Localised pain following contact with liquids.
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Biomedical subjects
Publications and source records attributed to A Claudy.
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In 1994, a study of nickel release and allergic contact dermatitis from nickel-plated metals and stainless steels was published in this journal. It was shown that low-sulfur stainless steel grades like AISI 304, 316L or 430 (S < or = 0.007%) release less than 0.03 microgram/cm2/week of nickel in acid artificial sweat and elicit no reactions in patients already sensitized to nickel. In contrast, nickel-plated samples release around 100 micrograms/cm2/week of Ni and high-sulfur stainless steel (AISI 303-S approximately 0.3%) releases about 1.5 micrograms/cm2/week in this acid artificial sweat. Applied on patients sensitized to nickel, these metals elicit positive reactions in 96% and 14%, respectively, of the patients. The main conclusion was that low-sulfur stainless steels like AISI 304, 316L or 430, even when containing Ni, should not elicit nickel contact dermatitis, while metals having a mean corrosion resistance like a high-sulfur stainless steel (AISI 303) or nickel-plated steel should be avoided. The determining characteristic was in fact the corrosion resistance in chloride media, which, for stainless steels, is connected, among other factors, to the sulfur content. Thus, a question remained concerning the grades with an intermediate sulfur content, around 0.03%, which were not studied. They are the object of the study presented in this paper. 3 tests were performed: leaching experiments, dimethylglyoxime and HNO3 spot tests, and clinical patch tests; however, only stainless steels were tested: a low-sulfur AISI 304 and AISI 303 as references and 3 grades with a sulfur content around 0.03%: AISI 304L, AISI 304L added with Ca, AISI 304L+Cu. Leaching experiments showed that the 4 non-resulfurised grades released less than 0.5 microgram/cm2/week in acid sweat while the reulfurized AISI 303 released around or more than 0.5 microgram/cm2/week. This is explained by the poorer corrosion resistance of the resulfurized grade. Yet all these grades had the same reaction to the DMG test (negative result), which shows again its lack of sensitivity. In contrast, the HNO3 spot test distinguished AISI 303 from the non-resulfurized grades. Clinical patch tests again showed that some patients (4%) were intolerant to AISI 303, while none were intolerant to the other grades. Thus, this study confirms that non-resulfurized stainless steels (S < or = 0.03%) like Ni-containing 304 and 304L should not elicit Ni contact dermatitis, while the resulfurized grades (S > 0.1%) should be avoided.
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Nm23 is a gene with a putative metastasis-suppressor function, whose expression is inversely correlated with the metastatic potential of some solid malignancies. Because very few data exist concerning the role of nm23 in skin tumors, we studied the immunohistochemical expression of nm23 gene product in frozen sections of normal skin and of 104 cutaneous benign or malignant, epithelial and mesenchymal tumors. Nm23 was found expressed within basal cells of the epidermis and its appendages. All basal cell carcinomas showed diffuse immunoreactivity predominating within cells located at the periphery of tumor masses; in contrast, most squamous cell carcinomas, premalignant lesions and the benign epithelial lesions studied showed very weak, if any, immunoreactivity. Benign nevi and most malignant melanomas expressed nm23 immunoreactivity and the pattern observed was similar between primary and metastatic lesions. These results show that nm23 is differentially expressed in cutaneous tumors. It seems likely that the strong immunoreactivity of basal cell carcinomas, contrasting with the almost non-expression in squamous cell carcinomas, reflects the different metastatic potential of these two types of tumors. In melanomas, no direct correlation between the metastatic phenotype and nm23 expression could be detected. Our results suggest that the nm23 gene is involved in cutaneous carcinogenesis; its precise role deserves further study.
Ultraviolet radiation B (UVB) on the skin induces erythema, inflammation and modifications of the immune system. These changes have been reported after excessive short-term or long-term exposure to broad spectrum UVB. In this study, we examined the effects of local repetitive UVB irradiation of 311 nm wavelength on the skin of seven young volunteers. Skin biopsies were taken before and after UVB irradiation, and we immunohistochemically analyzed the expression of CD1a and HLA-DR antigens of Langerhans cells (LC), the possible infiltration of dermis/epidermis by CD11b macrophages, the modifications or the induction of intercellular adhesion molecule-1 (ICAM-1), E-selectin and vascular cell adhesion molecule-1 (VCAM-1) involved in the binding of leukocytes to the endothelial surface and the development of perivascular infiltrates of LFA-1+ mononuclear cells. We also determined the expression of substance P receptors (SPR) using biotinylated substance P (SPB). Exposure of UVB 311 nm induced a drastic reduction of CD1a+ cells and a moderate increase of HLA-DR+ dendritic cells in the epidermis without infiltration by CD11b macrophages. An increase of the binding of SPB to upper layer epidermal cells was noted in five of seven biopsies. In the dermis, vessel-associated ICAM-1 expression increased and an induction of E-selectin occurred on nearly 20 to 40% of endothelial cells, but VCAM-1 expression remained undetectable. The percentage of LFA-1+ cells did not change significantly after irradiation. These observations may be compatible with a selective role of UVB 311 nm on the skin immune response.
Squamous cell carcinomas (SCC) are the most frequent tumours complicating organ transplantation. Whereas most SCC can be successfully treated with conventional surgery, other lesions show an aggressive course with recurrence and metastases. We assessed the value of nuclear morphometry in detecting tumours with an ab initio potential for aggressive course. Nuclear perimeter, area, feret X and feret Y were calculated semi-automatically on an image analyzer on histological sections of 15 non-aggressive, 15 aggressive and 6 recurrent SCC developed in seven organ graft recipients. We found statistically significant differences for all the parameters studied between recurrent and initially aggressive SCC, and, to a lesser extent, between non-aggressive and aggressive SCC. These results suggest that some SCC have ab initio a potential for more aggressive evolution; morphometry can be a useful adjunct in order to better study these lesions.
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BACKGROUND AND DESIGN: In a series of patients treated at a university department of dermatology, we assessed the clinicopathologic features of external anogenital lesions in organ transplant recipients. For 6 years, 1002 recipients with various dermatologic problems underwent assessment for the presence of proliferative external anogenital lesions; these lesions were examined histologically and virologically for the presence of human papillomaviruses (HPV). RESULTS: Twenty-three patients (2.3%) presented with anogenital lesions, women being more often involved. Clinicopathologic examination revealed 18 anogenital warts, 3 cases of bowenoid papulosis, 1 giant condyloma, and 1 in situ carcinoma. Other viral coinfections were frequent. The lesions were extensive and refractory to treatment in 13 patients, but lesions in 7 were cured alter the immunosuppressive treatment was tapered of discontinued. Dysplastic changes were frequent on histologic examination. Twenty-one lesions contained HPV; 6 of 13 patients with HPV DNA in their lesions harbored oncogenic types that predominated in dysplastic lesions. In some patients, the same HPV types were detected within cutaneous and anogenital lesions, suggesting self-contamination. CONCLUSIONS: External anogenital lesions are more rare than cutaneous lesions in organ transplant recipients. These lesions may represent a marker of immunosuppression, especially when they are extensive. Their clinical aspect is often misleading; furthermore, because of the presence of dysplastic histologic aspects and oncogenic HPV types, they could be susceptible to malignant transformation, necessitating regular surveillance.
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Somatostatin (SOM) is a ubiquitous peptide which is responsible for the inhibition of numerous biological functions. SOM is described as an antiproliferative molecule and an inhibitor of exocrine or endocrine secretion from a variety of tissues, including pancreas, gastrointestinal tract, central and peripheral nervous system. Mediation of SOM effects can be indirect or direct, respectively, through other molecules or receptors on target cells. We have searched for the presence of SOM in the epidermis using immunofluorescence, confocal laser scanning microscopy, radioimmunoassay, and chromatography. Immunofluorescence and confocal laser scanning microscopy studies were performed using rabbit antiserum anti-SOM and mouse monoclonal antibody directed to CD1a Langerhans cell (LC) marker disclosed with fluorescein or tetramethylrhodamine isothiocyanate conjugates. SOM was extracted from whole skin or epidermal cell suspension or LC-enriched suspensions and analysed by radioimmunoassay. We used an antiserum which was reactive for the 6-11 portion of native SOM. Chromatographic columns were performed on extracts from whole skin. The epidermis was SOM immunoreactive. LC were immunoreactive for SOM and the staining was membranous. SOM was extracted from the whole skin at about 0.13 +/- 0.02 fmol/mg of tissue (mean +/- SEM). The SOM concentration in epidermal cell suspensions was 1.5 +/- 0.9 fmol/10(6) cells. Data obtained with LC-enriched suspensions showed large variations between donors. Extracts from skin showed one peak with an elution profile like that of 14 amino acid SOM. This study demonstrates that 14 amino acid SOM is expressed in normal human epidermis.
We report changes in the antigen recognition pattern of sera from two pemphigus foliaceus patients with a long-term follow-up. The patients' sera were analysed by immunoblotting using different antigenic sources: cultured human keratinocytes, bovine tongue epithelium and a recombinant protein corresponding to the C-terminal end of the 230-kDa bullous pemphigoid antigen. While initial serum samples reacted exclusively with the 160-kDa desmoglein 1, the later sera reacted both with desmoglein 1 and a 190-kDa antigen immunolocalized to the desmosomal plaque, previously demonstrated to be recognized by sera of some patients with paraneoplastic pemphigus. IgG subclass analysis further showed that antidesmoglein 1 antibodies were of IgG1 and/or IgG4 subclasses, while anti-190-kDa antibodies were IgG3. The patients were free of malignancy.
The stratum corneum (SC) has long been considered as a sort of inert membrane destined to be shed at the surface of the epidermis. During the last two decades, however, several lines of evidence have been reported, suggesting that active physical and chemical changes take place in the horny layer despite the absence of intracytoplasmic organelles. In particular, processing of filaggrin, replacement of the plasma membrane by a ceramide envelope and constant, progressive modification of extracellular lipid multilayers have been put forward. Recently, attention has focused on the intercellular junctions, which may be involved in the regulation of SC desquamation. Corneodesmosin, a newly discovered protein of s.c. desmosomes (corneodesmosomes), is synthesized at the latest stages of keratinocyte differentiation and persists between the horny cells until desquamation occurs. In the present study, we performed immunohistochemical and immuno-ultrastructural investigations on corneodesmosin expression in various skin lesions characterized by abnormal production and/or retention of the horny layer. Our results suggest that corneodesmosin expression is independent from profilaggrin synthesis. We found corneodesmosin in almost all morphologically recognizable corneodesmosomal structures and specifically those which persisted up to the SC surface. Hyperkeratotic lesions which are characterized by an increased number of junctions showed intense immunoreactivity with anticorneodesmosin antibody. A complete absence of corneodesmosin was not observed in any disease. This finding, together with our previous biochemical studies, suggests that corneodesmosin may exert a protective function against proteolytic degradation of corneodesmosomes both in normal skin and in the pathological horny layer.
Organ transplant recipients on immunosuppressive therapy are prone to skin cancers, especially squamous cell carcinomas developing on sun-exposed areas. Their frequency increases with time after transplantation reaching 40-70% of the patients after 20 years. Squamous cell carcinomas tend to be multiple and may have a life-threatening course. Most studies concern kidney transplant recipients but new data are now available on recipients of other organs. Carcinogenic factors include mainly immunosuppressive treatments, UV light and human papillomaviruses; the role of genetic factors is more equivocal. Melanomas and other rare tumors such as Merkel cell tumors or sarcomas are also increased. Surgical excision with histological examination represents the treatment of choice. When lesions become multiple and/or aggressive, additional therapeutic methods are necessary, such as topical or oral retinoids and in some cases, reduction of the immunosuppressive treatment. Radiotherapy should be reserved to limited cases. Prevention must be undertaken by a regular dermatological examination and sun protection.
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Substance P (SP) released by cutaneous C fibres is involved in the physiopathology of cutaneous lesions. As normal human keratinocytes have been reported to express SP receptors, we studied the effects of SP on keratinocyte activation markers such as ICAM-1 induction and cytokine production. Human keratinocytes derived from skin obtained during plastic surgery were cultured in defined medium (MCDB 153) and were stimulated by SP. Flow cytometry analysis showed that SP (10(-7) and 10(-5) M) as well as the specific NK1 agonist Sar9Met(O2)11SP (Sar Met) induced a slight but significant expression of ICAM-1 at the cell surface during treatment periods of 24 h and 48 h. SP (10(-5) M) also induced a significant but transient increase in the production of IL-1alpha, IL-1beta, IL-1 receptor antagonist and IL-8 which was detectable by ELISA techniques 6 h after stimulation. This elevation returned to constitutive levels 24 or 48 h postinduction. TNFalpha secretion was detected in stimulated cells only after 48 h. These results suggest that SP can activate keratinocytes and support its role in the local inflammatory reaction.
BACKGROUND: Linear IgA bullous dermatosis (LABD) is an autoimmune subepidermal blistering disease defined on the basis of direct immunofluorescence findings. CASE REPORT: An 18 month-old girl suffering from LABD was studied by indirect immunofluorescence on salt-split skin and by Western blot in an attempt to characterize the involved autoantigen. Direct immunofluorescence showed an exclusive linear IgA deposit at the dermal-epidermal junction. Indirect immunofluorescence revealed circulating autoantibodies that reacted with the epidermal side of salt-split skin; they reacted by Western blot with a 180 kDa epidermal antigen, as in bullous pemphigoid. CONCLUSION: This dermatosis fulfilling the clinical features and direct immunofluorescence criteria for childhood LABD seems to represent a case of IgA bullous pemphigoid. It further underscores the nosologic heterogeneity of LABD, which probably includes, apart from bullous pemphigoid, epidermolysis bullosa acquisita and cicatricial pemphigoid.
It has been recently suggested that soluble tumour necrosis factor receptors (sTNF-Rs) may represent prognostic factors in cancer. In malignant melanoma, the intercellular adhesion molecule (ICAM-1) has been described as involved in progression of the disease and is upregulated by TNF alpha. We report in this study the serum concentrations of sTNF-R1 and sTNF-R2 in 32 patients with primary melanoma and in 21 patients with metastatic melanoma, in correlation with those of soluble ICAM-1 (sICAM-1). Significantly raised sTNF-R1 levels were detected only in patients with metastatic melanoma compared with normal controls (P < 0.002), whereas sTNF-R2 levels were increased both in primary and metastatic melanoma (P < 0.001). The ratio of type 2 to type 1 proteins increased in malignant melanoma compared with the controls but remained constant with the progression of the disease. A correlation between sTNF-Rs and sICAM-1 concentrations in patients' sera was observed in metastatic melanoma. The combined adverse effects of these soluble proteins on normal immune effector functions may contribute to tumour progression.