Prévention des adhérences péricardiques avec une membrane biorésorbable [Prevention of pericardial adhesions with a bioresorbable membrane]

A bioresorbable membrane made of sodium hyaluronate and carboxymethycellulose, has been reported to prevent peritoneal adhesion. This study was designed to test its efficiency in the prevention of pericardial adhesions. Two groups of six pigs (mean weight 72 +/- 8 kg) were chosen for the experiment. The heart was exposed through a left thoracotomy and a wide patch of pericardium was excised. In the test group (n = 6), the left ventricular area without pericardium was divided into two areas: area A where six stitches of Prolene were performed, and area B which was left intact. The membrane was applied on the both areas as well as on the adjacent area covered with pericardium (area C). In the control group (n = 6), the same protocol was performed except for the membrane application. The animals were sacrificed one month later. The adhesion status as well as the visibility of the coronary anatomy was assessed according to severity scores ranging from 0 to 3 for the adhesions and from 0 to 2 for the visibility. The difference between groups was considered significant when p < 0.05. The adhesion score of the area A was 1.7 +/- 0.5 in the test group versus 2.5 +/- 0.5 in the control group (p = 0.02) and the visibility score was 1.3 +/- 0.8 and 2 +/- 0 respectively (p = 0.07). In the area B, the adhesion score was 1 +/- 0 in the test group versus 2 +/- 0.6 in the control group (p = 0.03) and the visibility score was 0.7 +/- 0.5 and 2 +/- 0 respectively (p = 0.001). Lastly, in the area C, the adhesion score was 1 +/- 0 in both groups (n.s.) and the visibility score was 0.7 +/- 0.4 in the test group versus 0.5 +/- 0.5 in the control group (n.s.). In this animal model, the role of the bioresorbable membrane in the prevention of pericardial adhesions is limited to the areas without pericardial cover and without foreign material. The presence of foreign material neutralizes its effect.

Characterization of an interaction between fetal hemoglobin and lipid A of LPS resulting in augmented induction of cytokine production in vivo and in vitro.

A previously described extract of sheep fetal liver was reported to reverse many of the cytokine changes associated with aging in mice, including an augmented spleen cell ConA-stimulated production of IL-4 and decreased production of IL-2. Similar effects were not seen with adult liver preparations. These changes were observed in various strains of mice, including BALB/c, DBA/2 and C57BL/6, using mice with ages ranging from 8 to 110 weeks. Preliminary characterization of this crude extract showed evidence for the presence of Hb gamma chain, as well as of lipid A of LPS. We show below that purified preparations of sheep fetal Hb, but not adult Hb, in concert with suboptimally stimulating doses of LPS (lipid A), cooperate in the regulation of production of a number of cytokines, including TNFalpha and IL-6, in vitro. Furthermore, isolated fresh spleen or peritoneal cells from animals treated in vivo with the same combination of Hb and LPS, showed an augmented capacity to produce these cytokines on further culture in vitro. Evidence was also obtained for a further interaction between CLP, LPS and fetal Hb itself in this augmented cytokine production. These data suggest that some of the functional activities in the fetal liver extract reported earlier can be explained in terms of a novel immunomodulatory role of a mixture of LPS (lipid A) and fetal Hb.

Fibrosi retroperitoneal : descripció de les característiques clinicopatològiques, tractament i evolució. Revisió restrospectiva de 16 casos

La fibrosi retroperitoneal peritoneal és una entitat clínica infreqüent,l’etiologia roman desconeguda en 2/3 dels casos. Es una inflamació crònica amb fibrosi del teixit retroperitoneal envoltant grans vasos, urèters i òrgans abdominals. Actualment el pronòstic ha millorat amb el tractament immunosupressor i la cirurgia. Presentem una revisió dels pacients diagnosticats en el nostre centre de FRP idiopàtica amb l’objectiu de revisar les característiques clíniques, l’afectació orgànica, troballes de laboratori i radiològiques, el tractament rebut i el seguiment de l’evolució clínica. El tractament va ser la corticoteràpia acompanyada de cirurgia. En el seguiment posterior, les recidives van ser freqüents.

Dialyse et écologie: est-il possible de faire mieux à l'avenir [Dialysis and ecology: can we do better in the future?].

Development of dialysis has saved the lives of many patients. However, haemodialysis and peritoneal dialysis are very demanding in resources such as water and electricity, and generate a large amount of waste. In this article, we will review the environmental aspects of dialysis. Different solutions will be discussed, such as recycling of water discharged during reverse osmosis, the integration of solar energy, recycling of waste plastics, and the use of other techniques such as sorbent dialysis. In a world where natural resources are precious and where global warming is a major problem, it is important that not only dialysis, but all branches of medicine become more attentive to ecology.

The neutrophil NLRC4 inflammasome selectively promotes IL-1β maturation without pyroptosis during acute Salmonella challenge.

The macrophage NLRC4 inflammasome drives potent innate immune responses against Salmonella by eliciting caspase-1-dependent proinflammatory cytokine production (e.g., interleukin-1β [IL-1β]) and pyroptotic cell death. However, the potential contribution of other cell types to inflammasome-mediated host defense against Salmonella was unclear. Here, we demonstrate that neutrophils, typically viewed as cellular targets of IL-1β, themselves activate the NLRC4 inflammasome during acute Salmonella infection and are a major cell compartment for IL-1β production during acute peritoneal challenge in vivo. Importantly, unlike macrophages, neutrophils do not undergo pyroptosis upon NLRC4 inflammasome activation. The resistance of neutrophils to pyroptotic death is unique among inflammasome-signaling cells so far described and allows neutrophils to sustain IL-1β production at a site of infection without compromising the crucial inflammasome-independent antimicrobial effector functions that would be lost if neutrophils rapidly lysed upon caspase-1 activation. Inflammasome pathway modification in neutrophils thus maximizes host proinflammatory and antimicrobial responses during pathogen challenge.

Identification and modelling of human breast cancer subtypes

Résumé Le cancer du sein est le cancer le plus commun chez les femmes et est responsable de presque 30% de tous les nouveaux cas de cancer en Europe. On estime le nombre de décès liés au cancer du sein en Europe est à plus de 130.000 par an. Ces chiffres expliquent l'impact social considérable de cette maladie. Les objectifs de cette thèse étaient: (1) d'identifier les prédispositions et les mécanismes biologiques responsables de l'établissement des sous-types spécifiques de cancer du sein; (2) les valider dans un modèle ín vivo "humain-dans-souris"; et (3) de développer des traitements spécifiques à chaque sous-type de cancer du sein identifiés. Le premier objectif a été atteint par l'intermédiaire de l'analyse des données d'expression de gènes des tumeurs, produite dans notre laboratoire. Les données obtenues par puces à ADN ont été produites à partir de 49 biopsies des tumeurs du sein provenant des patientes participant dans l'essai clinique EORTC 10994/BIG00-01. Les données étaient très riches en information et m'ont permis de valider des données précédentes des autres études d'expression des gènes dans des tumeurs du sein. De plus, cette analyse m'a permis d'identifier un nouveau sous-type biologique de cancer du sein. Dans la première partie de la thèse, je décris I identification des tumeurs apocrines du sein par l'analyse des puces à ADN et les implications potentielles de cette découverte pour les applications cliniques. Le deuxième objectif a été atteint par l'établissement d'un modèle de cancer du sein humain, basé sur des cellules épithéliales mammaires humaines primaires (HMECs) dérivées de réductions mammaires. J'ai choisi d'adapter un système de culture des cellules en suspension basé sur des mammosphères précédemment décrit et pat décidé d'exprimer des gènes en utilisant des lentivirus. Dans la deuxième partie de ma thèse je décris l'établissement d'un système de culture cellulaire qui permet la transformation quantitative des HMECs. Par la suite, j'ai établi un modèle de xénogreffe dans les souris immunodéficientes NOD/SCID, qui permet de modéliser la maladie humaine chez la souris. Dans la troisième partie de ma thèse je décris et je discute les résultats que j'ai obtenus en établissant un modèle estrogène-dépendant de cancer du sein par transformation quantitative des HMECs avec des gènes définis, identifiés par analyse de données d'expression des gènes dans le cancer du sein. Les cellules transformées dans notre modèle étaient estrogène-dépendantes pour la croissance, diploïdes et génétiquement normales même après la culture cellulaire in vitro prolongée. Les cellules formaient des tumeurs dans notre modèle de xénogreffe et constituaient des métastases péritonéales disséminées et du foie. Afin d'atteindre le troisième objectif de ma thèse, j'ai défini et examiné des stratégies de traitement qui permettent réduire les tumeurs et les métastases. J'ai produit un modèle de cancer du sein génétiquement défini et positif pour le récepteur de l'estrogène qui permet de modéliser le cancer du sein estrogène-dépendant humain chez la souris. Ce modèle permet l'étude des mécanismes impliqués dans la formation des tumeurs et des métastases. Abstract Breast cancer is the most common cancer in women and accounts for nearly 30% of all new cancer cases in Europe. The number of deaths from breast cancer in Europe is estimated to be over 130,000 each year, implying the social impact of the disease. The goals of this thesis were first, to identify biological features and mechanisms --responsible for the establishment of specific breast cancer subtypes, second to validate them in a human-in-mouse in vivo model and third to develop specific treatments for identified breast cancer subtypes. The first objective was achieved via the analysis of tumour gene expression data produced in our lab. The microarray data were generated from 49 breast tumour biopsies that were collected from patients enrolled in the clinical trial EORTC 10994/BIG00-01. The data set was very rich in information and allowed me to validate data of previous breast cancer gene expression studies and to identify biological features of a novel breast cancer subtype. In the first part of the thesis I focus on the identification of molecular apacrine breast tumours by microarray analysis and the potential imptìcation of this finding for the clinics. The second objective was attained by the production of a human breast cancer model system based on primary human mammary epithelial cells {HMECs) derived from reduction mammoplasties. I have chosen to adopt a previously described suspension culture system based on mammospheres and expressed selected target genes using lentiviral expression constructs. In the second part of my thesis I mainly focus on the establishment of a cell culture system allowing for quantitative transformation of HMECs. I then established a xenograft model in immunodeficient NOD/SCID mice, allowing to model human disease in a mouse. In the third part of my thesis I describe and discuss the results that I obtained while establishing an oestrogen-dependent model of breast cancer by quantitative transformation of HMECs with defined genes identified after breast cancer gene expression data analysis. The transformed cells in our model are oestrogen-dependent for growth; remain diploid and genetically normal even after prolonged cell culture in vitro. The cells farm tumours and form disseminated peritoneal and liver metastases in our xenograft model. Along the lines of the third objective of my thesis I defined and tested treatment schemes allowing reducing tumours and metastases. I have generated a genetically defined model of oestrogen receptor alpha positive human breast cancer that allows to model human oestrogen-dependent breast cancer in a mouse and enables the study of mechanisms involved in tumorigenesis and metastasis.

Identificação de contaminação bacteriana no sabão líquido de uso hospitalar

O estudo realizou a análise bacteriológica de sabões líquidos utilizados para lavagem das mãos dos profissionais de saúde. Trata-se de estudo exploratório transversal, desenvolvido nas unidades de internação de hospital de médio porte em Fortaleza/CE. Os dados foram colhidos no período de maio a julho de 2007. Do total de 59 frascos com sabão líquido, 33 continham os seguintes microorganismos: Burkholderia cepacia (n=14), Pseudomonas putidas (9), Pseudomonas aeruginosa (3), Klebsiella pneumoniae (3), Enterobacter cloacae (2), Pseudomonas luteola (2). As unidades com maior número de amostras contaminadas foram a clínica cirúrgica (n=7) e a clínica dermatológica (n=4). A contaminação também foi verificada em frasco original do mesmo lote de sabão líquido usado para abastecer as saboneteiras. Podemos concluir ser necessário disciplinar e controlar a qualidade desses produtos nas linhas de produção tanto quanto nas fases de uso nos serviços de saúde, sobretudo porque sua utilidade se presta à prevenção de infecção hospitalar.

Colchões do tipo caixa de ovo: um reservatório de Staphylococcus aureus resistente à meticilina?

O estudo teve como objetivo avaliar as condições microbiológicas de colchões caixa de ovo em uso hospitalar com a finalidade de identificar a presença de Staphylococcus aureus e seu fenótipo de resistência à meticilina (MRSA). Coletaram-se as amostras microbiológicas nos colchões por meio de placas de contato PetrifilmTM em posições pré-estabelecidas. Totalizou-se 180 placas coletadas em 15 colchões, das quais 139 (72,2%) foram positivas para Staphylococcus aureus. Desse total, 77 (55,4%) e 62 (44,6%) corresponderam respectivamente à coleta antes e após a lavagem dos colchões. Evidenciou-se redução significante (p=0,023) das Unidades Formadoras de Colônias (UFC), entretanto com relação ao perfil de resistência foi identificado 8 (53,3%) colchões com MRSA. Diante dos resultados, pode-se inferir sobre o risco destes colchões atuarem como reservatórios secundários na cadeia de infecção, especialmente no que se refere à presença de MRSA.

Eficácia de três métodos de degermação das mãos utilizando gluconato de clorexidina degermante (GCH 2%)

A degermação cirúrgica das mãos e dos antebraços é um procedimento que integra as atividades de paramentação cirúrgica como uma medida de prevenção de infecção do sítio cirúrgico. Com o advento dos princípios antissépticos degermantes, a necessidade do uso de escovas para a degermação cirúrgica tem sido questionada e recomendado o abandono deste uso devido às lesões provocadas na pele. Com a finalidade de fundamentar a eficácia da técnica da degermação cirúrgica sem o uso de escovas ou esponjas, o objetivo deste estudo foi avaliar três métodos para degermação cirúrgica utilizando a formulação degermante de gluconato de clorexidina - GCH 2%: com escova, com esponja e sem artefato. Foram avaliados 29 profissionais da saúde, utilizando o método de caldo de luva para coleta de micro-organismos antes e depois de cada método testado. As análises estatísticas comprovaram não haver diferenças estatísticas significantes na redução microbiana entre os três métodos analisados (p=0,148), o que teoricamente descarta a necessidade da continuidade do uso de escovas e esponjas para a realização da degermação das mãos.

Les anticorps monoclonaux radiomarqués en tant que missiles anti-tumeurs, leurs succès diagnostiques, leur potentiel thérapeutique

While it is now well accepted that radiolabeled antibodies can be useful for tumour detection by immunoscintigraphy, the use of larger doses of more aggressive radioisotopes coupled to antibodies for radioimmunotherapy is still in its infancy. At the experimental level, our group has shown that the intravenous injection of large doses of 131I labeled F(ab')2 fragments from monoclonal anti-carcinoembryonic antigen (CEA) antibodies can eradicate well established human colon carcinoma xenografts in nude mice. At the clinical level, in a dosimetry study performed at the Institut Gustave Roussy, the same anti-CEA monoclonal antibodies and fragments, labeled with subtherapeutic doses of 131I, were injected in patients with liver metastases from colorectal carcinomas. Direct measurement of radioactivity in surgically resected liver metastases and normal liver confirmed the specificity of tumour localization of the antibodies, but also showed that the calculated radiation doses which could be delivered by injections of 200 to 300 mCi of 131I labeled antibodies or fragments, remained fairly low, in the range of 1,500 to 3,000 rads. This is obviously insufficient for a single modality treatment. An alternative approach is to inject radiolabeled antibodies intra peritoneally to treat peritoneal carcinomatosis. Several clinical studies using this strategy are presently under evaluation and suggest that positive results can be obtained when the tumour diameters are very small. In systemic radioimmunotherapy, positive results have been obtained in more radiosensitive types of malignancies such as B cell lymphomas by intravenous injection of antibodies directed against B cell differentiation markers or against idiotypic antigens from each lymphoma, and labeled with 131I or 90Y. The major directions of research for improvement of radioimmunotherapy include the design of genetically engineered new forms of humanized antibodies, the synthesis of original chelates for coupling new radioisotopes to antibodies and the development of two step strategies for immunolocalization of radioisotopes.

Phenotypes influencing low physical activity in maintenance dialysis.

OBJECTIVE: The "Pas à Pas" initiative aimed at evaluating the weekly physical activity (PA) and its determinants in a large cohort of dialysis patients. SETTING: Physical inactivity is a risk factor for mortality in maintenance dialysis patients and is still poorly documented in this population. DESIGN: A prospective national epidemiological study was performed. SUBJECTS: A total of 1,163 patients on maintenance dialysis (hemodialysis and peritoneal dialysis) were included. INTERVENTION AND MAIN OUTCOME MEASURE: PA was recorded during seven consecutive days using a pedometer to measure daily step numbers. RESULTS: Median age was 63 years (Q1 51-Q3 75). Sixty-three percent were sedentary (<5000 steps/day) with a median of 3,688 steps/day (1,866-6,271)]. PA level was similar between hemodialysis patients and those on peritoneal dialysis (3,693 steps [1,896-6,307] vs. 3,320 [1,478-5,926], P = .33). In hemodialysis patients, PA was lower on dialysis days compared with nondialysis days (2,912 [1,439-5,232] vs. 4,054 [2,136-7,108], respectively, P < .01). PA gradually decreased with age, 57% being sedentary between 50 and 65 years and 83% of patients after 80 years. Beyond this age effect, we identified, for the first time, specific phenotypes of patients with lower PA, such as inflammation, cardiovascular disease, protein energy wasting, obesity, and diabetes. By contrast, previous kidney transplantation and a higher muscle mass were associated with higher PA. CONCLUSIONS: Dialysis patients present a very low level of PA with high sedentary. Acting on patient's modifiable phenotypes may help to increase PA to improve morbidity, mortality, and quality of life.

Revisão sistemática sobre antissepsia cirúrgica das mãos com preparação alcoólica em comparação aos produtos tradicionais

A antissepsia cirúrgica das mãos visa à prevenção de infecções do sítio cirúrgico, importante causa de morbimortalidade pós-operatória e aumento dos custos hospitalares. Este estudo teve como objetivo comparar a eficácia de preparações alcoólicas com os produtos tradicionais na antissepsia cirúrgica das mãos por meio de uma revisão sistemática da literatura. Foram considerados estudos primários ou secundários, tendo como desfecho a contagem microbiana das mãos ou taxas de infecções do sítio cirúrgico. A busca foi realizada no Portal BVS, PubMed, Ask e MEDLINE. Foram selecionados 25 estudos (2 revisões sistemáticas, 19 experimentais e 4 de coorte). As preparações alcoólicas tiveram uma redução microbiana igual e/ou maior aos produtos tradicionais em 17 estudos e inferior em 4; as taxas de infecções do sítio cirúrgico foram similares. Portanto, existem evidências científicas que suportam a segurança das preparações alcoólicas para antissepsia cirúrgica das mãos.

Metastatic tumors to the colon and rectum: a multi-institutional study.

Context.-Unlike the small bowel, the colorectal mucosa is seldom the site of metastatic disease. Objective.-To determine the incidence of truly colorectal metastases, and subsequent clinicopathologic findings, in a substantial colorectal cancer population collected from 7 European centers. Design.-During the last decade, 10 365 patients were identified as having colorectal malignant tumors, other than systemic diseases. Data collected included patient demographics, clinical symptoms, treatment, the presence of metastases in other sites, disease-free interval, follow-up, and overall survival. All secondary tumors resulting from direct invasion from malignant tumors of the contiguous organs were excluded, as well as those resulting from lymph node metastases or peritoneal seeding. Results.-Only 35 patients were included (10 men) with a median age of 59 years. They presented with obstruction, bleeding, abdominal pain, or perforation. The leading source of metastases was the breast, followed by melanoma. Metastases were synchronous in 3 cases. The mean disease-free interval for the remaining cases was 6.61 years. Surgical resection was performed in 28 cases. Follow-up was available for 26 patients; all had died, with a mean survival time of 10.67 months (range, 1-41 months). Conclusions.-Colorectal metastases are exceptional (0.338%) with the breast as a leading source of metastases; they still represent a late stage of disease and reflect a poor prognosis. Therefore, the pathologist should be alert for the possibility of secondary tumors when studying large bowel biopsies. Any therapy is usually palliative, but our results suggest that prolonged survival after surgery and complementary therapy can be obtained in some patients.

Antioxidant protection of statins in acute kidney injury induced by sepsis

Objective Evaluating the effect of preconditioning with simvastatin in acute kidney injury induced by sepsis. Method Male adult Wistar rats were divided into the following groups: SHAM (control); SHAM+Statin (0.5 mg/kg simvastatin, orally); Sepsis (cecal puncture ligation – CPL); Sepsis+Statin. Physiological parameters, peritoneal fluid culture, renal function, oxidative metabolites, severity of acute kidney injury and animal survival were evaluated. Results The treatment with simvastatin in induced sepsis showed elevation of creatinine clearance with attenuation of generation of oxidative metabolites, lower severity of acute kidney injury and reduced mortality. Conclusion This investigation confirmed the renoprotection with antioxidant principle of the simvastatin in acute kidney injury induced by sepsis in an experimental model.

La tuberculose extrapulmonaire [Extrapulmonary tuberculosis].

Extrapulmonary tuberculosis represents an increasing proportion of all cases of tuberculosis reaching 20 to 40% according to published reports. Extrapulmonary TB is found in a higher proportion of women, black people and immunosuppressed individuals. A significant proportion of cases have a normal chest X-Ray at the time of diagnosis. The most frequent clinical presentations are lymphadenitis, pleuritis and osteoarticular TB. Peritoneal, urogenital or meningeal tuberculosis are less frequent, and their diagnosis is often difficult due to the often wide differential diagnosis and the low sensitivity of diagnostic tests including cultures and genetic amplification tests. The key clinical elements are reported and for each form the diagnostic yield of available tests. International therapeutic recommendations and practical issues are reviewed according to clinical presentation.