Platinum(iv) N-heterocyclic carbene complexes: their synthesis, characterisation and cytotoxic activity.

Platinum(ii) N-heterocyclic carbene complexes have been oxidized by bromine or iodobenzene dichloride to provide the fully characterised corresponding platinum(iv) NHC complexes. Antiproliferative activities of Pt(iv) NHC complexes were assayed against several cancer cell lines and the results were correlated with respect to their stability. Mechanistic investigations revealed that mitochondrial dysfunction and ROS production were associated with the cytotoxic process induced by these compounds.

Reflectance confocal microscopy for the diagnosis of vulvar naevi: six cases.

BACKGROUND AND OBJECTIVES: The differential diagnosis between vulvar naevi and melanoma is challenging. In vivo reflectance-mode confocal microscopy (RCM) is an emerging technique that allows non-invasive high-resolution imaging of the skin and mucosa. It has recently been used for the study of vulvar melanosis and melanoma, but it has not been so far employed for the diagnosis of genital naevi. The objective of this study is to evaluate RCM features of vulvar naevi and to compare them with dermoscopical and histopathological aspects. METHODS: Clinical, dermoscopical, in vivo RCM and histological features of six vulvar naevi were evaluated. RESULTS: The clinical and/or dermoscopical aspects were suspicious in all six cases. RCM showed a blue naevus, an atypical genital naevus, a junctional naevus and three compound naevi that were later confirmed by histological examination. In one compound naevus, RCM showed focal cytological atypia and architectural irregularity without clear features of malignancy, confirmed by histological examination. CONCLUSIONS: Reflectance-mode confocal microscopy can play a role in non-invasive diagnosis of vulvar naevi, but further broader studies are required to validate our observations.

[Vemurafenib-induced toxic epidermal necrolysis]. / Nécrolyse épidermique toxique au vemurafenib.

BACKGROUND: Herein we report the first case of toxic epidermal necrolysis (TEN) occurring with use of vemurafenib. PATIENTS AND METHODS: A 75-year-old female patient was being treated with vemurafenib for stage IV melanoma with BRAF V600E mutation. She suddenly presented fever, diffuse pruriginous maculopapular erythema, palpebral edema, palmar bulla, conjunctivitis, cheilitis and mucosal ulceration. The condition progressed towards detachment affecting 50% of the skin area. Cutaneous biopsy revealed lichenoid dermatosis, chiefly vesicular with numerous eosinophils. Direct immunofluorescence (IFD) was negative. Vemurafenib was the only drug to which the reaction was ascribable and we concluded on vemurafenib-induced TEN. DISCUSSION: To our knowledge, this is the first reported case of vemurafenib-induced TEN, but this adverse effect, although already described in the BRIM-3 study, appears rare in clinical practice. Other severe skin reactions have been described in the literature. These include a case of Stevens-Johnson syndrome in a female patient treated with vemurafenib and previously receiving ipilimumab. A more common occurrence is cutaneous reactions involving efflorescence of benign hyperkeratotic lesions, occasionally accompanied by authentic epidermal carcinoma or keratoacanthoma, and requiring regular dermatological monitoring of patients treated with vemurafenib. CONCLUSION: If maculopapular exanthema occurs under vemurafenib, continuation of this treatment should be reassessed since the risk of progression to a more serious condition such as TEN, as seen in the present case, cannot be ruled out.

[Blastic plasmacytoid dendritic cell neoplasm revealed by ecchymotic lesions on the face]. / Tumeur à cellules plasmocytoïdes dendritiques blastiques révélée par des lésions ecchymotiques du visage.

BACKGROUND: Cutaneous CD4+CD56+ malignant tumor proliferation was previously called "CD4/CD56 hematodermic neoplasm". However, the most recent studies have shown that the disease develops from plasmacytoid dendritic cells and the tumor has been renamed "Blastic Plasmacytoid Dendritic Cell Neoplasm" (BPDCN). It is an aggressive disease with a poor prognosis and behaves like acute leukemia in the short to moderate term. PATIENTS AND METHODS: A 65-year-old man with no particular history consulted for a left laterocervical lesion of ecchymotic aspect that had appeared one year earlier. Topical corticosteroid therapy had been unsuccessful. Examination of biopsies with lymphocyte typing enabled a diagnosis of BPDCN to be made. At the histopathological level, biopsy showed an infiltrate comprising medium to large cells. Immunohistochemical examination was remarkable for the absence of expression of markers of T- and B-cell lines. However, these tumor cells expressed CD4, CD56 and TCL1. Staging of the disease was normal. Treatment with chemotherapy was initiated in collaboration with a team of hematologists. Autologous bone marrow transplant was then performed. DISCUSSION: BPDCN is a rare malignant blood dyscrasia. It is distinguished by inaugural skin involvement, with systemic manifestations occurring much later. Histopathological examination of a skin biopsy with immunostaining establishes the diagnosis. In terms of phenotype, the tumor population is highly characteristic. The cells are negative for antigens of T- and B- cell lines. However, these cells express CD4, CD56 and TCL1, which are markers of plasmacytoid dendritic cells. The disease carries a poor prognosis and evolves in the short to middle term in the same way as acute leukemia. First-line treatment consists of the chemotherapy regimens used in aggressive lymphoma or acute leukemia. A bone marrow graft is sometimes performed at the time of initial relapse. Average survival is 12 months for chemotherapy alone and 30 months for transplant after first relapse. Early bone marrow transplantation has been shown to improve survival.

[Efficacy of acitretin in IgA pemphigus]. / Pemphigus à IgA: efficacité de l'acitrétine.

BACKGROUND: IgA pemphigus is a particular entity among autoimmune blistering intraepidermal diseases. IgA pemphigus is subdivided into two types: intraepidermal neutrophilic IgA dermatosis and subcorneal pustular dermatosis. PATIENTS AND METHODS: We report the case of an 82-year-old woman with intraepidermal neutrophilic IgA pemphigus associated with IgA gammopathy. The histopathological findings were unusual, with numerous large subcorneal pustules, a few pustules in the stratum spinosum, and basal IgA deposition. A favourable outcome was achieved with acitretin. DISCUSSION: This observation is significant in that it highlights the difficulty of classification of IgA pemphigus, which is currently based on clinical and histopathological findings. There is currently no therapeutic consensus attitude but simply a set of empirical data.

[Erosive pustular dermatosis of the legs: retrospective study of 16 cases]. / Dermatose érosive et pustuleuse de jambes : étude rétrospective de 16 cas.

BACKGROUND: Erosive pustular dermatosis of the leg (EPDL) is a chronic clinical entity comprising combined erosion, pustules and crusts on the legs. There is still some discussion of the independent existence of this condition in the absence of specific diagnostic criteria. The purpose of this study is to describe the clinical and laboratory characteristics of EPDL based on a series of patients presenting a clinical picture consistent with this diagnosis. PATIENTS AND METHODS: This retrospective study included all patients seen in our department between 2005 and 2009 presenting a clinical picture consistent with EPDL, in accordance with the initial description. We collated and carried out descriptive analysis of the clinical features and progression of the disease and of laboratory results (microbiology, immunology and vascular tests). RESULTS: In all of the 16 patients included (mean age: 81 years; sex ratio M/F: 0.2), lesions were consistently located in the middle third of the anterior aspect of the leg and associated with ochre dermatitis and skin atrophy; they were bilateral in 10 of the 16 patients. For the most part, laboratory tests were negative or inconclusive, with the exception of direct cutaneous immunofluorescence (DIF). DIF was performed in 14 patients and in three cases showed linear C3 deposits, thus confirming the diagnosis of pretibial bullous pemphigoid. In the 13 remaining cases, a diagnosis of idiopathic EPDL was made. Three of these 13 patients were either presenting or had previously presented squamous cell carcinoma of the leg. Topical corticosteroids were effective in 12 of these 13 cases (mean treatment duration: six months). Relapse was common (6/12). DISCUSSION: Our study demonstrates the need for skin biopsy with DIF for patients presenting a clinical picture evocative of EPDL, since the clinical presentation can be very similar to that of pretibial pemphigoid. Trophic disorders associated with venous stasis are common in EPDL, although they are difficult to interpret because of the high prevalence of this condition among the elderly. Mention must be made of associated marked sun damage, suggesting a possible relationship between EPDL and erosive pustular dermatosis of the scalp.

[Long-term survival and spontaneous tumor regression in stage IV melanoma: possible role of adrenalectomy and massive tumor antigen release]. / Survie prolongée et régression tumorale spontanée au cours d'un mélanome de stade IV: rôles possibles de la surrénalectomie et de la libération massive d'antigènes tumoraux.

BACKGROUND: Mean survival for stage IV melanoma patients is 6 to 8 months. Long-term survival is rare and spontaneous regression even more unusual. PATIENTS AND METHODS: A 46-year-old woman underwent amputation of the left thumb for subungual melanoma in 1997. In 2002, lobectomy was performed for a single pulmonary metastasis. In June 2006, a seemingly isolated adrenal metastasis was detected, and was rapidly complicated by acute abdominal symptoms due to metastatic rupture that required emergency adrenalectomy. During surgery, peritoneal metastases were observed macroscopically and confirmed histologically. One month later, then every six months until July 2009, clinical and laboratory tests, and in particular positron emission tomodensitometry (PET) scans, revealed no further tumoural lesions. No treatment was given. Screening for signs of autoimmunity revealed isolated appearances of anticardiolipin antibodies starting in June 2006. DISCUSSION: This rare case suggests the existence of specific factors resulting in tumour control. The favourable prognostic value of autoimmune signs has been discussed in stage III and IV melanoma. A number of studies have also suggested a link between prolonged survival and adrenalectomy for single and multiple adrenal metastases, with rare cases of complete regression of residual tumour following non-oncological surgery, as occurred in our patient. Other possible mechanisms include massive release of tumour antigens following metastatic rupture possibly resulting in massive stimulation of antitumour immune response, as suggested in certain animal models. Laboratory tests to validate these hypotheses have been indicated and could open up fresh therapeutic horizons.

O-phosphoserine content of intermediate filament subunits.

Purified subunits of intermediate filaments obtained from a variety of tissues and cell types contain O-phosphoserine and, in some cases, smaller amounts of O-phosphothreonine. The O-phosphoserine content was estimated by reaction of performic acid oxidized subunits with methylamine in NaOH. Decamin of BHK-21 and CHO fibroblasts contained about 1 mol/mol. Avian and mammalian desmin consists of two subunits, an acidic (alpha) subunit which contained 2 mol/mol and a more basic (beta) nonphosphorylated subunit. The principal (Mr approximately 60 000) subunit of squid brain neurofilaments contained 5 mol/mol. Most mouse and bovine keratin subunits contained 3--6 mol/mol, although certain bovine subunits of higher molecular weight contained none. The O-phosphoserine contents of keratin subunits purified from the viable and stratum corneum layers were the same. The O-phosphoserine was located in non-alpha-helical regions of the subunits which presumably project out from the alpha-helical wall of the intermediate filaments. Most subunits could be partially dephosphorylated in vitro with alkaline phosphatase. It was found that the capacity of such partially dephosphorylated subunits for assembly into native-type filaments in vitro was independent of their phosphate content.

Characterization of the keratin filament subunits unique to bovine snout epidermis.

Steinert [Biochem. J. (1975) 149, 39-48] reported that the alpha-keratin polypeptides (the subunits of the intracellular keratin filaments) of bovine hoof and snout epidermis are the same. We now demonstrate that this is not so: in addition to the seven polypeptides previously identified in hoof epidermis, snout epidermis also contains at least three other polypeptides of higher molecular weight. These unique polypeptides were isolated, purified and characterized. They are chemically and structurally very similar to the other polypeptides of bovine epidermis and readily polymerize in vitro with them to form native-type epidermal keratin filaments.