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Biomedical subjects

F Aubin

Publications and source records attributed to F Aubin.

At least 19 recordsLinked to original sources
PubMed2001

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↗
PubMed2001

[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↗
PubMed2001

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

[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↗
PubMed2000

The detection of tyrosinase mRNA in the peripheral blood of stage I melanoma patients is not of clinical relevance in predicting metastasis risk and survival.

The presence of tyrosinase mRNA in the peripheral blood cells of melanoma patients has been recently studied as a possible marker of haematogenous dissemination. However, considerable variations in the rates of detection have been noted. We determined the presence of tyrosinase mRNA-positive circulating cells using reverse transcriptase-polymerase chain reaction (RT-PCR) in 35 patients with stage I melanoma, two patients with stage II melanoma and two patients with stage III melanoma. Among the patients with stage 1, 13 were tested before and after surgery (< 1 h). Twenty healthy subjects served as negative controls. Out of the melanoma patients, the tyrosinase gene was expressed in three of the 52 samples tested. Tyrosinase mRNA was present in the circulating cells of only one patient with stage I melanoma after intra-congenital naevi resection. However, two other stage I patients developed rapidly lethal metastasis within the following 6 months, despite the lack of detectable tyrosinase mRNA. None of stage II patients were positive for the tyrosinase transcripts, while both patients with stage III melanoma showed enzyme expression. Our results confirm those of previous studies, showing that a small proportion of stage I melanoma patients have tyrosinase-positive circulating cells. Moreover, the lack of tyrosinase mRNA detection in the blood does not necessarily exclude metastatic progression. Therefore, this study indicates that the detection of tyrosinase mRNA-positive circulating cells by RT-PCR is not a predictive biomarker of a metastasis risk in patients with stage I melanoma.

Biomarkers, Tumor↗
PubMed2000

[Subcutaneous fat necrosis of the newborn with hypercalcemia].

INTRODUCTION: Hypercalcemia associated with subcutaneous fat necrosis of the newborn is a well known but rare event. CASE REPORT: A newborn with a history of cesarean section, fetomaternal infection, neurological and respiratory distress was admitted with anorexia, adynamia, vomiting, polyuria and polydipsia at the age of 37 days. Physical examination showed red and violaceous infiltrated skin lesions. Skin biopsy revealed focal areas of fat necrosis with crystal-like structures. Calcium and 1,25 (OH(2) ) vitamin D serum levels were increased. Diagnostic of subcutaneous fat necrosis of the newborn with symptomatic hypercalcemia was made. Evolution was favorable after treatment including furosemide, prednisone and a diet low in calcium and vitamin D. DISCUSSION: Hypercalcemia must be detected in infants with subcutaneous fat necrosis. This major complication may have fatal outcome. Treatment of hypercalcemia includes dietary changes associated with classic treatment of hypercalcemia. Routine evaluation of serum calcium level is essential.

Fat Necrosis↗
PubMed1999

Melanoma and tumor thickness: challenges of early diagnosis.

OBJECTIVE: To test the basic assumption of campaigns for early diagnosis of melanoma, ie, prognosis is correlated with the delay in the diagnosis. DESIGN: Prospective study of the correlation between delays to diagnosis, assessed using a questionnaire, and the Breslow thickness as a prognosis marker. SETTING: Dermatology departments in France. PATIENTS: Five hundred ninety consecutive patients, referred within 12 weeks after resection of cutaneous melanoma. MAIN OUTCOME MEASURES: Assessment of 5 successive time intervals from the first time the patients realized that they had a lesion until the resection of the melanoma, and results of the correlation between each time interval and tumor thickness (Breslow). RESULTS: There is a positive but weak correlation between tumor thickness and the delay to identify a lesion as suspicious (r = 0.17; P = .009). However, this delay tends to be short for the thickest tumors. There is a negative correlation between tumor thickness and the delay to seek medical attention (r = -0.20; P<.001). This delay was shorter for nodular melanoma. No correlation is found between melanoma thickness and physicians' delays. CONCLUSIONS: Poor prognosis can be accounted for by aggressive rapidly growing tumors rather than by delays. In well-informed populations, campaigns for early diagnosis of melanoma may thus no longer have a major impact on prognosis, unless they are focused on subgroups less accessible to information and medical care.

Female↗
PubMed1999

Cutaneous reaction to ultraviolet irradiation in human-immunodeficiency-virus-infected patients. A case-control study.

BACKGROUND: HIV-infected patients, like renal transplant recipients, are at increased risk of developing skin cancer in photoexposed areas. Previous studies demonstrated that prolonged ultraviolet (UV)-induced erythema and a decreased and delayed tanning could be correlated with an increased risk of skin cancers. OBJECTIVE: As HIV-infected patients are at an increased risk of developing skin cancers, we aimed to assess the cutaneous response to UV irradiation in these patients. METHODS: Twelve HIV-infected patients and 12 healthy volunteers were included in a prospective case-control study. No patient or volunteer had a history of skin cancer or photodermatosis. The minimal erythemal dose (MED) was determined using a solar simulator UV source, and, then, each subject underwent an exposure of 6 MED. The erythemal and pigmentation responses were studied using a visual scale and a tristimulus colorimeter over a 4-week period. RESULTS: We failed to demonstrate any significant differences between HIV-infected patients and controls for erythema and delayed pigmentation. No difference was found for MED between the two groups although most HIV-infected patients received potentially photosensitive drugs. CONCLUSIONS: Our results suggest that, as a group, the HIV-infected patients without a history of photosensitivity or skin cancer did not demonstrate a greater susceptibility to intense UV irradiation in terms of erythema and pigmentation induced by intense UV exposition.

Adult↗