Secretion of a chemotactic factor for neutrophils and eosinophils by alveolar macrophages from asthmatic patients

The studies presented in this article demonstrate the release of an IgE-dependent chemotactic factor for polymorphonuclear neutrophils (PMN) and eosinophils by alveolar macrophages (AMs) from normal subjects (n = 15) and allergic asthmatic patients (n = 15). A 60-minute incubation of normal AMs previously sensitized by 20% nonheated allergic sera with anti-human IgE antibody or the related allergen induced the release of a chemotactic activity (CA) for PMN and eosinophils in culture supernatants. When AMs were obtained from asthmatic patients, direct incubation with anti-IgE or the related allergen induced the same CA, whereas incubation with an unrelated allergen failed to produce CA (neutrophil CA after addition of anti-IgE, 22.5 +/- 3.5 cells per high power field; with related allergen, 15.8 +/- 3.6; with unrelated allergen, 0.7 +/- 1.8; p less than 0.0001). A partial characterization of the neutrophil chemotactic factor was carried out. Enzymatic treatment by trypsin or carboxypeptidase or by heating (56 degrees C for 3 hr) failed to abolish the neutrophil CA. After gel filtration the greater part of the neutrophil CA (80%) was recovered among low-molecular-weight components (300 to 1300 daltons). A preliminary deactivation of PMN by leukotriene B4 suppressed the CA of AM supernatants. These results indicate that IgE-dependent stimulation of AMs produces a neutrophil and eosinophil CA, present in a low-molecular-weight fraction possibly related to leukotrienes, and emphasizes the role of AMs in inflammatory lung processes during allergic asthma.     

Endotoxin-induced desensitization of mouse macrophages is mediated in part by nitric oxide production.

Refractoriness (tolerance) to endotoxin effects, such as induction of tumor necrosis factor alpha (TNF-alpha) secretion, can be elicited in vitro in macrophages by preexposure of cells to endotoxin (lipopolysaccharide [LPS]) itself. The aim of this study was to determine whether this phenomenon is due to negative feedback mediated by the free radical nitric oxide (NO) produced by cells when they are activated by LPS. Among several efficient inhibitors of NO production, NG-monomethyl-L-arginine did not induce concomitant inhibition of TNF-alpha secretion. Mouse macrophages that were exposed to LPS in the presence of NG-monomethyl-L-arginine partially maintained the ability to secrete TNF-alpha in response to a second LPS stimulation, compared with cells preexposed to LPS alone, thus suggesting that NO is involved in part in LPS-induced desensitization of cells. Furthermore, direct exposure of cells to the NO-generating compounds sodium nitroprusside and S-nitroso-N-acetylpenicillamine mimicked LPS-induced desensitization. However, low concentrations of a synthetic lipid (lipid M4) that is structurally analogous to the reducing end of the lipid A moiety of LPS induced desensitization of mouse macrophages without concomitant production of NO. Taken together, these data suggest that although NO actually takes part in LPS-induced desensitization of mouse macrophages, additional and yet unknown mechanisms must also exist.     

Place des gamma-caméras portables en cancérologie mammaire

Non-palpable breast cancers are more and more frequent. Their surgical management requires the excision of the tumor and sentinel lymph node (SLN) needing a technical preoperative organization combining preoperative identification of the tumor by wire guide and injection of a radioactive tracer for the identification of SLN. The implementation of this minimally invasive surgery is sometimes paradoxically complicated due to the presurgical organization requiring several medical teams. It is for this reason that hand-held gamma-cameras have been developed, used either preoperatively or during surgery to replace lymphoscintigraphy but also as a help to excision of the tumor after radioisotope injection. The objective of this study was to evaluate the interest of the main hand-held gamma-cameras used in breast cancer.     

Narrative medicine as a means of training medical students toward residency competencies

Objective

This study sought to explore the perceived influence of narrative medicine training on clinical skill development of fourth-year medical students, focusing on competencies mandated by ACGME and the RCPSC in areas of communication, collaboration, and professionalism.

Methods

Using grounded-theory, three methods of data collection were used to query twelve medical students participating in a one-month narrative medicine elective regarding the process of training and the influence on clinical skills. Iterative thematic analysis and data triangulation occurred.

Results

Response rate was 91% (survey), 50% (focus group) and 25% (follow-up). Five major findings emerged. Students perceive that they: develop and improve specific communication skills; enhance their capacity to collaborate, empathize, and be patient-centered; develop personally and professionally through reflection. They report that the pedagogical approach used in narrative training is critical to its dividends but misunderstood and perceived as counter-culture.

Conclusion/Practice implications

Participating medical students reported that they perceived narrative medicine to be an important, effective, but counter-culture means of enhancing communication, collaboration, and professional development. The authors contend that these skills are integral to medical practice, consistent with core competencies mandated by the ACGME/RCPSC, and difficult to teach. Future research must explore sequelae of training on actual clinical performance.     

A hand-held imaging probe for radio-guided surgery: physical performance and preliminary clinical experience

Improvements in the specificity of radiopharmaceutical compounds have been paralleled by an upsurge of interest in developing small detectors to assist surgeons in localizing tumour tissue during surgery. This study reports the main technical features and physical characteristics of a new hand-held gamma camera dedicated to accurate and real-time intra-operative imaging. First clinical experience is also reported. The POCI (Per-operative Compact Imager) camera consists of a head module composed of a high-resolution interchangeable lead collimator and a CsI(Na) crystal plate optically coupled to an intensified position-sensitive diode. The current prototype has a 40-mm diameter field of view, an outer diameter of 9.5 cm, a length of 9 cm and a weight of 1.2 kg. Overall detector imaging characteristics were evaluated by technetium-99m phantom measurements. Three patients with breast cancer previously scheduled to undergo sentinel lymph node detection were selected for the preliminary clinical experience. Preoperative images of the lymphatic basin obtained using the POCI camera were compared with conventional transcutaneous explorations using a non-imaging gamma probe. The full-width at half-maximum (FWHM) spatial resolution was investigated in both air and scattering medium; when the phantom was placed in contact with the collimator, the POCI camera exhibited a 3.2 mm FWHM. The corresponding sensitivity was 290 cps/MBq. The preliminary clinical results showed that POCI was able to predict the number and location of all SLNs. In one case, two deep radioactive nodes missed by the gamma probe were detected on the intra-operative images. This very initial experience demonstrates that the physical performance of the POCI camera is adequate for radio-guided surgery. These results are sufficiently encouraging to prompt further evaluation studies designed to determine the specific and optimal clinical role of intra-operative imaging devices.     

Rearrangements of the Pim-1, c-myc, and p53 genes in Friend helper virus-induced mouse erythroleukemias

The Friend helper leukemia virus (F-MuLV) induces in mice leukemias of the erythroid, lymphoid, and myeloblastic lineages. Erythroleukemic cell DNAs were examined for genetic alterations at loci described as common proviral integration regions in MuLV-induced myeloid or lymphoid leukemias or in Friend complex-induced erythroleukemias. No alteration of the Fim-1, Fim-2, Fim-3, pvt-1, and Spi-1 loci were detected in 17 erythroleukemias, p53 gene rearrangement was observed in 6 (30%) erythroleukemias and was always associated with a loss of the germ line allele. Interestingly, genetic alterations were also detected at two loci, c-myc and Pim-1, previously described as common provirus integration regions in T lymphoid leukemias. Rearrangements of these two genes were often associated with p53 gene alteration within the same tumor.