that MAP‐2 expression is also important and disturbances in its expression could play a role in the pathogenesis of some alopecias. MAP‐2 may play a similar role in the nail matrix.
Parvovirus B19 associated adult Henoch Schönlein purpura
Authors: Cioc Adina M. , Sedmak Daniel D. , Nuovo Gerard J. , Dawood Magdy R. , Smart Gerry , Magro Cynthia M.
Published: March 2003

Background:  Parvovirus B19 has recently been implicated in various vasculitic syndromes including Henoch Schönlein purpura (HSP), Wegener's granulomatosis and microscopic polyarteritis. The association was established through serology, the identification of DNA in the peripheral blood and affected tissues and more recently by RNA localization to cutaneous capillary endothelium. However, direct localization of the viral DNA to the glomerular and cutaneous endothelium in HSP in correlation with the histopathologic findings has not been demonstrated.

Methods:  Skin and kidney biopsy tissues were processed for hematoxylin and eosin, immunofluorescent, polymerase chain reaction (PCR) and reverse transcriptase in situ PCR studies.

Case presentation:  A 64‐year‐old‐female presented with palpable purpura and nephrotic range proteinuria. Kidney and skin biopsies showed IgA‐associated mesangioproliferative glomerulonephritis and IgA‐associated leukocytoclastic vasculitis, respectively. A diagnosis of HSP was rendered. Her clinical course was refractory to prednisone. Parvovirus B19 DNA and tumor necrosis factor α DNA were identified in the dermal and glomerular capillary endothelial cells and surrounding dermal inflammatory cells.

Conclusion:  This is the first documentation of B19 localization to dermal and glomerular capillary endothelium in HSP. It is important to recognize parvovirus B19‐associated adult HSP cases, as the treatment of choice is intravenous gamma globulin in concert with anti‐TNFα therapy. In contrast immunosuppressive therapy may lead to a persistent and/or worsening disease course.
Alcohol, Drug Abuse, and Mental Health Care for Uninsured and Insured Adults
Authors: Wells Kenneth B. , Sherbourne Cathy Donald , Sturm Roland , Young Alexander S. , Audrey Burnam M.
Published: March 2003

ObjectiveTo compare adults with different insurance coverage in care for alcohol, drug abuse, and mental health (ADM) problems.

Data Sources/Study Setting.From a national telephone survey of 9,585 respondents.

Design.Follow‐up of adult participants in the Community Tracking Study.

Data Collection.Self‐report survey of insurance plan (Medicare, Medicaid, unmanaged, fully, or partially managed private, or uninsured), ADM need, use of ADM services and treatments, and satisfaction with care in the last 12 months.

Principal Methods.Logistic and linear regressions were used to compare persons by insurance type in ADM use.

Principal FindingsThe likelihood of ADM care was highest under Medicaid and lowest for the uninsured and those under Medicare. Perceived unmet need was highest for the uninsured and lowest under Medicare. Persons in fully rather than partially managed private plans tend to be more likely to have ADM care and ADM treatments given need. Satisfaction with care was high in public plans and low for the uninsured.

Conclusions.The uninsured have the most problems with access to and quality of ADM care, relative to the somewhat comparable Medicaid population. Persons in fully managed plans had better rather than worse access and quality compared to partially managed plans, but findings are exploratory. Despite low ADM use, those with Medicare tend to be satisfied. Across plans, unmet need for ADM care was high, suggesting changes are needed in policy and practice.
p63 expression in normal human epidermis and epidermal appendages and their tumors
Authors: Tsujita‐Kyutoku Miki , Kiuchi Katsuji , Danbara Naoyuki , Yuri Takashi , Senzaki Hideto , Tsubura Airo
Published: March 2003

Background:  p63, a member of the p53 gene family, is expressed in basal cells of several different organs.

Methods:  The immunoreactivity of p63 was examined in normal human epidermis and epidermal appendages and their tumors, and compared with proliferative activity as evaluated by Ki‐67.

Results:  In normal skin, p63 expression was seen in basal/suprabasal cells of the epidermis, outer root sheath and hair matrix cells of the hair follicle, seboblast situated in the outermost layer of sebaceous glands, and outer layer cells of the ductal portion and myoepithelial cells of the secretory portion of the sweat glands. p63 expression was confined to the cells forming a continuous basal rim along the normal epithelial structure. In tumors, p63 expression resembled that in normal tissue in that tumor components originating from p63‐positive cells were constantly positive for p63. In normal and tumor tissues, not all p63‐positive cells were positive for Ki‐67.

Conclusions:  p63 expression may be a marker of basal/progenitor cells in tumors of epidermis and epidermal appendages, and may be a diagnostic marker of these tumors.
An evaluation of CASES – an educational audit programme for orthodontists
Authors: Davis M. H. , Clark J. D. , Kerr W. J. S.
Published: March 2003

A regional approach to a national clinical audit programme in orthodontics in the UK is described and evaluated. The programme was designed using the CRISIS criteria for effective continuing education. Programme participants completed duplicate questionnaires on 6 simulated patient scenarios, chosen for their relevance to everyday practice while posing important clinical dilemmas. The participation rate was 77% from hospital‐based practitioners and 29% from specialist practitioners. Feedback to programme participants was given in the form of histograms, and provided a snapshot of national approaches to patient investigation, treatment and expected outcomes. A commentary on the data and references to appropriate articles in the literature were included. Evaluation of the programme by questionnaire survey showed that it was extensively used by hospital‐based practitioners. It is concluded that the model used provided an effective and efficient framework for conducting clinical audit and delivering continuing education to the hospital‐based group.
Student satisfaction with curriculum modifications in a French dental school
Authors: Farge P. , Virieux J. , Doury J.
Published: March 2003

Since 1994, important modifications have been implemented in the dental curriculum in France, and an additional year has been included in the dental curriculum. The 1st year has remained unchanged; it is common to both medical and dental schools and leads to a selection procedure of 1 in 10 dental students. In the new curriculum, the dental student is engaged in a 5‐year programme in dental school (years 2 to 6), as opposed to 4 years in the former programme (years 2 to 5). Basically, this new curriculum emphasises research initiation, links with medical training and offers broader clinical experience. During the academic year 1998–1999, dental schools had 2 different types of students: the 4th year students belonging to the new programme along with the 5th year students in their final year of the old curriculum. Using a specially devised questionnaire, we investigated the students’ perception of their respective training, their motivation and professional plans. At the Faculty of Odontology in Lyon, the new curriculum is perceived as an increased strain by the dental students.