Efficacy of oleylphosphocholine (OlPC) in vitro and in a mouse model of invasive aspergillosis.

Invasive aspergillosis (IA) has become increasingly common and is characterised by high morbidity and mortality. Upcoming resistance threatens treatment with azoles and highlights the continuous need for novel therapeutics. This laboratory study investigated the in vitro and in vivo potential of the alkylphospholipid oleylphosphocholine (OlPC) against Aspergillus.

Direct comparison of the efficacy and safety of oral treatments with oleylphosphocholine (OlPC) and miltefosine in a mouse model of L. major cutaneous leishmaniasis.

Background: Cutaneous leishmaniasis (CL) represents a range of skin diseases caused by infection with Leishmania parasites and associated with tissue inflammation and skin ulceration. CL is clinically widespread in both the Old and New World but lacks treatments that are well tolerated, effective and inexpensive. Oleylphosphocholine (OlPC) is a new orally bioavailable drug of the alkylphosphocholine family with potent antileishmanial activity against a broad range of Leishmania species/strains.

Preliminary results from a prospective study of laparoscopic aortobifemoral bypass using a clampless and sutureless aortic anastomotic technique.

Objective: This prospective study describes the feasibility and safety of a new clampless and sutureless aortic anastomotic technique used during retroperitoneal laparoscopic aortobifemoral bypass in extensive aortoiliac occlusive lesions. This is a case series of a previously published technique, demonstrating wider applicability of the technique.

Materials And Methods: Twelve patients underwent a clampless and sutureless laparoscopic bypass for TASC D aortoiliac occlusive lesions using the EndoVascular REtroperitoneoScopic Technique (EVREST).

Drug delivery by tattooing to treat cutaneous leishmaniasis.

This study establishes a proof-of-concept that a tattoo device can target intra-dermal drug delivery against cutaneous leishmaniasis (CL). The selected drug is oleylphosphocholine (OlPC) formulated as liposomes, particles known to be prone to macrophage ingestion. We first show that treatment of cultured Leishmania-infected macrophages with OlPC-liposomes results in a direct dose-dependent killing of intracellular parasites.

First study on efficacy and tolerability of a new alkylphosphocholine molecule (oleylphosphocholine-OlPC) in the treatment of canine leishmaniosis due to Leishmania infantum.

The alkylphosphocholine oleylphosphocholine (OlPC) represents a potential new therapy for the treatment of canine leishmaniosis caused by Leishmania infantum. The aim of the present study was to evaluate the efficacy and safety of OlPC in a small cohort of dogs naturally infected with L. infantum and defined as clinically sick (LeishVet stages II and III).

New development for aorto bifemoral bypass--a clampless and sutureless endovascular and laparoscopic technique.

The classic procedure for aortobifemoral bypass is open surgery. Laparoscopy has been accepted by several authors as a minimal invasive alternative for aortoiliac occlusive disease. The totally retroperitoneal laparoscopic procedure has been described as an alternative to the transperitoneal approach.

Ruptured aneurysm of the popliteal artery. Is the diagnosis still difficult?

The aneurysm of the popliteal artery is the most commonly treated non-aortoiliac aneurysm, accounting for more than 70% of all peripheral aneurysms. The rupture of a popliteal aneurysm is rare and it is often misdiagnosed. In the case of a 46-year old female patient here reported, the patient was referred to our department with the diagnosis of ruptured aneurysm of the right popliteal artery with formation of a large pseudo-aneurysm.

The CD20 homolog Ms4a8a integrates pro- and anti-inflammatory signals in novel M2-like macrophages and is expressed in parasite infection.

Recently, we identified the CD20 homolog Ms4a8a as a novel molecule expressed by tumor-associated macrophages that directly enhances tumor growth. Here, we analyzed Ms4a8a(+) macrophages in M2-associated infectious pathologies. In late-stage Trypanosoma congolense and Taenia crassiceps infections, Ms4a8a expression was detected in hepatic and peritoneal macrophages respectively.

Final results and pharmacoeconomic analysis of a trial comparing two neoadjuvant chemotherapy (CT) regimens followed by surgery in patients with resectable non-small cell lung cancer (NSCLC): a phase II randomised study by the European Lung Cancer Working Party.

Induction cisplatin-based CT improves survival in resectable non-small cell lung cancer (NSCLC). We aimed to determine the respective activity of third-generation (gemcitabine-vinorelbine-cisplatin [GVP]) in comparison with second-generation drugs CT (mitomycine-ifosfamide-cisplatin [MIP]) and their cost-effectiveness as neoadjuvant CT before surgery in NSCLC. Patients with histologically proven initially untreated resectable stages I-III NSCLC were randomised between three courses of MIP or GVP followed by surgery.

IL-10 limits production of pathogenic TNF by M1 myeloid cells through induction of nuclear NF-κB p50 member in Trypanosoma congolense infection-resistant C57BL/6 mice.

A balance between parasite elimination and control of infection-associated pathogenicity is crucial for resistance to African trypanosomiasis. By producing TNF and NO, CD11b(+) myeloid cells with a classical activation status (M1) contribute to parasitemia control in experimental Trypanosoma congolense infection in resistant C57BL/6 mice. However, in these mice, IL-10 is required to regulate M1-associated inflammation, avoiding tissue/liver damage and ensuring prolonged survival.

Tip-DC development during parasitic infection is regulated by IL-10 and requires CCL2/CCR2, IFN-gamma and MyD88 signaling.

The development of classically activated monocytic cells (M1) is a prerequisite for effective elimination of parasites, including African trypanosomes. However, persistent activation of M1 that produce pathogenic molecules such as TNF and NO contributes to the development of trypanosome infection-associated tissue injury including liver cell necrosis in experimental mouse models. Aiming to identify mechanisms involved in regulation of M1 activity, we have recently documented that during Trypanosoma brucei infection, CD11b(+)Ly6C(+)CD11c(+) TNF and iNOS producing DCs (Tip-DCs) represent the major pathogenic M1 liver subpopulation.

The central role of macrophages in trypanosomiasis-associated anemia: rationale for therapeutical approaches.

Bovine African trypanosomiasis causes severe economical problems on the African continent and one of the most prominent immunopathological parameters associated with this parasitic infection is anemia. In this report we review the current knowledge of the mechanisms underlying trypanosomiasis-associated anemia. In first instance, the central role of macrophages and particularly their activation state in determining the outcome of the disease (i.

Understanding the role of monocytic cells in liver inflammation using parasite infection as a model.

Uncontrolled inflammation is a major cause of pathogenicity during chronic parasite infections. Novel therapies should therefore aim at re-establishing the balance between pro- and anti-inflammatory signals during disease to avoid tissue damage and ensure survival of the host. In this context, we are intending to identify strategies capable of inducing counter-inflammatory activity in injured liver and thereby increasing the resistance of the host to African trypanosomiasis as a model for parasite infection.

IL-10 dampens TNF/inducible nitric oxide synthase-producing dendritic cell-mediated pathogenicity during parasitic infection.

Antiparasite responses are associated with the recruitment of monocytes that differentiate to macrophages and dendritic cells at the site of infection. Although classically activated monocytic cells are assumed to be the major source of TNF and NO during Trypanosoma brucei brucei infection, their cellular origin remains unclear. In this study, we show that bone marrow-derived monocytes accumulate and differentiate to TNF/inducible NO synthase-producing dendritic cells (TIP-DCs) in the spleen, liver, and lymph nodes of T.

Experimental expansion of the regulatory T cell population increases resistance to African trypanosomiasis.

Inflammatory responses mounted to eliminate parasites can be lethal if not counterbalanced by regulatory responses protecting the host from collateral tissue damage. Here, we show that the maintained inflammation associated with tissue damage, anemia, and reduced survival of Trypanosoma brucei-infected mice correlates with the absence of the expansion of the regulatory T (T(reg)) cell population. Induction of T(reg) cell expansion via CD28 superagonist antibody treatment in these mice down-regulated interferon-gamma production by T cells and tumor necrosis factor-alpha and reactive oxygen species production by classically activated macrophages, triggered the development of alternatively activated macrophages, delayed the onset of liver injury, diminished the anemia burden, and prolonged the survival of infected animals.

Totally retroperitoneal laparoscopic aortobifemoral bypass.

The classic procedure for aortobifemoral bypass is open surgery. Since the first totally laparoscopic aortobifemoral bypass reported in 1997 by Yves-Marie Dion, laparoscopy has been accepted by several authors as a possible minimally invasive alternative for aorto-iliac occlusive disease. The transperitoneal left retrocolic and retrorenal ways are generally used.

[Endobronchial ultrasound and PET positive mediastinal lymph nodes].

Introduction: In bronchial carcinoma when positron emission tomography with 18-fluorodeoxyglucose (FDG-PET) shows increased emission in the mediastinal lymph nodes, confirmation by tissue biopsy is necessary. In this particular situation we have evaluated the use of real time lymph node aspiration under endobronchial ultrasound control.

Methods: Consecutive patients referred for staging and/or diagnosis of PET positive mediastinal nodes in the setting of suspected or confirmed bronchial carcinoma were included.

Multimedia article. Entirely thoracoscopic pneumonectomy using the prone position: a new technique.

Background: Reports on video-assisted pneumonectomy have remained scarce, despite early demonstration of its technical feasibility. A totally videothoracoscopic pneumonectomy was first reported by Conlan and Sandor. The patient in this report was positioned in the full lateral position.

[EGF-R expression correlation between biopsy and surgical specimens of lung carcinoma].

Introduction: Most of the time, biological parameters are evaluated on tissues obtained on surgical samples of the primary tumour. New approaches in non small cell lung cancer (NSCLC) treatment consist to administer neoadjuvant chemotherapy or anti-EGF-R (epidermal growth factor receptor) drug.

Methods: We assessed the expression of EGF-R by immunohistochemistry on biopsy samples and on the paired resected tumours in 27 patients.

Expression of thrombospondin in non-small cell lung cancer.

Objective: Initially considered as an inhibitor of angiogenesis, the role of thrombospondin is currently controversial. The primary purpose of our study was to determine the expression of thrombospondin (TSP) in invasive lung tumours. The secondary objectives were to investigate its relationship with other factors related to angiogenesis and to assess their clinicopathological significance.

Synchronous roentgenographically occult lung carcinoma in patients with resectable primary lung cancer.

Objective: To assess the prevalence of synchronous roentgenographically occult lung carcinoma (ROLC) in patients with resectable roentgenographically visible lung cancer (RVLC).

Methods: Patients undergoing surgery for RVLC in the same University Hospital were prospectively evaluated before surgery by fluorescence bronchoscopy under local anesthesia to detect synchronous ROLC. All abnormal areas, with the exception of the RVLC, had biopsies made.

Carbonic anhydrase IX antigen differentiates between preneoplastic malignant lesions in non-small cell lung carcinoma.

The MaTu interval (MN)/carbonic anhydrase (CA) IX tumour-associated antigen is a protein that is normally expressed in the gut and belongs to the carbonic anhydrase enzyme family (CA IX). It has been detected in tumour cell lines and in some solid tumours including cervical, oesophageal and clear cell renal carcinoma. This study determined MN/CA IX expression in 65 primary non-small cell lung cancer resected with curative intent and in 38 bronchial preneoplastic lesions, carcinoma in situ or microinvasive carcinoma as well as in normal bronchial tissue.

Detection of bronchial preneoplastic lesions and early lung cancer with fluorescence bronchoscopy: a study about its ambulatory feasibility under local anaesthesis.

Background: Autofluorescence bronchoscopy (AB) enhances the bronchoscopist's ability to diagnose bronchial preneoplastic lesions and early cancer. We undertook a study to assess its feasibility and performance under local anaesthesia on a real ambulatory mode.

Methods: Thirty-four consecutive patients at very high risk for lung cancer were prospectively studied by AB under local anaesthesia, without any sedation.