bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatial analysis to identify differentials in dental needs by area‐based measures
Authors: Antunes José Leopoldo Ferreira , Frazão Paulo , Narvai Paulo Capel , Bispo Camila Manoel , Pegoretti Tatiana
Published: March 2003

Objectives: To examine the association between tooth decay and dental treatment needs in 5–12‐year‐old schoolchildren in São Paulo with area‐level indicators of social development. Methods: The present study refers to a representative sample of children from the city of São Paulo, Brazil, comprising 2491 girls and boys attending public and private schools in different areas of the city. The assessment of caries and treatment needs followed the international methodological standards prescribed by the World Health Organization. We used spatial data analysis to describe epidemiological measures distributed by small areas, and to explore hypotheses of ecological association between caries indexes and indicators of social development. Results: Schoolchildren in central districts were less affected by tooth decay and presented fewer dental treatment needs when compared to those in peripheral deprived areas. At the spatial level, average family income, unemployment rate, household overcrowding, and an index of inequality of income distribution were significantly correlated with variables measuring children's caries experience. Conclusions: The heterogeneous distribution of caries indexes by areas of the city indicates higher levels of dental decay in areas of social deprivation. The delimitation of areas with increased risk of caries and greater dental treatment needs should be helpful to public health services for the formulation of policies and the targeting of resources to address these problems.
Maternal risk indicators for childhood caries in an inner city population
Authors: Smith R. E. , Badner Victor M. , Morse Douglas E. , Freeman Katherine
Published: March 2003

Objectives: This study evaluated whether characteristics of mothers, such as high mutans streptococci (MS) level, caries experience, reported sugar consumption and demographic variables, could be important risk indicators of caries for their children.

Methods:  Mothers selected on the basis of the caries status of their 3–5‐year‐old‐children were tested for MS, caries, reported sugar consumption and demographic variables.

Results: We found strong associations between children's caries and their mothers' MS levels (high/low adj. OR = 11.3), maternal active caries (yes/no adj. OR = 4.0) and maternal sugar consumption (high/low adj. OR = 4.2). In this small study, mothers' demographic variables were not associated with the status of caries in their children.

Conclusions: Our findings suggest that maternal high MS levels, maternal active decay and maternal sugar consumption are strong risk indicators for children's caries. Although further study is needed, these three maternal risk indicators, taken together, may prove useful in predicting children's caries risk.
Trauma‐related phenomena in anxious dental patients
Authors: de Jongh A. , Aartman I. H. A. , Brand N.
Published: March 2003

Abstract –

Objectives: The main purpose of this descriptive study was to investigate whether dental anxiety is associated with the occurrence of trauma‐related symptoms (i.e. recurrent memories and a tendency to avoid these memories) associated with earlier traumatic dental experiences.

Methods: A sample of 37 consecutive anxious patients attending a dental fear clinic was assessed prior to dental treatment. The results were compared with those of a sample of 32 consecutive patients of a general dental practice, who served as a reference group.

Results: The proportion of patients who indicated they had had a horrific dental experience at least once in their life did not significantly differ between the anxious group and the reference group. Conversely, significantly more patients (76%) in the anxious group reported suffering from memories of these events. They also showed a higher level of trauma‐related symptomatology as indexed by the Impact of Event Scale (IES). About half of the anxious patients suffered from symptoms typically reported by patients with posttraumatic stress disorder (PTSD). Severity of dental anxiety showed a high correlation with both frequency of intrusions (r = 0.64, P < 0.001) and avoidance of the memories (r = 0.62, P < 0.001).

Conclusions: The results suggest that in anticipation of treatment dentally anxious individuals suffer from a high level of intrusive recollections of earlier dental experiences.
Dual effects of CGRP‐antagonist on allergic contact dermatitis in human skin
Authors: Wallengren Joanna
Published: March 2003

There is increasing evidence of an interaction between the nervous and the immune systems. The aim of this study was to investigate the rôle of calcitonin gene‐related peptide (CGRP) in the modulation of the elicitation of immediate and delayed, immunological and non‐immunological reactions in human skin. CGRP (13 pmol and 39 pmol), and the CGRP‐antagonist, CGRP/8–37/, (50 pmol and 500 pmol) were injected intracutaneously prior to provocation tests. Patients with allergy to nickel were provoked with nickel sulfate epicutaneously, and the reactions were evaluated by a clinical scoring system (guidelines of the International Contact Dermatitis Research Group). Patients with allergy to birch pollen were provoked by a prick test with the allergen, and the volume of the weals was measured. The patients were also provoked with tuberculin (delayed immunologic reaction), benzalkonium chloride (irritant contact dermatitis), UV‐light and benzoic acid (non‐immunologic contact urticaria). The test reactions were estimated by planimetry. CGRP/8–37/ exerted dual effects on allergic contact dermatitis, causing potentiation at a dose of 500 pmol (p=0.004) and inhibition at a dose of 50 pmol (p=0.012). Other reactions were not significantly affected by the pretreatments. The results suggest that CGRP participates in delayed inflammatory reactions, but is not involved in immediate immunologic reactions.
Lymphocyte subset changes in blood and gastrointestinal mucosa after oral nickel challenge in nickel‐sensitized women
Authors: Di Gioacchino Mario , Boscolo Paolo , Cavallucci Enrico , Verna Nicola , Di Stefano Fabio , Di Sciascio Maria , Masci Silvio , Andreassi Maria , Sabbioni Enrico , Angelucci Domenico , Conti Pio
Published: March 2003

This study investigates lymphocyte subsets in both the gastrointestinal mucosa and blood, in patients with nickel allergic contact dermatitis, after 10 mg oral nickel challenge (double‐blind, placebo‐controlled). 6 such patients with cutaneous symptoms induced only by skin contact with nickel (group A), 6 with a flare‐up of cutaneous symptoms after food nickel ingestion (group B) and 6 healthy controls (group C) were enrolled. Blood lymphocyte subsets (CD4, CD45RO, CD8) were analyzed before and after 4 and 24 h from the challenge (test 1, 2, and 3), and intestinal biopsies were performed 2 days later. Challenges were positive in group B and negative in group A and controls. Serum and urine nickel levels significantly increased after nickel ingestion, with no differences between the 3 groups. At test 3, a significant decrease of the all CDs studied was found in group B. Biopsies of this group showed higher levels of CD45RO+ cells in the lamina propria and in the epithelium and lower levels of epithelial CD8+ lymphocytes. This study confirms that ingested nickel may induce flare‐up of cutaneous reactions in some nickel‐allergic patients, independently of the degree of sensitization and the intake of metal. In these patients, oral nickel stimulates the immune system, inducing maturation of T lymphocytes from virgin into memory cells; these latter cells seem to accumulate in the intestinal mucosa. The immunoreaction also involves CD8+ cells, whose role is not yet clear.
Sensitizing potential of chlorothalonil in the guinea pig and the mouse
Authors: Boman Anders , Montelius Johan , Rissanen Riitta‐Liisa , Lidén Carola
Published: March 2003

The fungicide chlorothalonil is used extensively under several tradenames for the protection of various horticultural and fruit crops and bananas against fungal infections. It is also used as fungicide in wood preservation and as a preservative in paints. Clinical experience has shown chlorothalonil to be a contact allergen and several cases of allergic contact dermatitis attributed to chlorothalonil have been described. 2 previous guinea pig maximization test studies have shown the sensitizing potential of chlorothalonil to be high. The sensitizing property of chlorothalonil was studied by us with the predictive test methods the local lymph node assay and the cumulative contact enhancement test. In the local lymph node assay, chlorothalonil induced a dose‐dependent increase in proliferation with a maximal stimulation index of 19.2 and 27.2. In the cumulative contact enhancement test, a statistically significant dose‐dependent high sensitization rate was seen with a maximal sensitization rate of 100%. In conclusion, it is evident that chlorothalonil is an extremely potent contact allergen, inducing sensitization using only topical exposure on intact skin.
Pathological findings in cumulative irritation induced by SLS and croton oil in hairless mice
Authors: Moon Seung Hyun , Seo Koo Il , Han Won Suk , Suh Dae Hun , Cho Kwang Hyun , Kim Jin Jun , Eun Hee Chul
Published: March 2003

It is known that the pathological features of acute irritant contact dermatitis are specific according to the irritant. However, in chronic irritant contact dermatitis, it is not clear whether specific patterns exist. To investigate whether the specific pathology of acute irritant contact dermatitis is sustained in chronic irritant contact dermatitis, sodium lauryl sulfate (SLS) and croton oil were applied 3× a week for 2 weeks on the dorsal skin of hairless mice using Finn Chambers. The pathologic changes induced by irritants at various concentrations were evaluated using H&E and Luna’s staining, as well as immunohistochemistry for 5‐bromo‐2‐deoxyuridine (BrdU), keratin 6 and loricrin. Our results showed that epidermal hyperplasia and inflammatory infiltration were relatively marked in the groups treated with higher concentrations of irritants. These features were more prominent in the 1% croton oil treated group than in the 0.25% SLS treated group. However, lower concentrations of irritants resulted in very similar histological changes, characterized by epidermal hyperplasia with minimal inflammatory infiltration, irrespective of the chemical. Our results suggest that the histological responses to irritants vary with concentration in cumulative irritation, as in acute irritation, but repetitive mild irritation may evoke common histological changes, characterized by epidermal hyperplasia with minimal inflammatory infiltration, irrespective of the chemical used.
Validity and ethics of the human 4‐h patch test as an alternative method to assess acute skin irritation potential
Authors: Robinson Michael K. , McFadden John P. , Basketter David A.
Published: March 2003

For more than 50 years, the Draize rabbit skin irritation test has reigned supreme as the regulatory method of choice for the identification of skin irritant chemicals. To date no in vitro alternative test has been validated as an adequate replacement. However, one potential option, to test the endpoint of concern (skin irritation) in the species of concern (man) has been overlooked. The advent of predictive in vitro tools for the identification of substances corrosive to the skin has opened up the practical possibility of carrying out safe and ethical studies on small panels of humans. The human 4‐h patch test has been developed to meet the needs of identifying chemical skin irritation potential, providing data which is inherently superior to that given by a surrogate model, such as the rabbit. This paper reviews in detail the present state of the human 4‐h patch test, highlighting its advantages and noting its utility as the ‘gold standard’ on which to build future in vitro models.
Safety, efficacy and provenance of tea tree (Melaleuca alternifolia) oil
Authors: Carson C. F. , Riley T. V.
Published: March 2003

The identity, sources and composition of tea tree (Melaleuca alternifolia) oil are discussed, and earlier errors in the literature indicated. Reports of both therapeutic and allergenic effects are reviewed.
Clinical allergy to cocamidopropyl betaine: reactivity to cocamidopropylamine and lack of reactivity to 3‐dimethylaminopropylamine
Authors: McFadden John P. , Ross Janet S. , White Ian R. , Basketter David A.
Published: March 2003

7 patients allergic to cocamidopropyl betaine (CAPB) were detected by positive patch test reactions to Tegobetaine L7TM. These patients were then asked to participate in further testing to its potential impurities, cocamidopropylamine and 3‐dimethylaminopropylamine (DMAPA). 4 of the 7 patients were tested to purified CAPB and cocamidopropylamine, with 2 reacting to the purified betaine on allergy patch testing and 3 reacting to cocamidopropylamine 0.1%. At another date, 6 of the 7 were successfully recalled for testing to DMAPA in the presence of sodium lauryl sulfate (SLS) or pure CAPB; 1/6 reacted to DMAPA in water, but only at very high concentrations, at least 3 orders of magnitude higher than that to which skin exposure would occur from use of products containing CAPB. Both SLS and CAPB increased the number of reactions recorded to high levels of DMAPA. However, positive reactions to much lower concentrations of DMAPA (100 ppm) were found in only 1/6 subjects and then only in the presence of the irritant SLS. 0/6 reacted to pure CAPB alone. Taken together, these results suggest that DMAPA is unlikely to be an important contact allergen in CAPB of appropriate quality. They also confirm that CAPB of suitable purity, where levels of both cocamidopropylamine and DMAPA are minimized, is unlikely to trigger reactions in those ostensibly allergic to the material.
Allergic contact dermatitis from sodium dihydroxycetyl phosphate, a new cosmetic allergen?
Authors: Lomholt Hans , Rastogi Suresh C. , Andersen Klaus. E.
Published: March 2003

Sodium dihydroxycetyl phosphate (trade name Dragophos S 2/918501) was identified as a contact allergen in a herbal moisturizing cream causing severe acute contact dermatitis on the hands and face of a 41‐year‐old woman. Sodium dihydroxycetyl phosphate is a complex mixture of phosphate esters of dihydroxycetyl alcohol, and subsequent analysis and testing revealed hexadecane‐1,2‐diol as 1 of the allergenic ingredients. Another possible allergen in the compound appears to be hexadecane‐1,2‐diol, 2‐isopropyl ether.
Fragrance chemicals in domestic and occupational products
Authors: Rastogi S. C. , Heydorn S. , Johansen J. D. , Basketter D. A.
Published: March 2003

Epidemiological studies have described an increasing prevalence of fragrance allergy and indicated an association with hand eczema. 59 domestic and occupational products intended for hand exposure were subjected to gas chromatography‐mass spectrometric (GC‐MS) analyses to test the hypothesis that fragrance chemicals known to have the potential to cause contact allergy but not included in fragrance mix (FM) may be common ingredients in these products. A quantitative analysis of 19 selected fragrances was performed by GC‐MS. Further analysis of GC‐MS data revealed the presence of 43 other fragrance chemicals/groups of fragrance chemicals in the products investigated. Among the 19 target substances the most commonly detected were limonene in 78%, linalool in 61% and citronellol in 47% of the products investigated. The FM ingredients were present in these products with the following frequencies: oak moss (evernic acid methylester) 2%, cinnamic alcohol 2%, cinnamic aldehyde (cinnamal) 3%, isoeugenol 5%, α‐amylcinnamic aldehyde (amyl cinnamal) 8%, hydroxycitronellal 12%, eugenol 27%, and geraniol 41%. Thus, the chemical analyses of domestic and occupational products indicates that investigation of potential contact allergy related to these products types should consider fragrance allergens additional to those in the FM, since these may occur with high frequency.
Factors affecting thresholds in allergic contact dermatitis: safety and regulatory considerations
Authors: Basketter David A. , Evans Peter , Gerberick G. Frank , Kimber I. A. N.
Published: March 2003

Although it is now well understood that thresholds exist for both the induction and the elicitation of allergic responses, such as those of allergic contact dermatitis, it must also be appreciated that for any given allergen, these thresholds are not absolute values. They will vary between individuals, and according to the conditions of exposure to the allergen. Therefore, it is necessary for the purposes both of risk assessment and regulatory toxicology to appreciate the variables involved and to adopt strategies that incorporate this understanding. In this short article, the nature of thresholds in allergic contact dermatitis and the factors affecting them are reviewed. In particular, thresholds will vary according to whether skin exposure is transient or prolonged, open or occluded and single or repeated. The condition of the skin, the presence of inflammation and the matrix in which a chemical sensitizer comes into contact with the skin also are important. However, the scale of these variables frequently is quantifiable. Thus, recommendations can be made concerning how these considerations can be embraced by those responsible for safety evaluation and for the shaping of regulations for skin sensitizing chemicals/formulations.
Efficacy of stratum corneum lipid supplementation on human skin
Authors: Coderch L. , De Pera M. , Fonollosa J. , De La Maza A. , Parra J.
Published: March 2003

Recent studies suggest that supplementing intercellular lipids of the stratum corneum in ageing populations or in people with dry skin can stimulate the functioning of the skin. This work lends support to the reinforcement capacity of two different stratum corneum lipid mixtures (synthetic stratum corneum lipid mixtures, SSCL, and internal wool lipid extracts, IWL) formulated as liposomes on healthy skin of two differently aged groups of individuals. Protection of healthy skin against detergent‐induced dermatitis was evaluated. Transepidermal water loss and capacitance were used to evaluate the effect of these formulations in in vivo long‐term studies. Increase in water‐holding capacity is obtained only when the formulations applied are structured as liposomes. This is slightly more pronounced for aged skin. Subsequent SLS exposure reflected the protection of healthy human skin against detergent‐induced dermatitis. Slightly better results were obtained with IWL containing a mixture of natural ceramides than with SSCL with only one ceramide present in the formulation. All these results support the beneficial effects of skin lipid supplementation given their resemblance to the lipids in the stratum corneum both in composition and in the structuring of the formulation.
The local lymph node assay: past, present and future
Authors: Kimber Ian , Dearman R. J. , Basketter D. A. , Ryan C. A. , Gerberick G. F.
Published: March 2003

The local lymph node assay (LLNA) was developed originally as a method for the identification of chemicals that have the potential to cause skin sensitization and allergic contact dermatitis. The assay is based on an understanding that the acquisition of contact sensitization is associated with, and dependent upon, the stimulation by chemical allergens of lymphocyte proliferative responses in skin‐draining lymph nodes. Those chemicals that provoke a defined level of lymph node cell (LNC) proliferation (a 3‐fold or greater increase compared with concurrent vehicle controls) are classified as skin sensitizers. Following its original inception and development, the LLNA was the subject of both national and international interlaboratory collaborative trials, and of very detailed comparisons with other test methods and with human skin sensitization data. The assay has now been validated fully as a stand‐alone test for the purposes of hazard identification. In recent years, there has been a growing interest also in the use of the LLNA to assess the potency of contact allergens and in risk assessment. There is reason to believe that the extent of skin sensitization achieved is associated with the vigour of LNC proliferation induced in draining nodes. Given this relationship, the relative potency of skin sensitizing chemicals is measured in the LLNA by derivation of an EC3 value, this being the concentration of chemical required to provoke a 3‐fold increase in the proliferation of LNC compared with controls. Experience to date indicates that relative potency as determined using this approach correlates closely with what is known of the activity of skin sensitizing chemicals in humans. In this article, we review the development, evaluation and validation of the LLNA for the purposes of hazard identification, and the more recent application of the method for evaluation of potency in the context of risk assessment. In addition, we consider what new applications and modifications are currently being investigated.
A clinical and patch test study of adult widespread eczema
Authors: Li Lin‐Feng , Wang Jing
Published: March 2003

The purpose of this study was to investigate the role of contact hypersensitivity (CHS) in adult widespread eczema (WE) and to analyse the aetiology of WE. 108 consecutive adult WE patients were patch tested. 352 patients with suspected localized allergic contact dermatitis (ACD) tested in the same period served as a control. The average age of the patients with WE was significantly greater than the control group (47.6 ± 15.0 v 39.2 ± 14.9, p < 0.01, Student's t‐test). More male patients were found in the WE group (42.6% vs 25.0%, p < 0.01, χ2‐test). 71 (65.7%) of the WE patients were patch test positive. ACD was diagnosed in 29 out of 108 (26.9% of the WE patients and 40.8% of the PT positive patients) WE patients. ACD was also suspected in another 42 patients (39.8%), who had at least 1 positive PT result but the relevance of PT was hard to determine. In the remaining 37 patch test negative patients, 2 cases of food allergy were diagnosed by clinical findings and open food challenge test. 1 case of atopic dermatitis was diagnosed. 34 patients (31.5%) were diagnosed as unclassified endogenous eczema. Most of the WE patients with ACD (15/29, 51.7%) were ACD from widespread contact with hair dye during bathing. Most of the WE patients with hair dye ACD were male (male : female = 2.75). The total positive rates of PT in the WE group were no different to the control (65.7% vs 61.5%, p > 0.05, χ2‐test). No significant difference was found for the positive rates of common contact allergens. The rate of atopy was no different between the 2 groups either (6.5% v 5.1%, p > 0.01, χ2‐test). These results indicated that contact sensitization was very common in adult WE. Neglected widespread contact with contact allergens, especially hair dye, plays a very important role in our adult WE. The roles of age and sex in WE need to be studied further.
A direct in vivo measurement of the three‐dimensional orientation of the occlusal plane and of the sagittal discrepancy of the jaws
Authors: Ferrario Virgilio F. , Sforza Chiarella , Serrao Graziano , Ciusa Veronica
Published: March 2003

The aim of the present investigation was to three dimensionally assess craniofacial relationships in vivo. Specifically, by using a non‐invasive direct technique, the following measurements were made: 1) natural head position relative to the ground; 2) orientation of the occlusal plane relative to the subject's intrinsic facial planes; and 3) anteroposterior discrepancy of the dental bases, taking into consideration all the facial hard‐ and soft‐tissue structures. Several dental and soft‐tissue facial landmarks were directly digitized from 24 adult healthy volunteers with Angle Class I occlusions by means of an electromagnetic three‐dimensional computerized digitizer. In natural head position, the three‐dimensional orientation of Camper's, occlusal, and mandibular planes were measured along with the anteroposterior maxillo‐mandibular discrepancies. In the frontal plane projection, all the measured planes appeared about horizontal. In the lateral plane projection, on average, Camper's plane deviated from the true horizontal by approximately 18° (in a ‘head flexed’ direction). The occlusal plane deviated from the same horizontal by about 14°, while the mandibular plane had a steeper inclination (about 30°); both planes were significantly correlated to Camper's plane. The measurements of anteroposterior jaw discrepancy revealed a wide range of sagittal relationships in the analyzed subjects. The method was found to be repeatable and fast. This direct three‐dimensional in vivo assessment of the orientation of occlusal plane relative to the other facial planes could allow for a more comprehensive analysis of maxillo‐mandibular sagittal discrepancies.
Expression of desmoglein I and plakoglobin in skin carcinomas
Authors: Tada Hideyuki , Hatoko Mitsuo , Tanaka Aya , Kuwahara Masamitsu , Muramatsu Tsutomu
Published: March 2003

Reduction or absence of cell‐cell adhesion molecules has been reported in various carinomas and the abnormal expression of these molecules contributes to the invasive and metastatic behavior of malignant tumor cells. In epidermal keratinocytes, the main cell‐cell adhesion systems are adherens junctions and desmosomes. Previous studies have shown that, in skin carcinomas, the decreased expression of E‐cadherin, major constitutional glycoprotein of adherens junctions, is associated with the invasive and metastatic ability of the tumor cells. In the present study, we examined the expression of desmoglein I and plakoglobin, the constitutional components of desmosomes, in various skin carcinomas such as basal cell carcinoma (BCC), squamous cell carcinoma (SCC), extramammary Paget's disease and Bowen's disease by an immunofluorescence method. In normal human skin, desmoglein I and plakoglobin were strongly expressed in the intercellular space of the epidermis except for the basal cell layer. In BCC and SCC, the expression of desmoglein I and plakoglobin was markedly reduced or absent in tumor cells. In carcinoma in situ of Paget's disease, compared with the normal epidermal cells surrounding tumor cell nests, the expression of these molecules was reduced in tumor cells. In Paget's disease with dermal infiltration of tumor cells, the expression of these molecules was almost absent throughout the epidermis. In Bowen's disease, the expression of desmoglein I was reduced in the clumping cells and dyskeratotic cells. These results suggest that the expression of desmosomal cadherin is reduced or absent in human skin carcinomas, and that reduction of these molecules may also contribute to the invasiveness and metastasis of skin carcinomas.
Extranodal peripheral T‐cell lymphoma with angiocentric growth pattern and Epstein‐Barr viral DNA associated affecting paratesticular soft tissue
Authors: Pérez‐Vallés Ana , Sabater‐Marco Vicente , Carpio‐Máñez Dominica , Botella‐Estrada Rafael , Nogueira‐Vázquez Enrique , Martorell‐Cebollada Miguel
Published: March 2003

Peripheral T‐cell lymphomas are uncommon, accounting for only 10% to 15% of all non‐Hodgkin lymphomas and their classification has been controversial. We report a case of peripheral T‐cell lymphoma with angiocentric growth pattern which presented as a paratesticular tumoral nodule in a 47‐year‐old‐man. Formalin‐fixed paraffin‐embedded samples from the paratesticular tumor and non‐infiltrated adjacent tissue were submitted to histological, immunohistochemical, polymerase chain reaction (PCR)‐based and in situ hybridization analysis. Histopathologically, there was a lymphomatous infiltrate in the paratesticular soft tissue, composed of a variable mixture of medium‐sized to large cells with large cytoplasm and irregular‐shaped nuclei, together with blood vessel destruction, necrosis and karyorrhexis. Immunohistochemical study revealed a high p53 expression in neoplastic cells that showed T cytotoxic immunophenotype, failing to express the natural killer (NK)‐cell antigen CD56. A monoclonal rearrangement of the T‐cell receptor (TCR) γ gene by a PCR technique was demonstrated. Type‐A Epstein‐Barr Virus (EBV) DNA was detected by PCR‐based analysis. A combined in situ hybridization and immunohistochemical study revealed that most cells labeled positive for EBV RNA showed immunostaining with the CD45RO antibody. Based on the above results, the case reported was classified as extranodal peripheral T‐cell lymphoma with cytotoxic phenotype and EBV associated. The present case does not fit neatly into any of the specific types of peripheral T‐cell lymphomas of the REAL classification, so a diagnosis of peripheral T‐cell lymphoma unspecified was made.
An immunohistopathologic study in cutaneous necrotizing vasculitis
Authors: Bielsa I. , Carrascosa J. M. , Hausmann G. , Ferrándiz C.
Published: March 2003

In order to investigate the importance of timing in the immunophenotypical characteristics of the inflammatory infiltrate and in the adhesion molecules expression in cutaneous necrotizing vasculitis (CNV) we carried on an immunohistopathologic study. An avidin‐biotin‐streptavidin peroxidase technique was performed on 21 lesional skin biopsy specimens obtained sequentially at 0 to 24, 72 and 120 hours from seven patients with a CNV presenting as palpable purpura. A panel of monoclonal antibodies specific for inflammatory cells (T lymphocytes, polymorphonuclear leukocytes, macrophages, dendritic cells) and different adhesion molecules (E‐selectin, ICAM‐1, VCAM‐1, LFA‐1, VLA‐4) was used. Moreover, HECA‐450 monoclonal antibody was used to identify cutaneous lymphocyte antigen (CLA) in the inflammatory infiltrate. In all cases, polymorphonuclear leukocytes predominated in the early phase of CNV and their number decreased significantly with time (p=0.0001). The T lymphocytes were present from the beginning and their number remained stable or increased slightly in time (p=0.1), thus becoming predominant in the perivascular infiltrate in older lesions. Macrophages were scattered on interstitium since the early phase and they showed a time‐dependent increase (p=0.0003). E‐selectin (ELAM‐1) expression was detected at the first biopsy and it decreased depending on the age of the evolving vasculitis (p=0.0033). The expression of CLA decreased also with time in 5 of the 7 cases (p=0.0001). Our study supports the existence of an unique histopathologic pattern in CNV, in which the inflammatory infiltrate varies with time at the expense of the number of polymorphonuclear cells and macrophages.
Expression of the intermediate filament peripherin in extraskeletal myxoid chondrosarcoma
Authors: Cummings Thomas J. , Shea Christopher R. , Reed Jon A. , Burchette James L. , Prieto Victor G.
Published: March 2003

The embryologic histogenesis of cartilage is not well characterized. While cranial cartilage is believed to be derived from pluripotential precursor cells of the neural crest, chondrocytes found elsewhere in the body are thought to be derived from mesoderm. As such, soft tissue tumors with cartilaginous differentiation may be related to neural crest or mesoderm. Peripherin is an intermediate filament encoded on chromosome 12, involved in growth and development of the peripheral nervous system. Peripherin is apparently expressed exclusively in cells derived from the neural crest and neural tube. A group of six soft tissue tumor types was selected because they are either of controversial differentiation or cytogenetically related to chromosome 12. A total of 41 cases was evaluated with antibodies against the intermediate filament peripherin. A panel of neural and neuroendocrine differentiation markers was used in selected cases. Three of five extraskeletal myxoid chondrosarcomas showed strong cytoplasmic reactivity with anti‐peripherin. No peripherin expression was noted in any of eleven epithelioid sarcomas, eight liposarcomas, seven conventional chondrosarcomas, four neurothekeomas, three alveolar soft part sarcomas, or three clear cell sarcomas. The finding of peripherin expression in some extraskeletal myxoid chondrosarcomas may suggest the ability of some tumors to demonstrate both neural and chondroid differentiation.
Immunohistochemical evaluation of basal cell carcinoma and trichepithelioma using Bcl‐2, Ki67, PCNA and P53
Authors: Abdelsayed Rafik A. , Guijarro‐Rojas Mercedes , Ibrahim Nabil A. , Sangueza Omar P.
Published: March 2003

Most basal cell neoplasms with follicular differentiation represent a heterogenous group of tumors. Although may arise anywhere in the skin, these neoplasms commonly occur on the head and neck regions. The majority of these neoplasms are basal cell carcinomas (BCC) and trichoepitheliomas (TE). Overlapping histopathologic features between these benign and malignant tumors are occasionally seen which may create problems in rendering a definitive diagnosis. The intent of this investigation was two‐fold: 1) to examine whether there are quantitative differences of the cellular expression of Bcl‐2, Ki67, PCNA and P53 between BCC and TE; and 2) to examine the value of these immunostains in differentiating between BCC and TE. Twenty cases of BCC were stained with antibodies for Bcl‐2, Ki67, PCNA and P53. The positive cell indices and staining characteristic of these immunostains were compared with those of 20 cases of TE. The cell indices for each group were analyzed statistically utilizing the analysis of variance (ANOVA) technique. Intensity and patterns of Bcl‐2 and P53 expression were similar between BCC and TE. The ANOVA analysis showed no statistically significant differences between cell indices for cases stained with antibodies for Bcl‐2 and P53 (p=0.49 and p=0.87 respectively) in the two neoplastic groups. There were intense labelling and generalized patterns of Ki67 and PCNA expression in BCC. Conversly, Ki67‐ and PCNA‐labelled cells were much fewer in TEs than those noted in BCCs. Additionally, Ki67‐ and PCNA‐positive cells were limited to the peripheral layers of the neoplastic islands of TEs. There were statistically significant differences between cell indices for cases stained with antibodies for Ki67 and PCNA (p=0.02 and p=0.05 respectively) in the two neoplastic groups. BCC and TE exhibited comparable expressions of Bcl‐2 and P53 with similar intensity of labelling and patterns of distribution. This suggests possible similar mechanisms of growth regulation in both neoplasms. However, Ki67 and PCNA labelling was noted with significantly increased numbers and recognizably different patterns in BCCs compared to TEs. This may help explain the significant capabilities in tumor proliferation and the aggressive behavior of BCC compared to the limited growth potential of TE. Additionally, Ki67 and PCNA staining intensity and charactristics may have some value in differentiating between BCC and TE.
Epithelioid sarcoma arising on the nose of a child: a case report and review of the literature
Authors: Billings Steven D. , Hood Antoinette F.
Published: March 2003

A 4‐year‐old boy presented with a 6‐month history of a red papule on the nasal septum. Physical examination was otherwise unremarkable. A biopsy specimen showed an epithelioid sarcoma characterized by nodular collections of epithelioid tumor cells with central, tumor cell necrosis. By immunohistochemistry the tumor cells were positive for cytokeratin, epithelial membrane antigen, vimentin, and CD34, but negative for S‐100, CD31, factor VIII‐related antigen, CD68, actin, desmin and myoglobin. Epithelioid sarcoma is an uncommon tumor of uncertain histogenesis that typically arises in the extremities of young adults. Both the age of our patient and the location of his tumor are unusual, emphasizing the spectrum of presentations that may occur with epithelioid sarcoma. Epithelioid sarcoma should be considered in the differential diagnosis of granulomatous diseases and epithelioid tumors of children, even in unusual locations.
Detection of TCR‐γ gene rearrangements in early mycosis fungoides by non‐radioactive PCR‐SSCP
Authors: Murphy Michael , Signoretti Sabina , Kadin Marshall E. , Loda Massimo
Published: March 2003

Early mycosis fungoides (MF) can mimic numerous benign inflammatory dermatoses on routine histological examination. In this study, a recently developed non‐radioactive polymerase chain reaction‐single strand conformational polymorphism (PCR‐SSCP) technique was used to assess T‐cell clonality in paraffin‐embedded skin biopsies clinically and pathologically suspicious for early MF. Non‐radioactive PCR‐SSCP is a simple, sensitive, reproducible and rapid procedure requiring minimal instrumentation. DNA was extracted from 22 skin biopsies of 20 patients with suspected patch stage MF and 15 skin biopsies of inflammatory dermatoses. Vγ1–8, Vγ9, Vγ10, Vγ11 and Jγ1/Jγ2 consensus primers were used for T‐cell receptor (TCR)‐γ gene rearrangement amplification. PCR products were analyzed by non‐radioactive SSCP. Clonal TCR‐γ gene rearrangements were detected in 17 of 22 (77%) suspected MF specimens. Clonal SSCP banding patterns were different among individual patients. In addition, identical banded patterns were demonstrated in serial skin biopsies from the same patient. No dominant T‐cell clones were found in the inflammatory dermatoses studied. Therefore, non‐radioactive PCR‐SSCP is a useful molecular diagnostic tool for assessment of T‐cell clonality in paraffin‐embedded specimens suspicious for early MF. The SSCP imprint of PCR products is specific for each TCR‐γ gene rearrangement, and may be used to evaluate concurrent/recurrent disease in individual patients.
The carcinoembryonic antigen (CEA) family (CD66) expressed in melanocytic naevi is not expressed in blue naevuscell naevi in dendritic type
Authors: Egawa Kiyofumi , Honda Yumi , Kuroki Masahide , Ono Tomomichi
Published: March 2003

Background: Although sporadic reports have regarded the expression of the carcinoembryonic antigen (CEA) family in melanoma, there has been no information about the expression in precursor lesions of melanoma such as melanocytic naevi and blue naevi.

Methods: The expression was immunohistochemically studied in frozen biopsy specimens of 45 acquired and 16 congenital melanocytic naevi and 20 blue naevi, using a panel of monoclonal and polyclonal antibodies that recognize different epitopes of CEA and related molecules.

Results: Members of the CEA glycoprotein family were strongly expressed in all of the subtypes of melanocytic naevus. A reduced expression of the CEA glycoproteins with increased dermal depth or acquisition of a spindled morphology of naevus cells was apparent. The expression was not seen in the present blue naevi and normal epidermal melanocytes.

Conclusions: Although the significance of the expression was not clarified, this report has clearly demonstrated that the CEA family is strongly expressed in melanocytic naevi and immunoreactivity is divergent between melanocytic naevi and blue naevi and between dermal naevus cell types, suggesting that the expression may be altered with architectual changes in the melanocyte‐lineage cells.
The histologic value of adnexal (eccrine gland and follicle) infiltration in mycosis fungoides
Authors: Rongioletti F. , Smoller B.
Published: March 2003

Background: To verify the incidence and the possible diagnostic use of detecting adnexotropism in mycosis fungoides (MF).

Methods: We reviewed the frequency and the intensity of the eccrine and follicular infiltration in 104 biopsy specimens from indisputable cases of MF and in a control group of 20 biopsy specimens of spongiotic dermatitis. Syringohyperplasia and follicular mucinosis were also evaluated.

Results: A prominent eccrine infiltration was noted in 32 of 104 specimens (30%). Marked acrosyringial and ductal eccrine hyperplasia was present in 5 specimens (5%). In 13 of the 32 specimens with prominent eccrine infiltration (40%), epidermotropism was slight or less evident than syringotropism. Follicular structures were visible in 59 specimens and significantly infiltrated in 57%. Follicular mucinosis was found in 5 (8.4%). In the control group of spongiotic dermatitis, a significant eccrine and follicular infiltration was found only in 1 case (5%).

Conclusions: Adnexal (eccrine gland and follicle) infiltration may be a useful diagnostic tool in MF, particularly in those in which epidermotropism is slight.
Interleukin 4 and interferon‐γ expression of the dermal infiltrate in patients with erythroderma and mycosis fungoides. An immuno‐histochemical study
Authors: Sigurdsson Vigfús , Toonstra Johan , Bihari Ilse C. , Bruijnzeel‐Koomen Carla A. F. M. , Van Vloten Willem A. , Thepen Theo
Published: March 2003

Background: Erythroderma, or generalized erythema of the skin, may result from different causes. At present it is unclear whether the underlying patho‐mechanisms that lead to erythroderma are identical or different depending on the original disease. The aim of this study was to investigate the dermal cytokine profile in different types of erythroderma and mycosis fungoides.

Methods: Snap‐frozen skin biopsy specimens from 33 patients with erythroderma were studied. Thirteen had idiopathic erythroderma, 7 erythrodermic atopic dermatitis, 5 Sézary syndrome and 8 had erythroderma from miscellaneous causes. We also studied 6 patients with mycosis fungoides (5 plaques and 1 tumor) and 5 healthy non‐atopic volunteers. The biopsies were immunohistochemically stained for interleukin 4 (IL‐4) and interferon γ (IFN‐γ). All positive cells for IL‐4 and IFN‐γ in the dermis were counted and the number of positive cells was calculated per mm2. IL‐4/IFN‐γ ratio was calculated for each biopsy.

Results: The patients with idiopathic erythroderma, atopic dermatitis and miscellaneous erythroderma, all showed more IFN‐γ‐positive cells than IL‐4‐positive cells in the dermis. The median IL‐4/IFN‐γ ratio for these three groups was 0.6, 0.9 and 0.45, respectively. These differences were not statistically significant. All patients with Sézary syndrome however, showed more IL‐4‐positive cells than IFN‐γ‐positive cells. The median IL‐4/IFN‐γ ratio was 1.8, which is significantly higher than in the other groups (p<0.05). In mycosis fungoides roughly the same number of cells expressed IL‐4 and IFN‐γ. The median IL‐4/IFN‐γ ratio was 1.0, which is significantly lower than in Sézary syndrome (p<0.05).

Conclusions: The dermal infiltrate in patients with Sézary syndrome mainly shows a T‐helper 2 (Th2) cytokine profile, this in contrast to T‐helper 1 (Th1) cytokine profile in benign reactive erythroderma. This indicates that although a relative uniform clinical picture of erythroderma is obvious, a different patho‐mechanisms may be underlying.
Immunohistochemical expression of cyclooxygenase‐2 in skin cancers
Authors: Kagoura Masayori , Toyoda Masahiko , Matsui Chihiro , Morohashi Masaaki
Published: March 2003

Background: Cyclooxygenase (COX), also known as prostaglandin endoperoxide synthase, catalyses the conversion of arachidonic acid to prostanoids. There are two different isoforms of COX, referred to as COX‐1 and COX‐2. Overexpression of COX‐2 has been demonstrated in various neoplasms, such as experimentally promoted tumors, gastrointestinal cancers and breast tumors.

Methods: In this study, we used immunohistochemistry to investigate COX‐2 expression in a series of basal cell epitheliomas (BCE), Bowen’s disease, squamous cell carcinomas (SCC) and metastatic tumors of the skin.

Results: Four of 16 BCE showed a positive reaction for COX‐2 and the adenoid type of BCE was the most strongly positive. In Bowen’s disease, the extent of positive staining for COX‐2 was even higher than that in BCE. Eleven of 15 SCC showed a positive reaction for COX‐2 and the pattern of staining was heterogeneous with more intense staining in the center of the tumor nests. In metastatic tumors, the percentage of COX‐2‐positive tumor cells and the intensity of their staining was low compared with Bowen’s disease and SCC.

Conclusions: These results indicate that the intensity of COX‐2 staining and its heterogeneous distribution are related to the degree of cellular differentiation and the various phenotypes of tumor cells, but the extent of COX‐2 staining did not correlate with the degree of malignancy.
Metastatic adenocarcinoma of the esophagus to the skin: new patterns of tumor recurrence and alternate treatments for palliation
Authors: Smith Kathleen J. , Williams John , Skelton Henry
Published: March 2003

Background: Esophageal cancer, particularly adenocarcinoma of the esophagus (ACE), has been steadily increasing in incidence in the United States. In the past, patients usually died rapidly with locoregional disease that leads to inanition and aspiration. However, today when patients with ACE are treated successfully with induction chemotherapy and radiation therapy, followed by surgical excision, ACE usually does not recur locally, but presents with metatastic disease. We present a 62‐year‐old white male with ACE, which was treated with induction chemotherapy and radiation therapy followed by surgical excision. After approximately 1 year with no evidence of locoregional recurrence, the patient presented with diffuse cutaneous metastatic disease.

Methods: In addition to routine staining immunohistochemical stains for CK(AE1/AE3), CK7, CK 20, EMA, α‐smooth muscle (SM) actin, S‐100 protein, CD34, P53, Bcl‐2, c‐erbB‐2 were performed.

Results: The immunohistochemical profile was consistent with an esophageal origin showing positive staining with CK20 and CK7 as well as AE1/AE3 and EMA. In addition, there was marked nuclear expression of p53, as well as membrane expression of c‐erb‐B2; consistent with progression of the disease and poor response to further cytotoxic therapeutic regimes.

Conclusions: With new therapeutic protocols, we can expect to see more metastatic disease with recurrences of ACE. The histopathologic features and the immunohistochemical profile of the recurrent tumors may be helpful in determining alternate forms of therapy that either alone or in combination could be useful in palliation and delaying progression.()
Loss of tuberin, the tuberous‐sclerosis‐complex‐2 gene product is associated with angiogenesis
Authors: Nguyen‐Vu Phuong‐Anh , Fackler Ingrid , Rust Adelheid , DeClue Jeffrey E. , Sander Christian A. , Volkenandt Matthias , Flaig Michael , Yeung Raymond S. , Wienecke Ralf
Published: March 2003

Background: Tuberous sclerosis complex (TSC) is an autosomal dominantly inherited disorder associated with an alteration of the TSC2 tumor suppressor gene which encodes for the protein product tuberin. The disease is characterized by the development of hamartomas, e.g. cutaneous angiofibromas which consist of vascular cells, interstitial cells, and normal components of the skin. The Eker rat model, an animal model of inherited cancer, has been shown to carry a mutation of TSC2.

Methods: Immunohistochemical analyses of human angiofibromas were performed using antibodies directed against tuberin and angiogenic growth factors. Proliferation of human dermal microvascular endothelial cells (HDMEC) was determined after incubation with the supernatants of TSC2 (+/+) and TSC2 (−/−) rat embryonic fibroblasts (REF) that were derived from the Eker strain.

Results: Loss of the expression of tuberin was observed in the interstitial cells of 13 of 39 angiofibromas. The expression of tuberin was retained in the vascular cells. In all analyzed angiofibromas, the angiogenic factors bFGF, PD‐ECGF, VEGF and angiogenin were detected in the interstitial cells and/or vascular cells. Expression of PDGF‐B and TGF‐β1 was weak. Tissue culture supernatants from TSC2 (−/−) REF stimulated the growth of HDMEC significantly more than supernatants from TSC2 (+/+) REF.

Conclusion: A functional loss of tuberin may stimulate vascular growth.