Comparative transcriptional and phenotypic peripheral blood analysis of kidney recipients under cyclosporin A or sirolimus monotherapy.

Due to its low level of nephrotoxicity and capacity to harness tolerogenic pathways, sirolimus (SRL) has been proposed as an alternative to calcineurin inhibitors in transplantation. The exact mechanisms underlying its unique immunosuppressive profile in humans, however, are still not well understood. In the current study, we aimed to depict the in vivo effects of SRL in comparison with cyclosporin A (CSA) by employing gene expression profiling and multiparameter flow cytometry on blood cells collected from stable kidney recipients under immunosuppressant monotherapy. SRL recipients displayed an increased frequency of CD4 + CD25highFoxp3 + T cells. However, this was accompanied by an increased number of effector memory T cells and by enrichment in NFkB-related pro-inflammatory expression pathways and monocyte and NK cell lineage-specific transcripts. Furthermore, measurement of a transcriptional signature characteristic of operationally tolerant kidney recipients failed to detect differences between SRL and CSA-treated recipients. In conclusion, we show here that the blood transcriptional profile induced by SRL monotherapy in vivo does not resemble that of operationally tolerant recipients and is dominated by innate immune cells and NFkB-related pro-inflammatory events. These data provide novel insights on the complex effects of SLR on the immune system in clinical transplantation.

[Pseudoaneurysm of the hepatic artery: rare complication of chronic pancreatitis]. / Pseudoanevrisme de l'artere hepatique: complication rare au cours de l'histoire naturelle de la pancreatite chronique: à propos de deux cas.

Bleeding from a pseudoaneurysm is a rare complication of chronic pancreatitis. We present two cases of ruptured pseudoaneurysms of the hepatic arteries. The first case involved a pancreatic pseudocyst that ruptured in the duodenum and the second resulted in an intrahepatic hematoma that compressed the bile tract causing secondary hemobilia. Angiographic embolization was the primary treatment in both cases, with surgery for the first patient and later radiological drainage in the second. The hemorrhage was controlled in both cases despite the severe prognosis and high mortality in these cases.

TCR usage in naive and committed alloreactive cells: implications for the understanding of TCR biases in transplantation.

The direct pathway of allorecognition is involved in acute allograft rejection and is characterised by TCR-mediated recognition of the MHC framework; this is thought to occur in a peptide-dependent but not peptide-specific manner. In contrast, the indirect pathway is restricted to the recipient's own MHC molecules and prevails in chronic rejection. In this pathway, the peptide has a major influence on the TCR recognition and selects alloreactive T cells with altered TCR Vbeta usage. However, qualitative analysis of Vbeta usage alone might limit our understanding of alloreactivity. The advantages of a combined quantitative assessment of Vbeta mRNA usage are discussed.

[Clinical efficacy of eculizumab as treatment of gemcitabine-induced thrombotic microangiopathy: A case report]. / Efficacité de l'éculizumab comme traitement de la microangiopathie thrombotique induite par la gemcitabine : à propos d'un cas.

INTRODUCTION: Gemcitabine-induced thrombotic microangiopathy is a rare event whose management is not yet consensual. The use of eculizumab could be of interest. CASE REPORT: A 68-year-old woman was treated by gemcitabine as adjuvant chemotherapy of a pancreatic adenocarcinoma. Two months later, the patient presented with mechanical hemolytic anemia, thrombocytopenia and high blood pressure that led to the diagnosis of thrombotic microangiopathy. Gemcitabine was stopped. Plasma exchange therapy was introduced since hematological and renal parameters had worsened. As clinical efficacy was insufficient, eculizumab was introduced at a dose of 900 mg per week 4 times, then 1200 mg every 2 weeks. Symptoms along with hematological and nephrological analysis were back to physiological standards after 7 intravenous injections. CONCLUSION: Eculizumab seems to be an effective treatment against gemcitabine-induced thrombotic microangiopathy in case of severe hematological and renal injuries associated with a lack of response to plasma exchange therapy.

Performance of porcine corneal opacity and permeability assay to predict eye irritation for water-soluble cosmetic ingredients.

The purpose of this paper is to report on the ability of an in-house porcine corneal opacity and permeability assay (PCOP) to predict eye irritation for cosmetic ingredients. Preliminary studies showed that the PCOP assay could accurately predict eye irritation class for liquid and water soluble materials. To broaden our experience a larger study on 50 cosmetic ingredients of this group was conducted. A prediction model (PM) was obtained based on only one endpoint-permeability measured after 30-min exposure O.D.30. This PM allows to distinguish nonirritating compounds (if O.D.30 < 0.35) from irritating (if O.D.30 > or = 0.35). Forty-nine of the 50 ingredients tested in the PCOP assay were accurately classified. The agreement was high (concordance 98%-kappa = 0.96). For 43 of the test substances an equation PM was obtained to predict the MAS. Despite satisfactory statistical coefficients this algorithm is not recommended due to wide 95% confidence intervals. These results confirm the usefulness of the PCOP for water-soluble cosmetic ingredients to discriminate nonirritants (MAS < or = 15) and irritants (MAS >15). For this type of ingredients the PCOP seems to be better than the BCOP to predict irritation class. Future work will be done to compare the BCOP and PCOP performances and to develop an appropriate protocol for water insoluble compounds.

[Vulvar contact dermatitis due to seminal allergy: 3 cases]. / Vulvite d'hypersensibilité aux protéines séminales: 3 cas.

BACKGROUND: Contact sensitivity deserves to be assessed in acute vulvitis as well as chronic vulvar dermatitis with a specific orientation toward semen allergy whenever the pathology is post-coital. OBSERVATIONS: Three observations of semen allergy are reported. Two women presented with post-coital vulvitis due to delayed hypersensitivity to semen proteins without associated specific IgE. The type 2 allergy was confirmed by positive patch-tests and disappearance of symptoms when using condoms. Another woman presented with oedematous vulvitis associated with asthma and malaise per and post-sexual intercourse. Positive prick-tests with husband's semen and blood tests for specific IgE led to the diagnosis of type 1 hypersensitivity to semen, with disappearance of both vulvar and systemic symptoms with the use of condoms. DISCUSSION: Immediate or delayed type hypersensitivity may be discovered using prick and patch tests respectively. The observation of vulvitis or vulvar discomfort should promote such investigations, whenever a post-coital chronology is suggested. The good clinical pertinence of positive skin tests must be emphasized. Although type I hypersensitivity to semen is documented in the literature, with easy detection of specific IgE, delayed type 2 allergy presents as an as yet under-diagnosed etiology of post-coital vulvitis. Patch tests may help to confirm that contact dermatitis may be due to seminal proteins.

omega-[(4,6-Diphenyl-2-pyridyl)oxy]alkanoic acid derivatives: a new family of potent and orally active LTB4 antagonists.

A series of omega-[(4,6-diphenyl-2-pyridyl)oxy]alkanoic acid derivatives was prepared which inhibited the binding of leukotriene B4 to its receptors on guinea pig spleen membranes and on human polymorphonuclear leukocytes (PMNs) and selectively antagonized the LTB4-induced elastase release in human PMNs. On the basis of these three screens, a structure-activity relationship was investigated. alpha-Substitution on the carboxylic acid side chain led to only small changes in the binding affinities but greatly enhanced the LTB4 antagonist activity. Substitution on the phenyl rings was also evaluated. The terminal carboxylic acid function can be replaced by a tetrazole ring without loss in activity. The best in vitro LTB4 antagonists of this series were investigated in vivo in the inhibition of LTB4-induced leukopenia in rabbits. Compound 9b (RP69698) displayed potent LTB4 antagonist activity, after oral administration, with an ED50 value of 6.7 mg/kg.

Effects of beta 2-adrenoceptor agonists on anti-IgE-induced contraction and smooth muscle reactivity in human airways.

1. The beta 2-adrenoceptor agonists, salbutamol, salmeterol and RP 58802 relaxed basal tone of human isolated bronchial smooth muscle. Salmeterol- and RP 58802-induced relaxations persisted for more than 4 h when the medium was constantly renewed after treatment. 2. Salbutamol, salmeterol and RP 58802 reversed histamine-induced contractions in human airways (pD2 values: 6.15 +/- 0.21, 6.00 +/- 0.19 and 6.56 +/- 0.12, respectively). 3. Anti-IgE-induced contractions were significantly inhibited immediately after pretreatment of preparations with beta 2-adrenoceptor agonists (10 microM). However, when tissues were treated with beta 2-agonists and then washed for a period of 4 h, salmeterol was the only agonist which significantly inhibited the anti-IgE response. 4. Histamine response curves were shifted to the right immediately after pretreatment of tissues with the beta 2-adrenoceptor agonists (10 microM; 20 min), but maximal contractions were not affected. After a 4 h washing period, the histamine curves were not significantly different from controls. Concentration-effect curves to acetylcholine (ACh) or leukotriene C4 (LTC4) were not significantly modified after beta 2-agonist pretreatment. 5. These results suggest that beta 2-adrenoceptor agonists may prevent anti-IgE-induced contraction by inhibition of mediator release rather than alterations of those mechanisms involved in airway smooth muscle contraction.

Natural history of sensitizations in atopic dermatitis. A 3-year follow-up in 250 children: food allergy and high risk of respiratory symptoms.

BACKGROUND AND DESIGN: The aim of the study was to define the natural history of sensitization in atopic dermatitis (AD) through cross-sectional (comparison of three age classes) and longitudinal study: 250 children with minor (32.5%), moderate (32.5%), and severe (35%) AD were examined for aeroallergen and food hypersensitivity (skin tests, clinical scoring after allergen elimination, and food challenges). RESULTS: The allergic screening was negative in minor AD and positive in 33% of cases of moderate AD that were concerned with aeroallergen sensitizations with only limited respiratory involvement. This suggests that nonspecific cutaneous hyperreactivity remains an almost exclusive precipitating factor in moderate or minor AD. Severe AD was characterized by a positive allergologic assessment in 100% of patients: food allergens were incriminated as flare factors in 96% of patients, with associated aeroallergen sensitization in 36%. Even at a young age (less than or equal to 2 years), the severe AD group is marked by an extreme frequency of food sensitization (93%) that persists in 73% of children younger than 7 years and 67% younger than 16 years. From the comparison of three age classes, the sequence of food and respiratory sensitization seems to be part of the natural course of AD. Prospective study in 29 children of group 1 (less than 2 years) with a 3-year follow-up confirms the data of the cross-sectional study since 27 had development of aeroallergen sensitization, with respiratory symptoms as early as age 3 years in 23 of these children. CONCLUSION: The detection of food allergy in a child presenting with AD is likely to indicate a prognosis of severe AD and should be considered by dermatologists as a potentially important predictor of further respiratory symptoms.

[Creole dyschromia or idiopathic macular hypomelanosis of the melanodermic halfcast of Guillet-Hélénon]. / Dyschromie créole ou hypomélanose maculeuse idiopathique du métis mélanoderme de Guillet-Hélénon.

Melanodermic halfcasts may develop an original cutaneous dyschromia known as "progressive and extensive hypomelanosis" (Guillet-Helenon 1988). This disease is characterized by hypochromic and coalescent macules on the back and abdomen with possible spontaneous improvement within five years, favoured by UV exposure. The disease is not restricted to a limited geographic group: eight observations were collected in melanodermic patients leaving in temperate area. The pathogenesis of the disorder involves a variation in melanosome size and distribution with decrease in production of type IV melanosomes featuring a change of ultrastructural phenotype of melanogenesis. Since it may be misdiagnosed as fungal disease, leprosy or achromic eczema leading to useless laboratory examinations, this specific and frequent disease deserves to be known and recognized.

[Darier-Ferrand dermatofibrosarcoma in children]. / Dermatofibrosarcome de Darier-Ferrand de l'enfant.

BACKGROUND: Dermatofibrosarcoma is a tumor relatively ignored in childhood. CASE REPORT: A 11 year-old boy was referred because he suffered from a tumor of the neck, which had progressively developed after a cervical traumatism occurring 4 years earlier. Examination showed a tumor moderately infiltrated, attached to the overlying erythematous skin. Biopsy showed ill-limited dermal and hypodermal proliferation of fusiform cells with a storiform arrangement. Two successive excisions were necessary and the patient is well 2 years later. CONCLUSION: This case confirms responsibility of previous traumatism, progressiveness of course and necessity of large excision.

[Pachydermodactyly in adolescents: a sign of discomfort?]. / Pachydermodactylie de l'adolescent: expression d'un mal-être?

BACKGROUND: Pachydermodactyly is an acquired dermatosis related to psychological disturbances. CASE REPORT: A 16 year-old boy presented with fibrous skin hypertrophy of proximal interphalangeal joint areas of both hands suggestive of pachydermodactyly. Skin biopsy confirmed the fibromatous nature of hypertrophy. The personal history of the child confirmed that pachydermocactyly was due to compulsive rubbing stretching movements in a patient with psychological troubles. CONCLUSIONS: Pachydermodactyly, mainly observed among male teenagers, must be considered as an induced dermatosis and distinguished from primary fibromatosis.

[Contact urticaria to natural rubber latex in childhood and associated atopic symptoms: a study of 27 patients aged under 15 years]. / Atopie et urticaire de contact au latex chez l'enfant. Etude chez 27 malades de moins de 15 ans.

BACKGROUND: Although natural rubber latex hypersensitivity is considered as a major problem in adult, it may be still misdiagnosed in childhood. PATIENTS AND METHOD: We collected 27 observations of natural rubber latex contact urticaria in children under 15 Years of age, 21 of them aged under 8. RESULTS: All of them where atopic and 19 out of 27 presented with other association paroxystic signs of immediate hypersensitivity, that were lately related to latex allergy (i. e. asthma, rhinitis, conjunctivitis, fainting). Cross-allergy to food allergens was present in 33 p. 100. Average level of specific IgE to natural rubber latex was 21.7 kU/l. One to 4 Years follow up confirmed the benefit of latex eviction on urticaria as well as on associated symptoms. It led to the early detection of ficus allergy in 4 of them. DISCUSSION: This series confirms that atopy is at high risk for natural rubber latex allergy in children. These data suggest that atopic children are exposed too early to latex devices such as pacifiers, toodles of latex toys. Contact urticaria in children must be considered as a possible marker of other respiratory or general symptoms that may have been misconsidered under other etiologies.

[Allergologic survey in 251 patients with moderate or severe dermatitis. Incidence and value of the detection of contact eczema, food allergy or sensitization to air-borne allergens]. / Enquête allergologique chez 251 malades atteints de dermatite atopique modérée ou sévère. Fréquence et intérêt du dépistage de l'eczéma de contact, de l'allergie alimentaire et de la sensibilisation aux aéroallergènes.

INTRODUCTION: Because of the increased recruitment of uncontrolled atopic dermatitis (AD) necessitating chronic use of dermocorticosteroids, we developed a prospective allergologic survey in a serie of 251 patients presenting with moderate or severe AD. PATIENTS AND METHOD: 251 patients were refered for allergologic assessment and followup. The clinical severity was assessed by use of standardized scores. Patients were grouped by age: group 1 (70 children younger than 2 years), group 2 (93 children between 2 and 7 years), group 3 (23 children between 7 and 15 years), group 4 (65 children over 15 years and adults). All the patients were systematically screened for contact dermatitis and IgE mediated sensitization (inhallant and food allergens) with blood tests for IgE, prior to evaluation of clinical relevance. RESULTS: Aero-allergen sensitization was demonstrated in 51 p. 100 of children and 89 p. 100 of adults. It was present earlier in severe AD with main clinical involvement for nose and throat and respiratory symptoms. Clinical responsibility for dermatitis was documented in only 6 p. 100 of AD. Food allergy was early incriminated as flare factors in most of severe AD (96 p. 100 of children and 81 p. 100 of adults) with major and persistant improvement under eviction diet. Main allergens were eggs (46 p. 100), pea-nuts (29 p. 100), shellfish (24 p. 100), milk (20 p. 100), flour (14 p. 100), fish (14 p. 100), soybeans (8.9 p. 100). Food allergy to yeasts (7.2 p. 100) was important in adults. Food allergy is the earliest allergy in the course of severe AD and the number of involved trophallergens increases in older patients. Patch tests were positive in 40 p. 100 of patients (i. e. 31 p. 100 of children and 66 p. 100 of adults) with a greater incidence in moderate AD. Main allergens were metals (54 p. 100), fragrances (19 p. 100), balsam of Peru (10 p. 100), parabens (8 p. 100) and lanoline (4 p. 100). CONCLUSION: When AD is not efficiently controlled by dermocorticosteroids, allergologic screening and treatment of children and adults proves to be very interesting. Specific measures regarding food allergy and contact dermatitis reduce or vanish cutaneous flares. As for inhallant sensitizations, Dermatologists should be awared that they may play a role regarding assessment of sensitization and prevention of respiratory symptoms in moderate and severe AD since the risk of complications is important in both groups.

[Facial myofibroma of the newborn simulating sarcoma]. / Présentation sarcomateuse d'un myofibrome facial du nouveau-né.

INTRODUCTION: Myofibromatosis is a rare but probably under estimated tumor. OBSERVATION: We report a case of a newborn presenting with a facial tumor suggestive of sarcoma. Discrepancy between clinical features and histologic pattern of angioma suggested the diagnosis of myofibroma. The diagnostic of myofibromatosis was made later by specific labelling (actin-smooth muscle) and was confirmed by major spontaneous involution. DISCUSSION: The histology of myofibroma associates fibrous and angiomatous patterns that may be confusing when examining a small biopsy. Due to confusing semiology and histology, subcutaneous myofibromas are certainly misdiagnosed and specific actin labelling (actin, HHF 35) may be of interest. Myofibromas are the most frequent tumor among fibromatoses. The diagnosis should be suspected on the stony consistence of the tumor uncompatible with angiomatous histology. Contrary to multicentric myofibromas of which the prognosis depends on visceral involvement and compressions (72 p. 100 of fatal outcome), solitary subcutaneous myofibroma has a very good prognosis with spontaneous involution.

[Dermatitis caused by the manchineel tree]. / La dermite du mancenillier.

Contact dermatitis form Hippomane mancinella L. (manchineel) is commonly observed in Caribbean and Central American Coast land. Its sap from leaf exudate and from the fruit induce severe dermatitis that may involve oral, ocular, genital mucous membranes and skin, depending on the mediate or direct type of contact. Intense itching or burning sensation occurs within an hour and is followed by painful erythema, vesicles, bullae or pustulae, the latter being highly suggestive of mancheneel. Oropharyngeal and ocular lesions may by very severe. The brief delay and the burnlike appearance of the lesions suggest an orthoergic mechanism due to a caustic that could be similar to the substance identified in an other species of Euphorbiacae as phorbol esters. Traditional and native remedies are presented herein.

[Darier's erythema annulare centrifugum of neonatal onset with a 15 years' follow-up. Efficacy of interferon and role of cytokines]. / Erythème annulaire centrifuge de darier à ddebut néonatal avec 15 ans de suivi. Efficacité de l'interféron et rôle de cytokines.

INTRODUCTION: Darier's erythema annulare centrifugum (EAC) is a disease of unknown etiology. Some observations of EAC in infancy suggest a better prognosis for early EA. The observations presented herein gives different information regarding prognosis and pathogenesis. OBSERVATION: A child presents with typical lesions of EAC from early infancy up to the age of 15 years. Laboratory data are normal. Similar lesions were locally reproduced by intradermal injection by candidine but antifungal drugs were unsuccessful. Many antiinflammatory treatments failed to improve the disease. Because of the improvement during hyperthermic episodes, a treatment by subcutaneous interferon alpha (2 millions U 3 times a week) was given for six months with a dramatic success (with seric increase of TNF alpha and IL2) DISCUSSION: The long term duration of EAC suggests that EA of infancy may represent the early beginning of Darier's EAC. The efficacy of interferon suggests that cytokines are involved in the pathogenesis of EAC.

[Netherton's syndrome. Current aspects. Apropos of 9 cases]. / Syndrome de Netherton. Aspects actuels. A propos de neuf cas.

Data concerning 9 cases of Netherton's syndrome (NS) have been collected from 6 French dermatology units (table I). Analysis of these data has confirmed the information previously published, notably the prevalence of congenital ichthyosis erythroderma (CIE) as cutaneous manifestation in the neonatal period (77 p. 100), hair shaft dysplasia being rarely found at that stage (11 p. 100). In the majority of cases (5/9 in our series), CIE evolves in adults as ichthyosis linearis circumflexia (ILC), with trichorrhexis invaginata (TI) as the predominant hair shaft dysplasia. These data are in agreement with the diagnostic elements laid down by Dupré and Traupe. Some points may have been underestimated in the past. They include: hypernatraemic dehydration in the neonate; short stature and low weight (unrelated to endocrine disorders; mental and neurological retardation possibly associated with seizures. Various manifestations of hypersensitivity have been noted in 26 p. 100 of the published cases and in 6 of our 9 patients. The aggravating role played by hypersensitivity may be considered in some cases. NS must be regarded as a broad-spectrum disease the margins of which could be isolated skin manifestations in ILC and ichthyosis erythroderma with various associated disorders in cases with severe illness.

[Progressive and confluent hypomelanosis of the melanodermic metis]. / Hypomélanose maculeuse confluente et progressive du métis mélanoderme.

Melanodermic half-castes may develop a progressive and extensive hypomelanosis presenting as an original skin condition. The course of the disease is characteristic: it occurs mainly in females from 18 to 25 years of age with a progressive development of hypochromic and coalescent macules on the back and abdomen. This disease may regress spontaneously within 5 years and healing seems to be facilitated by UV exposure. Decreased epidermal melanin is the only histological feature. Ultrastructural examination has led to characterize this bizarre disease by a switch from stage IV single melanosomes negroid type to small type I-III aggregated melanosomes (caucasoid phenotype of melanogenesis). Although the pathogenesis of the disorder remains obscure, it may be stated that the variation in skin coloration in these patients is due to a variation in melanosome size and distribution. It is possible that this variation is due to a decrease in production of type IV melanosomes and that this apparent change of ultrastructural phenotype represent the consequence of a simple imbalance in melanosomes production favoring small I to III melanosomes. This disease is not restricted to a limited geographic group: it is present in melanodermic half-castes of different areas and therefore deserves to be known and recognized.