[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.

[Measles in pregnancy: a review]. / Rougeole chez la femme enceinte : mise au point.

Although measles is usually considered a benign viral disease of childhood, people may be affected whatever their age with severe pneumologic or neurologic consequences are more frequent before 5 years old and after 20 years old. The consequences of a congenital measles, defined as a newborn eruption within 10 days after birth, can be dramatic. The incidence of measles has significantly decreased since first vaccines were introduced in the late 1960s. In France, active immunization for measles is proposed since 1983. Since the beginning of 2008, France has been experiencing a measles outbreak with more than 17,000 notified cases. The current measles outbreak affects more particularly very young children and young adults and, among these, pregnant women. Measles during pregnancy may be severe mainly due to pneumonia. Measles is associated with a risk of miscarriage and prematurity, but congenital anomalies have not been described. If rash occurs near term, the consequences of congenital measles could be severe. Prevention of measles in pregnant women is based on improving immunization coverage, currently insufficient to eradicate virus circulation. The aim of this review is to state on the latest data concerning measles virus, give latest vaccine recommendations, and also to suggest management of measles contact or measles infection during pregnancy.

[A suspected case of in utero transmission of influenza A (H1N1) 2009]. / Un possible cas de transmission in utero du virus de la grippe A (H1N1).

A 34-year-old woman consulted the day before a scheduled caesarean for dry cough. A positive rhinopharyngeal sample for PCR testing for influenza A H1N1 led to a curative oseltamivir (Tamiflu®) treatment. At delivery a direct contact between the newborn and mother lasted only few seconds. The first healthy baby boy developped dry cough with a rhinopharyngeal sample positive for A H1N1. The minimal contact between mother and child and the positive neonatal sample only four hours after birth allow to think that it is a rare case of prenatal transmission of influenza A H1N1 to the fetus.

[Stereotactic body radiation therapy (SBRT) in the treatment of liver metastases: state of the art]. / Radiothérapie en conditions stéréotaxiques des métastases hépatiques.

Liver metastases are frequently found in oncologic patients. Chemotherapy is the standard treatment in plurimetastatic patients, with the possibility to obtain a clear improvement of their prognosis. Local treatment (surgery, radiofrequency, cryotherapy, radiotherapy, etc.) could be proposed for oligometastatic patients, particularly for those with a good prognosis. Historically, radiation therapy has had a limited role in the treatment of liver metastases because of its toxicity when whole liver irradiation was delivered. Improvements in the knowledge of liver radiobiology and radiopathology as well as technical innovations in delivering radiation therapy are the basis of the modern partial liver irradiation concept. In this historical and therapeutic landscape, extracranial stereotactic radiation therapy is particularly interesting for the treatment of liver metastases. This review summarises published data on stereotactic radiotherapy for the treatment of liver metastases.

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.

[Epidemiology of patients harboring extended-spectrum beta-lactamase-producing enterobacteriaceae (ESBLE), on admission]. / Épidémiologie des patients porteurs d'entérobactéries sécrétrices de bêtalactamase à spectre élargi (EBLSE), à l'admission.

OBJECTIVE: The incidence of extended-spectrum beta-lactamase-producing enterobacteria (ESBLE) has regularly increased over the last few years. However, little is known about epidemiology of ESBLE carriers in France. The objective of this study was to determine the ESBLE carriers or infected patients profile, identified within 48 hours following hospital admission. DESIGN: This retrospective study included all patients admitted in 2006 and 2007 at the Necker-Enfants-Malades (NEM) teaching hospital, carrying or infected with ESBLE isolated within 48 hours following admission. The pediatric and adult populations were compared. RESULTS: There was no significant difference between pediatric and adult populations. Escherichia coli and Klebsiella pneumoniae were the two main species isolated, accounting respectively for 59.6 and 21.1 % of the 114 isolated strains. Among the 114 analyzed files, 24 patients (21 %) were known to be EBLSE carriers, 37 (32 %) were transferred from another hospital, including 16 from another country. Concerning the 54 (47 %) other patients, five (4 %) came from a country with high prevalence, and 44 (39 %) were treated for a chronic illness. Only five patients (4 %) carrying ESBLE did not have any usual risk factor for multidrug resistance (MDR) bacterial carriage. CONCLUSIONS: In our study, 4 % of patients carrying ESBLE admitted had no usual risk factor for MDR bacteria. Targeted screening of previous carriers, patients with chronic illness, transferred patients, or patients coming from country with high prevalence, would help to limit the spread of ESBLE.

[Pandemic influenza A H1N1 2009 flu during pregnancy: Epidemiology, diagnosis and management]. / Pandémie de grippe A H1N1 2009 et grossesse : épidémiologie, diagnostic et prise en charge.

Pandemic influenza A H1N1 2009 is a benign disease when infecting healthy adults, but it can lead to severe consequences in pregnant woman, for the fetus or its mother. The incidence of the disease is increasing strongly, and health authorities estimate that one third of the world population might be infected before the end of the winter. Diagnosis of infection with influenza virus H1N1 is suspected when a patient presents with the association of symptoms of the respiratory tract like sore throat, cough, or dyspnea, with general signs like fever, myalgias, or exhaustion. Diagnosis confirmation is obtained with nasopharyngeal swab and virus detection with molecular biology. This flu can lead to severe consequences for the pregnant woman and fetus. For this reason, it is advisable to treat pregnant women systematically by oseltamivir or zanamivir, and to treat preventively the pregnant woman in case of close contact with a suspected or confirmed infected person. Even if the management of influenza A H1N1 2009 infection during pregnancy relies on family physicians and gynecologists, every physician having in charge such cases should regularly update his knowledge regarding the evolution of the recommendations for the pandemic.

[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.

Functional compartmentalization following induction of long-term graft survival with pregraft donor-specific transfusion.

Long-term survival is achieved in rat recipients by pre-graft donor-specific blood transfusion. We characterized the immune compartments in long-term survivors and analyzed them for capacity to transfer tolerance and protect against chronic rejection. Splenocytes and spleen T cells from treated recipients transferred long-term graft survival to 100% of secondary recipients. In contrast, blood transferred graft survival to only 50% of recipients whereas blood T cells had no effect. An unaltered TCR repertoire, an increase in suppressive CD4+CD25+ T cells, a decrease in antidonor T-cell proliferative response and normal perforin-granzyme levels were the hallmarks of the spleen T cells. Blood T cells were characterized by a strongly altered CD8+ repertoire, normal CD4+CD25+ T cell number with unchanged antidonor T-cell proliferative response, an activated T-cell phenotype and an increase in perforin-granzyme levels. However, following the transfer of blood or spleen cells into secondary recipients, all grafts displayed chronic rejection. These findings provide evidence that distinct compartments play critical roles in DST recipients. Regulatory cells do not accumulate in blood, which appears to be a reservoir for cytotoxic T cells. Spleen T cells, which display a regulatory-like profile and transfer graft survival, are not able to prevent chronic rejection.

Blood T-cell repertoire in idiopathic nephrotic syndrome recurrence following kidney transplantation.

Corticosteroid resistant idiopathic nephrotic syndrome (CR-INS) is a glomerulopathy that recurs after kidney transplantation in 30-50% of patients, suggesting the involvement of systemic albuminuric factors, probably produced by activated T cells. We investigated peripheral T-cell selection and expansion before and after transplantation to identify and characterize T-lymphocyte patterns potentially associated with INS recurrence. We used a combined qualitative and quantitative assessment of Vbeta mRNA alterations at the level of the complementary determining region 3-length distribution (CDR3-LD) of the T-cell receptor (TCR). Peripheral blood mononuclear cells (PBMC) were collected from 18 CR-INS patients (8 with recurrence and 10 without recurrence) on the day of transplantation as well as at 1 month, 1 year and 5 years after transplantation, and Vbeta transcriptomes were analyzed. Our data show that blood T cells from patients with INS recurrence display a TCR repertoire that is stable in time and has a similar level of CDR3-LD alterations as the T-cell repertoire of control patients, both before and after transplantation. These results suggest that the process of INS recurrence does not involve TCR activation or specific clonal expansion of T cells. However, these results do not exclude a role for T cells in the production of an albuminuric factor.

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.

Allergic contact dermatitis from natural rubber latex in atopic dermatitis and the risk of later Type I allergy.

The aims of the study were to assess whether contact dermatitis in children could be due to a delayed hypersensitivity reaction to natural rubber latex (NRL) and to define risk factors for later occurrence of Type I hypersensitivity to this allergen. Among 1800 children investigated for contact dermatitis, 55 were referred on suspicion of rubber allergy and had patch tests to NRL, as well as prick tests and blood tests for specific immunoglobulin E (IgE). A 2-year follow-up was then carried out. Delayed hypersensitivity to NRL was confirmed in 32 children. Patch testing with NRL proved to be positive, and clinical improvement confirmed the diagnosis and relevance of patch tests. 30 of these 32 patients had associated atopic dermatitis (AD). Prick tests and blood tests for specific IgE to latex were negative at the time of diagnosis. A 2-year follow-up showed that 10 of 27 patients presenting initially with a positive patch test without associated Type I sensitization later developed immediate hypersensitivity. Children with AD are at high risk for allergy to NRL protein. Exclusion of this allergen should be strongly advised in atopics because of the dual risk of dermatitis and later evolution into severe Type I hypersensitivity.

[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.

[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.

TGF-beta1 and donor dendritic cells are common key components in donor-specific blood transfusion and anti-class II heart graft enhancement, whereas tolerance induction also required inflammatory cytokines down-regulation.

Heart allograft tolerance in adult recipients can be induced in the LEW.1W to LEW.1A congeneic strain combination by pre-graft donor-specific blood transfusion (DST). Long-term survivors accept LEW.1W graft but reject third party skin grafts. As tolerant recipients of heart allografts showed an increase in anti-donor class II antibodies, we hypothesize that these antibodies could be instrumental in tolerance induction. However, anti-donor MHC class II alone prolonged graft survival but did not induce heart allograft tolerance in this combination. We analyzed the immune response patterns in heart allograft recipients following the injection of anti-donor class II antibodies (prolongation) or DST priming (tolerance). As suggested by the different phenomena, several immunological patterns were strikingly different between the two models. In strong contrast to DST-tolerant recipients, at 5 days after transplantation, neither Th1/Th2 nor inflammatory cytokines were inhibited in recipients treated with anti-donor class II antibodies, in which only prolongation of graft survival was induced. Nevertheless, in both models, depletion of resident dendritic cells (DC) from donor hearts inhibited tolerance induction (DST) or shortened allograft survival (anti-donor class II antibodies). Moreover, TGF-beta1 was not down-regulated and administration of neutralizing anti-TGF-beta1 antibody, which inhibited tolerance induction (DST), also shortened allograft survival (anti-donor class II antibodies). These results suggest that, in these two MHC class II-restricted models, both TGF-beta1 and donor DC have a pivotal role in prolonging graft survival. However, in the days following transplantation, further inhibition of inflammatory cytokine production, particularly Th1 and macrophage-derived cytokines is required for tolerance induction.