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Biomedical subjects

F Aubin

Publications and source records attributed to F Aubin.

At least 37 records · Page 2Linked to original sources

Chromatographic determination of the association constant between 8-methoxypsoralen and modified beta-cyclodextrin: protective effect of hydroxypropyl-beta-cyclodextrin on 8-methoxypsoralen toxicity in human keratinocytes.

The retention of 8-methoxypsoralen (8-MOP) on an immobilised hydroxypropyl-beta-cyclodextrin (HP-beta-CD) column was analysed in HPLC by the determination of its Langmuir distribution isotherm. A such method was used to confirm the potential drug complexing role of this cyclodextrin. The 8-MOP/HP-beta-CD association constant (K) was equal to 29.5 and 18.7 M-1, respectively, at a temperature equal to 5 and 25 degrees C, respectively. These association constant values were used to determine the cytotoxicity profile of human keratinocyte cell line (HaCaT) in relation to the complex concentration. It was showed through these data that HP-beta-CD had a cytoprotective since a reverse effect of HP-beta-CD on 8-MOP cytotoxicity was observed.

Cell Line↗

[Merkel cell carcinoma: descriptive study of 24 cases (1993-2001)].

INTRODUCTION: Merkel cell carcinoma (MCC) is a rare skin tumor with a highly malignant nature whose appropriate treatment is still debated. Wide surgery is the treatment of choice, but the question concerning protocols for adjuvant radiotherapy or chemotherapy remains open. PATIENTS AND METHODS: A retrospective analysis of 24 cases of MCC collected over a period of 9 years was performed, focusing on clinical and histologic features, and response to treatment. RESULTS: There were 17 women and 7 men with a mean age of 74.3 years. The median follow up was 34 months. The annual incidence per 100,000 habitants was 0.378. The head and neck localization was predominant (54%). Fifteen (68%) of patients presented with local disease (stage I), and 32% of patients presented with regional node (stage II) or distant metastases (stage III). Patients with stage I had a 5-years overall survival rate of 73,85%. Among them, five patients (33%) developed a local or nodal recurrence, although two patients were initially treated with surgery and local post-operative radiotherapy. Patients with stage II and III demonstrated a 5-year overall survival rate of 51,43%. DISCUSSION: Our series illustrates the clinical characteristics of this tumor of the elderly, which is mainly located on head and neck and associated with a poor prognosis. Treatments are discussed.

Aged↗

[Juvenile myelomonocytic leukaemia, xanthoma, and neurofibromatosis type 1].

The triple association of leukemia, xanthogranulomas, and type 1 neurofibromatosis was first described in 1958. Most leukemias were juvenile myelomonocytic leukemias (JMML), usually called juvenile chronic myelogenous leukemia. We describe a 22-month-old female child with neurofibromatosis 1, xanthomagranulomas, and a JMML. Her mother and her brother also had cutaneous café-au-lait spots. Our patient was treated with mercaptopurine and improved. However, 9 months later she experienced a blastic transformation. The presence of xanthomagranulomas and NF1 in a young child should alert to a possible development of JMML, especially in patients with a family history of NF1.

Antimetabolites, Antineoplastic↗

Detection of the human papillomavirus and analysis of the TP53 polymorphism of exon 4 at codon 72 in penile squamous cell carcinomas.

Human papillomaviruses (HPV) are thought to be involved in penile squamous cell carcinomas (SCC). A common polymorphism at codon 72 of exon 4 encoding either arginine (Arg) or proline (Pro) has been shown to affect HPV-mediated degradation of p53 in vitro, and may represent a risk factor for HPV-induced carcinogenesis. The presence of HPV DNA as well as the TP53 polymorphism at codon 72 of exon 4 were investigated in a series of 45 penile SCC. HPV detection and typing were carried out by polymerase chain reaction (PCR) with generic primers (MY09-MY11 and FAP59-FAP64), and type-specific DNA probes. TP53 polymorphism was further investigated using Denaturing Gradient Gel Electrophoresis (DGGE). HPV DNA was detected in 67% of penile SCC and 32% of benign lesions (BL) (P<0.05). Among the TP53 amplified samples, the rate of Arg homozygosity in penile SCC was 61% compared with 68% in BL (non-significant (NS)). Our results demonstrate a strong association between penile SCC and the presence of HPV DNA. The TP53 Arg/Arg genotype does not appear to represent a risk factor for the development of genital SCC in men, and no correlation was found between the TP53 polymorphism at codon 72 and the presence of HPV DNA.

Adult↗

Spectrum of cross-photosensitization in 18 consecutive patients with contact photoallergy to ketoprofen: associated photoallergies to non-benzophenone-containing molecules.

Contact photoallergy to ketoprofen gels has been widely reported, and cross-sensitivity reactions with other compounds, such as tiaprofenic acid, fenofibrate and benzophenones, are well known. However, positive photopatch tests to other different non-benzophenone-related compounds have recently been observed. We report the results of photopatch testing in patients with contact photoallergy to ketoprofen and discuss the spectrum of cross-sensitization to ketoprofen. 18 consecutive patients with a history of photocontact dermatitis from ketoprofen were investigated. Patch and photopatch tests were performed. As expected, we observed positive photopatch tests to Ketum* gel and ketoprofen 2.5% in petrolatum in all patients (100%). However, it was remarkable to note positive photopatch tests to other unexpected and non-relevant allergens, including fentichlor (67%), tetrachlorosalicylanilide (28%), triclosan (17%), tribromsalan (11%) and bithionol (11%), with no clinical relevance. Interestingly, these agents belong to the family of halogenated salicylanilides and related compounds, which have been forbidden in Europe since the 1970s. Our results raise the question of hyper-photosusceptibility to non-relevant allergens induced by photosensitivity to ketoprofen. The mechanism may involve the high photoreactivity induced by the association of a benzene ring with an oxygen group.

Adult↗

[Non-melanoma skin cancers and human papillomavirus].

Ultraviolet radiation (UV) is considered as a key environmental risk factor of non-melanoma skin cancer (NMSC), but other factors such as immunological status, genetic predisposition and infection by human papillomavirus (HPV) may also be involved. Although there is overwhelming epidemiological and molecular evidence that indicates a direct role for specific mucosal HPV-types in anogenital cancers, in particular cervical cancer, the pathogenic role of HPV in the development of NMSC remains speculative. The association between HPV and NMSC was first identified in patients with epidermodysplasia verruciformis (EV) and later in recipients of organ transplants. All these patients develop NMSC at sun-exposed sites. Cutaneous and mucosal HPV-DNA have been detected in about 60 to 90 p. 100 of NMSC, but also in benign epithelial lesions, and even in normal skin. However and although at a lower rate (about 40 p. 100), HPV-DNA have also been detected in normal skin, in particular in hair follicles, and in premalignant lesions and in NMSC from non-EV and immunocompetent subjects. Furthermore, no particular HPV type predominates and the viral load in NMSC seems lower than in benign epithelial lesions. Although all these findings argue against a direct involvement of HPV in NMSC, they may suggest a "hit and run" mechanism which no longer requires the viral agent but the activity of HPV oncoproteins. High risk mucosal HPV-types encode two major oncoproteins, E6 and E7, which inactivate two suppressor proteins, p53 and pRb respectively, and are sufficient for host-cell immortalization. A polymorphism resulting in either a proline or an arginine at codon 72 may also be a relevant risk factor for mucosal HPV-types-associated NMSC. By contrast, E6 of skin HPV-types fails to interact with p53, but prevents infected cells from UV-induced apoptosis leading thus to the propagation of deleterious UV-induced mutations. Immunosuppressive activities of HPV E6 and E7 proteins permit persistent HPV infection and the impairment of immunologic removal of UV-damaged cells. These results support a role for HPV infection in skin carcinogenesis as a co-factor in association with UV and immunosuppression.

Apoptosis↗

[Photocontact dermatitis due to ketoprofen and photosensitization to tetrachlorosalicylanide and to Fenticlor(R)].

BACKGROUND: Photoallergy to ketoprofen and cross reactivity of ketoprofen with diphenylketones are well known; here are some cases of photoreaction to ketoprofen and unusual substances. PATIENTS AND METHODS: Eleven photoallergic to ketoprofen patients were photo patch tested with Ketum(R), ketoprofen, oxybenzone, tiaprofenic acid, fenofibrate, and also chlorphenesin, sunscreen series, and photobiologists series (without lichen mix and benzocaine). We performed tests at day 0, we irradiated them with UVA at day 2, and control series remained closed. We performed readings at day 3 and 4 according to ICDRG's recommendations. RESULTS: Nine tested patients had positive reactions to the irradiated tests with no expected allergens: fenticlor (9 cases), halogenated salicylanilides (4 cases), dibenzoylmethane (3 cases) and cinnamate (1 case). DISCUSSION: The mechanism of these unusual photosensitizations is discussed. These cases show that it is important to test sunscreen series and photobiologists series in patients photoallergic to ketoprofen.

Adult↗

[Cutaneous complications following liver transplantation: epidemiologic and clinical study in 86 patients].

INTRODUCTION: Organ transplanted patients exhibit cutaneous lesions caused by immunosuppressive treatment and/or immunosuppression itself. Several selected studies concerning kidney transplants have been reported, but few concerning liver transplants. We report a retrospective study of skin diseases after liver transplantation. PATIENTS AND METHOD: This study was carried out on liver transplanted patients at the University hospital in Besançon since 1986. Eighty six patients were examined between January 1997 and May 1998. Standardized data obtained at the clinical examination and from past history were compiled concerning cutaneous side effects of immunosuppressive treatments as well as infectious and tumoral skin lesions. RESULTS: Cutaneous side effects related to immunosuppressive treatments: 46.5p. 100 of patients exhibited hypertrichosis, 18.5p. 100 gingival hyperplasia, 8.2p. 100 acne, 23.2p. 100 skin atrophy, 13.9p. 100 senile purpura and 17.4p. 100 sebaceous hyperplasia. Infectious diseases were 2 erysipelas, 2 folliculitis, 29 p. 100 of common fungal infections, 13.9p. 100 of mucocutaneous herpes simplex infections, 3p. 100 of zoster, 38.3p. 100 of cutaneous warts (24.4p. 100 of common warts and 7p. 100 of condylomata). Tumoral skin lesions were 17.4p. 100 of actinic keratoses, 13.9p. 100 of skin cancer (7 squamous and 11 basal cell carcinoma). A correlation was shown between time past graft and the occurrence of skin cancer, between actinic keratoses and skin cancer and between common warts and squamous cell carcinoma. DISCUSSION: We have demonstrated that drug induced skin disorders, infections and tumoral skin diseases were similar and as frequent in liver as in kidney transplanted patients. However, a lower frequency of warts was observed in liver transplanted patients as well as a higher frequency of basal cell carcinoma, compared with squamous cell carcinoma. This ratio is reversed in kidney grafted patients. These results suggest that immunosuppression is lower in liver transplanted patients with possible age involvement.

Adult↗

Intravenous injection of apoptotic leukocytes enhances bone marrow engraftment across major histocompatibility barriers.

Cross-tolerization of T lymphocytes after apoptotic cell uptake by dendritic cells may be involved in self-tolerance maintenance. Furthermore, immunosuppressive properties are attributed to apoptotic cells. This study evaluated the consequences of apoptotic leukocyte administration in a restrictive engraftment model of murine bone marrow (BM) transplantation. Sublethally irradiated recipients received a limited number of allogeneic BM, with or without irradiated apoptotic leukocytes of different origins. No graft-versus-host disease was observed. Whereas only a low proportion of mice receiving BM cells alone engrafted, addition of apoptotic irradiated leukocytes, independently of the origin (donor, recipient, third-party mice, as well as xenogeneic peripheral blood mononuclear cells), significantly enhanced engraftment. Similar results were obtained after infusion of leukocytes rendered apoptotic by UVB irradiation or by anti-Fas monoclonal antibody stimulation, thus confirming the role of apoptotic cells in engraftment facilitation. Overall, these results suggest that apoptotic leukocytes can nonspecifically facilitate allogeneic BM engraftment. Such a simple approach could be of interest in BM transplantation settings involving an important HLA donor/recipient disparity, a T-cell-depleted graft, or reduced conditioning regimen intensity.

Animals↗

[Melanoma: role of ultraviolet radiation: from physiology to pathology].

EPIDEMIOLOGIC DATA: The frequency of malignant melanoma, by far the most fatal skin cancer, has increased by a factor of approximately 15 in the past 60 years. The factors underlying this rapid increase are incompletely understood, although ultraviolet radiations are likely strongly implicated. Epidemiologic studies demonstrate the role of altered patterns of sun exposure, and overexposition to UVA radiation, as confirmed by experimental data on animal models. BIOLOGICAL ASPECTS: Melanin produced by melanocytes has a photoprotective function in the skin, whereas UVB-induced DNA damage enhance the repair capacity of these cells. However, this photoprotective effect is not induced by intense intermittent sun exposure. In addition, melanocytes demonstrate resistance to UVB-induced apoptosis and are thus at high risk for incorporating UV-induced mutations. MOLECULAR ASPECTS: Different mutations in susceptibility genes (CDKN2A, INK4), or in genes implicated in control of cell cycle or maintenance of cell integrity (DNA repair) are involved in initiation and promotion steps of melanocarcinogenesis. Moreover, tumor progression is stimulated by UVB through the activation of different target genes that are implicated in control of melanoma environment (immune surveillance, angiogenesis, growth factors...).

Adolescent↗

Genital squamous cell carcinoma in men treated by photochemotherapy. A cancer registry-based study from 1978 to 1998.

BACKGROUND: One single report from the U.S. 16-centre-trial indicated that psoralen and ultraviolet A radiation (PUVA) therapy may induce an increased risk of genital tumours in men, and protection of the genital area is, therefore, recommended. OBJECTIVES: To evaluate the relevance of this risk in routine clinical practice. METHODS: Two groups of patients were included in a 1978-98 retrospective study. Case records of men with genital squamous cell carcinoma (SCC) identified from the Cancer Registry of the Doubs area of France were examined for a history of PUVA therapy, topical tar treatment, psoriasis, human papillomavirus infection or genital dermatitis. In addition, all the dermatologists of the Doubs area (in public and private practice) using PUVA therapy were asked to provide information on the number of patients having received PUVA therapy and whether the genital area was exposed during treatment. RESULTS: Between 1978 and 1998, among the 48 men who had developed a genital SCC in the Doubs area, only one had a history of intensive PUVA therapy. About 150,000 treatments with PUVA therapy had been performed by 15 dermatologists in the Doubs area for 5400 patients since 1978. No case of genital SCC had been reported, despite the fact that the genital area had not been protected during UVA exposure. CONCLUSIONS: Although retrospective, our study demonstrates that the occurrence of genital SCC in men treated with PUVA therapy is a very rare event in common dermatological practice.

Adult↗

Delays in diagnosis and melanoma prognosis (II): the role of doctors.

A prospective survey was conducted to assess physician responsibility in melanoma prognosis. Consecutive patients with primary melanoma were interviewed and examined using a standardized questionnaire. Main outcome measures were medical components of the delay before tumor resection and tumor thickness. Of 590 melanomas, 29.1% were coincidentally detected by physicians and their tumor depth was lower than in melanomas detected by patients (p < 0.001). Physician sensitivity for melanoma diagnosis was evaluated at 86%. Median time intervals to propose resection and to perform removal of melanoma were short: 0 (mean 103) and 7 (mean 68) days, respectively. Melanomas were managed in an inappropriate way in 14.2% of cases. Location on acral areas and absence of pigmentation were associated with longer medical delays and more frequent inappropriate medical attitudes. Melanomas located on hardly visible areas were less frequently detected by physicians than those on visible areas. Medical delays were shorter, doctor's attitude was more frequently appropriate, and melanoma thickness was lower (p < 0.001) when the patient visited a dermatologist (54.7%) than when he or she visited a general practitioner (33.4%). Our study shows that doctor responsibility accounts for only a small part of the total delay before melanoma removal. However, systematic total examination and better training of doctors, especially about unusual forms of melanoma, could still improve melanoma detection.

Attitude of Health Personnel↗

Delays in diagnosis and melanoma prognosis (I): the role of patients.

A prospective survey was conducted to assess the role of patients in the melanoma prognosis. Consecutive patients with primary melanoma were interviewed and examined using a comprehensive questionnaire including a psychological instrument. Main outcome measures were the delay before medical intervention and the tumor thickness. Of 590 melanomas, 70.8% were detected by patients and this proportion was higher in females. Relatives were involved in the detection of half of the cases. Median delays before the patient realized he had a suspicious lesion, before this lesion was seen by a doctor, and before the melanoma was removed were 4 months, 2 months, and 1 week, respectively. Delays up to several years were observed in some cases. The rate of self-detection tended to be lower, the delays before seeking medical advice to be longer, and the tumor thickness to be higher in old people, in males, in lower-educated individuals, in those living out of towns, and in people with a low awareness about melanocytic tumors than in other cases. Conversely, individuals with a high number of atypical nevi, those who were aware to be at risk, and those who regularly visited a dermatologist tended to detect their melanoma more rapidly. No specific psychological traits were associated with a late reaction, although negligence and anxiety tended to prolong the delays. Knowledge about melanoma was poor in many patients, especially in males, and wrong beliefs were widespread. This study provides the targets of future education programs.

Adolescent↗

Extensive vitiligo after ganciclovir treatment of GvHD in a patient who had received donor T cells expressing herpes simplex virus thymidine kinase.

The use of donor T cells expressing a suicide gene for destruction of graft-versus-host effector cells provides a tool for alloreactivity modulation. We describe a case of extensive vitiligo that developed after ganciclovir treatment of cutaneous chronic graft-versus-host disease in a patient who had received donor T lymphocytes expressing herpes simplex virus thymidine kinase at the time of transplantation.

Adult↗

A prognostic study of clinical dimensions in adolescent-onset psychoses.

Adolescent-onset psychoses often raise diagnostic difficulties because of the mixture of schizophrenic and affective features. This study examined prospectively which clinical dimensions contribute to difficulty in initial diagnosis and which clinical features have predictive value for outcomes of schizophrenia or affective disorders, and for eventual psychosocial functioning. Thirty-six adolescents consecutively admitted for a psychotic episode were followed up for 1 to 4 years. Symptoms were assessed at admission, at discharge, and once a year. DSM-III-R (APA 1989) diagnoses were assessed at admission and once a year. Comparisons were performed across initial and followup diagnostic groups. Positive symptoms did not differentiate the initial clinical pictures, while negative symptoms, manic symptoms, and disorganization differentiated the manic and depressive episodes in the acute phase. When initial positive symptoms (mainly delusions) were severe, they predicted a final diagnosis in the schizophrenia spectrum. Poor outcome was associated with more anhedonia-associality and lower functioning scores at admission. Results suggest (1) a higher vulnerability to positive symptoms in adolescents who will further develop schizophrenia and (2) the low specificity of affective symptoms at this age.

Acute Disease↗

Skin manifestations associated with toxocariasis: a case-control study.

BACKGROUND: Human toxocariasis is one of the most common zoonotic helminthiases. The recent development of sensitive and specific diagnostic laboratory tests has led to identify a large spectrum of diseases, including cutaneous diseases, induced by Toxocara infection. OBJECTIVE: The purpose of our study was to assess the risk of having a positive Toxocara ELISA test in patients with different cutaneous symptoms. METHODS: The diagnosis of toxocariasis was based on an ELISA test which was performed in 653 patients suffering from different skin conditions during a prospective case-control study. RESULTS: The excess of risk (adjusted odds ratio) of having a positive result in the Toxocara ELISA was statistically significant for 134 patients with urticaria (whatever the clinical presentation) and for 22 patients with prurigo compared to a control group (249 patients). No statistical excess of risk was observed for patients with atopic dermatitis, pruritus or non-atopic eczema. CONCLUSION: The authors conclude that patients suffering from urticaria or prurigo should be tested for Toxocara infection. Whether these patients should be treated with anthelminthic drugs remains to be determined in further studies.

Adolescent↗

[Melanoma in organ transplant patients].

OBJECTIVE: The incidence of cutaneous melanoma has rapidly increased in the white population over the last decades. It has been estimated that the incidence doubles world-wide every 10 years. Different risk factors have been identified, including immunosuppression. The aim of our study-was to determine the relative risk of developing melanoma in the organ transplant population and the clinical and histological features of their melanomas. PATIENTS AND METHODS: This retrospective study was conducted with the collaboration of 9 University Hospital Centers: Besançon, Brest, Caen, Dijon, Lille, Lyon, Nantes, Paris (Pitié-Salpétrière) and Rennes. A questionnaire was sent to the different departments of dermatology of these hospitals to obtain information on patients who had presented a melanoma after a transplantation between 1971 and 1997. During this period, there were 12,477 organ transplant recipients in the transplantation units of these 9 hospitals. Average follow-up for these patients was about 5 years and the average duration of immunosuppressive therapy was about 4.5 years. RESULTS: Among 12,477 organ transplant recipients, we found 17 cases of melanoma but no data could be obtain on one case: 14 occurred in renal transplant recipients and 3 in cardiac transplant recipients. Clinical and histological data were only available in 16 patients. The average time between transplantation and diagnosis of melanoma was 63 months, but it was 5 times shorter for 2 patients who had a past history of melanoma before transplantation. Two patients had a mucosal melanoma; for the cutaneous melanomas, 2 appeared on Dubreuilh melanosis, 2 were in situ melanomas, 7 were superficial spreading melanomas and 3 were nodular melanomas. The histological review of 11 cutaneous melanomas revealed a precursor nevus in 6 cases and a weak or no stroma reaction in 7/7 cases. Complete excision of the melanoma was performed in all patients except one with anorectal melanoma. Four patients died of visceral metastasis within a mean 15 months. The other 12 patients are still alive with a mean 3 year course since tumor treatment. We tried to determine the relative risk of developing melanoma in the renal transplant population (14 cases). The number of expected cases of melanoma was 5.54, giving a relative risk of 2.5. DISCUSSION: Only 4 studies have shown an increase in the incidence of melanoma in the renal transplant population: approximately 2 to 5-fold. In our study, the 2.5-fold increase in melanoma was estimated with an average 5 year follow-up and an average 5 year immunosuppressive therapy. This is probably an underestimation of risk because we were unable to make an exhaustive collection of cases of melanomas even though transplant recipients undergo more physical examinations than a reference population. The mean latency period from transplantation to melanoma diagnosis was 63 months, as in other studies. Histological examination showed that a precursor nevus is frequent with weak host cellular response to the tumor. The prognosis of these melanomas remains difficult to predict, but in our study, it would not appear to be as poor as expected. Discontinuation of immunosuppressive therapy would not appear to be necessary except in the presence of metastasis. Finally, our study demonstrates the importance of good patient follow-up, even after graft rejection due to the persistent risk of melanoma.

Adult↗