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Biomedical subjects

R Laurent

Publications and source records attributed to R Laurent.

At least 19 recordsLinked to original sources

Dermatofibrosarcoma protuberans: a population-based cancer registry descriptive study of 66 consecutive cases diagnosed between 1982 and 2002.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a rare malignant tumour of the skin, with an estimated incidence of 0.8 to five cases per 1 million people per year. OBJECTIVE: To study epidemiological, immunohistochemical and clinical features, delay in diagnosis, type of treatment and outcome of DFSP from 1982 to 2002. METHODS: Using data from the population-based cancer registry, 66 patients with pathologically proved DFSP were included (fibrosarcomatous DFSP were excluded). Each patient lived in one of the four departments of Franche-Comté (overall population of 1 million people) at the time of diagnosis. The main data sources came from public and private pathology laboratories and medical records. The rules of the International Agency for Research on Cancer were applied. RESULTS: The estimated incidence of DFSP in Franche-Comté was about three new cases per 1 million people per year. Male patients were affected 1.2 times as often as female patients were. The trunk (45%) followed by the proximal extremities (38%) were the most frequent locations. DFSP occurred mainly in young adults between 20 and 39 years of age. Mean age at diagnosis was 43 years, and the mean delay in diagnosis was 10.08 years. Our 66 patients initially underwent a radical local excision. Among them, 27% experienced one or more local recurrences during 9.6 years of follow-up. There was one regional lymph node recurrence without visceral metastases. These recurrences were significantly related to the initial peripheral resection margins. We observed a local recurrence rate of 47% for margins less than 3 cm, vs. only 7% for margins ranging from 3 to 5 cm [P=0.004; OR=0.229 (95%, CI=0.103-0.510)]. The mean time to a first local recurrence was 2.65 years. Nevertheless, there was no death due to the DFSP course at the end of the follow-up, and the final outcome was favourable. CONCLUSION: Our study emphasizes the importance of wide local excision with margins of at least 3 cm in order to prevent local recurrence. However, the recent development of inhibitors of signal transduction by the PDGFB pathway should soon modify the surgical strategy, which is often too mutilating.

Adolescent↗

[Cutaneous drug-reactions to nevirapine: study of risk factors in 101 HIV-infected patients].

BACKGROUND: Several studies have shown a high prevalence of rash induced by nevirapine. However, there is little knowledge about the risk factors associated with nevirapine-induced rash. The aim of this study was to identify risk factors associated with the occurrence of rash during the treatment with nevirapine of HIV-infected patients. METHODS: A retrospective study was conducted in the dermatology department of Besançon university teaching hospital between November 1998 and September 2001. The study included all HIV-infected patients receiving HAART regimens that included nevirapine. The following data were collected: age, sex, CDC classification of HIV, CD4 and CD8 lymphocyte counts, plasma HIV RNA load, hepatitis B, C and cytomegalovirus serostatus, history of drug allergy, concomitant medication (other antiretroviral drugs, corticosteroids, antihistamines). Univariate analysis was performed using a Chi2 test or Fischer's test and Student's t test. Fischer's test and the Cox proportional hazards model were used in the multivariate analysis. RESULTS: During the study period, 101 HIV-infected patients (74 men and 27 women; mean age: 41.6 +/- 10.3 years) were treated with HAART regimens including nevirapine. Fourteen developed cutaneous drug-reactions attributable to nevirapine (13.86%). We observed 13 cases of maculopapular exanthema and 1 case of DRESS. In the univariate analysis, female gender (p=0.002), plasma HIV RNA load > 10,000 copies/ml (p=0.05), heterosexual transmission (p=0.002) and abacavir treatment (p=0.05) constituted risk factors associated with rash. In the multivariate analysis, only female gender (p<0.0001) and plasma HIV RNA load > 10,000 copies/ml (p=0.0007) were associated with rash. DISCUSSION: The results of this study confirm the high frequency of toxidermy associated with nevirapine therapy. The risk factors associated with occurrence of rash due to nevirapine therapy were female gender and plasma RNA > 10,000 copies/ml. Several studies showed absence of any protective effect of antihistamines and corticosteroids in preventing the cutaneous adverse reactions associated with nevirapine. The identification of risk factors closely associated with nevirapine-induced rash could help physicians determine new strategies for safer use of nevirapine in the HAART regimen.

Adult↗

Evaluation of a novel 308-nm monochromatic excimer light delivery system in dermatology: a pilot study in different chronic localized dermatoses.

BACKGROUND: Recently, units have been developed that are capable of delivering large fluences of narrowband ultraviolet (UV) B selectively to cutaneous lesions within a reasonable time. OBJECTIVES: To analyse the efficacy of a novel nonlaser 308-nm monochromatic excimer light (MEL) delivery system in various dermatoses usually treated by narrowband UVB phototherapy. METHODS: Fifty-four patients with chronic and resistant localized dermatoses were enrolled in a prospective study: 17 with palmoplantar pustular psoriasis, seven with plaque-type psoriasis, four with nail psoriasis, eight with chronic atopic dermatitis of the hands, 10 with chronic nonatopic dermatitis of the hands and eight with alopecia areata. The 308-nm xenon chloride MEL delivery system (Excilite; DEKA, Florence, Italy) was used to produce an average incident dose rate of 50 mW cm(-2) at a tube-to-skin distance of 15 cm and with a maximum irradiating area of 512 cm2. The initial dose was based on multiples of a predetermined minimal erythema dose (MED), and subsequent doses were based on the response to treatment. Treatments were scheduled weekly for a maximum of 10 weeks. Clinical responses were evaluated using photographic documentation and (except for alopecia areata) clinical score. RESULTS: The MED ranged from 250 to 350 mJ cm(-2) (mean +/- SD 318.2 +/- 28.4). MEL at 308 nm was the most effective for palmoplantar pustular psoriasis with a mean improvement of 79% after a mean of 5.3 treatments and a mean dose of 11.8 MED per treatment. Plaque-type psoriasis was significantly less sensitive to treatment and nail psoriasis demonstrated no benefit from treatment. Chronic palmar atopic dermatitis was cleared in two patients and the mean improvement was 54% as compared with 46% in patients with chronic nonatopic dermatitis of the hands. Four complete regrowths among the eight patients with alopecia were observed after a mean of 5.1 treatments. The percentages of improvement had significantly decreased at the 6-month visit, and only four patients (24%) with palmoplantar pustular psoriasis still demonstrated a significant improvement. Common side-effects included intense erythema and, more rarely, blisters, but these were well tolerated. CONCLUSIONS: Our preliminary results confirm the efficacy of this novel 308-nm MEL delivery system, which appears to be effective and safe for palmoplantar pustular psoriasis. To a lesser extent, plaque-type psoriasis, chronic atopic and nonatopic dermatitis of the hands and alopecia may also benefit from this treatment.

Adult↗

Circulating vascular endothelial growth factor in cutaneous malignant melanoma.

BACKGROUND: Angiogenesis has been reported as a parameter of potential prognostic value in solid tumours, as it may facilitate tumour growth and metastasis. One of the most important growth factors involved in angiogenesis is vascular endothelial growth factor (VEGF). OBJECTIVES: To determine the predictive value of circulating VEGF levels in a cohort of patients with melanoma. METHODS: In a prospective cohort study, 324 patients with cutaneous melanoma at different clinical stages were investigated over 2 years (2002-04). VEGF was measured in plasma using enzyme-linked immunosorbent assay. Two hundred and eight patients were able to be followed up for progression of their disease and for blood sample collection (mean +/- SD follow-up 13.4 +/- 0.8 months). Data were compared with the extent of the disease and the clinical course. RESULTS: A significant increase in plasma VEGF levels was found in patients with melanoma compared with healthy controls, with statistically significant differences between patients in stages I, II and III vs. those in stage IV, but not between patients in stages I, II and III. When considering the 237 patients in stages I and II, no statistical correlation was found between plasma VEGF levels and tumour thickness. Baseline plasma VEGF levels were not significantly higher in patients who relapsed compared with nonprogressing patients. Among the 35 patients (two stage I, eight stage II and 25 stage III) who experienced a progression during follow-up, an increase in plasma VEGF level to > 100 pg mL(-1) was found in 20 (sensitivity 57.1%), while 38 of the 173 remaining nonprogressing patients demonstrated an increase in VEGF level, indicating a specificity of 78%. In addition, an increase in plasma VEGF level was found in 58 patients during follow-up, of whom 20 showed evidence of progression, indicating a positive predictive value of 34.5%. However, among the 150 remaining patients who did not demonstrate any increase in plasma VEGF level during follow-up, only 15 experienced a progression, indicating a negative predictive value of 90%. CONCLUSIONS: Our data confirm that blood VEGF levels are significantly increased in patients with melanoma and, more interestingly, that the absence of plasma VEGF level increase during follow-up appears to be associated with remission.

Disease Progression↗

[Effects of imiquimod on latent human papillomavirus anal infection in HIV-infected patients].

INTRODUCTION: High risk human papillomaviruses (HPV) have emerged as risk factors for anal carcinoma particularly in HIV-infected patients who demonstrate a high rate of anal HPV infection. Considering the relationship between the presence of anal infection and the development of neoplastic lesions, we wished to assess the capacity of imiquimod to eradicate latent HPV infection in HIV-infected patients. PATIENTS AND METHODS: We conducted a prospective, randomized, double-blind and vehicle controlled study. Two consecutive anal swabs were taken at 2 month intervals and only patients with two consecutive tests positive for the detection of HPV-DNA (Hybrid Capture II) were included. Patients with persistent latent HPV infection were divided into 2 groups who applied imiquimod versus vehicle during 6 weeks. HPV-DNA presence was then investigated 2 and 4 months following the onset of treatment. RESULTS: Among the 80 HIV-infected patients, 26 (32.5 p. 100) had 2 positive consecutive assays, and 19 patients were included in the study. After randomization, 9 patients received imiquimod and 10 vehicle. There was no significant difference between treatment groups according to the following criteria: gender, route of HIV transmission, CDC stage, prior medical history of sexually transmitted diseases or anogenital warts. 33.3 p. 100 (3/9) of patients treated with imiquimod were negative at M2, whereas 100 p. 100 (10/10) vehicle treated-patients remained positive (p=0.08). Similar results were observed at the M4 visit. DISCUSSION: Our study confirmed the increased prevalence of latent HPV-DNA infection in HIV-infected patients. In spite of the low number of treated patients, we did not observe a statistically significant decrease in HPV-DNA in anal swabs from imiquimod-treated patients as compared to placebo-treated patients.

Adjuvants, Immunologic↗

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↗

[Multiple familial cutaneous leiomyoma].

INTRODUCTION: Cutaneous leiomyoma is a benign tumor, the discovery of which may suggest a hereditary form. We report a family in which 5 generations developed cutaneous and uterine leiomyomas. The originality of this report lies in the large number of generations developing the disease and the association with chronic myeloid leukemia. OBSERVATIONS: We have studied 16 members of a family with cutaneous and uterine leiomyomas spanning five generations. Eight members of the family (6 women and 2 men) presented with cutaneous leiomyomas. All 6 women also had uterine myomas with complications (menometrorrhagia, miscarriage, premature delivery and hysterectomy). Pathological association was also confirmed: polycythemia (1 case), papillary renal carcinoma (1 case) and chronic myeloid leukemia (1 case). DISCUSSION: Piloleiomyoma can develop sporadically or can be transmitted genetically. To our knowledge, we report the fifth case of a family of more than 2 generations presenting with piloleiomyoma. By studying the family tree, we were able to confirm the dominant autosomal nature of the mode of transmission found by other authors. The association of piloleiomyoma and uterine myoma is classified as Reed's syndrome. In such cases, the uterine myoma requires particularly careful monitoring since it is associated with significant risk of gynecological complications (menometrorrhagia, miscarriage, premature delivery and postpartum hemorrhage). Moreover, in our observations we describe diseases associated with piloleiomyoma: polycythemia (1 case), papillary renal carcinoma (1 case), but also the association of piloleiomyoma with chronic myeloid leukemia (1 case). A previous report described the same genetic deletion in uterine myoma as in chronic myeloid leukemia, which gives further weight to this association.

Adult↗

[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↗

[Rosacea].

Explore the source record for details and available documents.

Humans↗

[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↗

Longitudinal study of anti-Candida albicans mucosal immunity against aspartic proteinases in HIV-infected patients.

Oropharyngeal candidiasis (OPC), mainly caused by Candida albicans, is commonly observed in HIV-infected patients. Secreted aspartic proteinases (Saps) are virulent agents involved in adherence to the mucosal surface and in tissue invasion. The immune secretory response to these agents was investigated in 15 HIV-infected patients, during oral yeast colonization and episodes of oropharyngeal candidiasis (OPC), in a 1-year longitudinal study. We developed an avidin-biotin-amplified immunofluorometric assay for the detection of specific immunoglobulins G, A, and M against somatic, Sap2 and Sap6 antigens. We report increases in anti-somatic, anti-Sap2, and anti-Sap6 salivary antibodies in patients with OPC. Over the 1-year period, not only OPC episodes but also variations in yeast colonization levels were correlated with variations in salivary anti-Sap6 antibody levels. Our results show the ability of HIV-infected patients to produce high levels of salivary antibodies; however, these antibodies were not efficient in limiting candidal infection, probably because of cellular cooperation deficiency and the enhanced virulence of the infecting strain.

AIDS-Related Opportunistic Infections↗

Role of the observed long case in postgraduate medical training.

BACKGROUND: The teaching of long case examination technique emphasizes case presentation, problem identification and discussion of management. It assumes that history taking and ability to perform a complete physical examination in a limited time are adequate. These can only be assessed by directly observing the long case examination. AIMS: To explore the usefulness of observing long case performance. METHODS: We used a structured assessment form to observe and evaluate the overall long case performance of 19 doctors in our physicians' training programme. Nine, group A, had received 6 months training, whereas the 10 in group B had only just commenced clinical examination training. RESULTS: Ten (53%) passed their long case, seven from group A and three from group B. Thirteen (68%) passed the history and examination section. Three failed the history component and five failed the examination component. The groups had similar scores for observed history taking. Common problems included poor time management, excessive time required to take the history and lack of organization of questions. Physical examination was usually poorly organized, requiring the use of short cuts, particularly in the respiratory, musculoskeletal and neurological systems. Group A were better at presentation and discussion, with eight (89%) passing compared with four (40%) passing in group B. CONCLUSION: These results reflect the emphasis in our training programme on long case discussion and management, rather than examination technique. The observed case allowed for detection of defects in history-taking skills and time management. Therefore, it is valuable in preparing candidates for their Fellowship examinations.

Australia↗

Increased serum and salivary immunoglobulins against Candida albicans in HIV-infected patients with oral candidiasis.

The aim of this study was to explore anti-Candida albicans systemic and mucosal humoral responses against Candida virulence antigens such as somatic antigen and secreted aspartic proteases (Saps) in HIV-infected patients with oral candidiasis. Twenty-eight subjects were included in the study: 11 HIV-positive patients without oral candidiasis (group A), 6 HIV-positive patients with oral candidiasis (group B) and 11 HIV-negative healthy controls (group C). Total IgA, IgG and IgM concentrations and antibodies to C. albicans (somatic antigen, Sap1, Sap6) were measured in serum and saliva. We developed a time-resolved immunofluorometric assay with biotin and europium-labeled streptavidin for this purpose. Salivary total IgA, IgG and IgM concentrations were higher in group B. IgA, IgG and IgM anti-C. albicans antibodies (against somatic antigen, Sap1, Sap6) were higher in saliva and serum from patients from group B compared with patients from group A and controls. Our results suggest that, in oral candidiasis, HIV-infected patients have a high mucosal response, specifically directed against C. albicans virulence antigens, such as somatic antigen, Sap1 and Sap6.

AIDS-Related Opportunistic Infections↗