Quality of life, coping strategies, social support and self-efficacy in women after acute myocardial infarction: a mixed methods approach.

BACKGROUND: Quality of life, coping strategies, social support and self-efficacy are important psychosocial variables strongly affecting the experience of acute myocardial infarction (AMI) in women. AIMS: To gain a more in-depth understanding of how coping strategies, self-efficacy, quality of life and social support shape women's adjustment to AMI. DESIGN: Mixed methods study. Quantitative data were collected through a standardised questionnaire on coping strategies, self-efficacy, quality of life and social support. Qualitative data stemmed from 57 semistructured interviews conducted with post-AMI female patients on related topics. METHODS: Quantitative data were analysed with unpaired two-sample t-tests on the means, comparing women who experienced AMI (N = 77) with a control group of women who did not have AMI (N = 173), and pairwise correlations on the AMI sample. Qualitative data were grouped into coding families and analysed through thematic content analysis. Qualitative and quantitative results were then integrated, for different age groups. RESULTS: Quantitative results indicated statistically significant differences between women who experienced AMI and the control group: the former showed lower self-perceived health, perceived social support and social support coping, but greater self-efficacy, use of acceptance, avoidance and religious coping. Pairwise correlations showed that avoidance coping strategy was negatively correlated with quality of life, while the opposite was true for problem-oriented coping, perceived social support and self-efficacy. Qualitative results extended and confirmed quantitative results, except for coping strategies: avoidance coping seemed more present than reported in the standardised measures. CONCLUSION: Mixed methods provide understanding of the importance of social support, self-efficacy and less avoidant coping strategies to women's adjustment to AMI. RELEVANCE TO CLINICAL PRACTICE: Women need support from health professionals with knowledge of these topics, to facilitate their adaptation to AMI.

Phase II study of the PI3K inhibitor BKM120 in patients with advanced or recurrent endometrial carcinoma: a stratified type I-type II study from the GINECO group.

Backround:Patients with metastatic endometrial carcinoma have a poor prognosis and PIK3CA mutations and amplifications are common in these cancers. This study evaluated the efficacy and safety of the pure PI3K inhibitor BKM120 in advanced or recurrent endometrial carcinoma. METHODS: This phase II, multicentre, single-arm, double strata (histological low grade (LG) or high grade (HG)) open-label study enrolled patients with histologically confirmed advanced or recurrent endometrial carcinoma who had received not more than one prior chemotherapy regimen. Patients received initially BKM120 100 mg tablets once daily. Primary end points were proportion of patients free of progression at 2 months (HG strata) or at 3 months (LG strata), objective response rate (ORR), and safety. RESULTS: A total of 40 patients were enrolled, of whom 16 patients had received BKM120 at 100 mg. Because of high toxicities (cutaneous rash (54%), depressive events (47%), and anxiety (40%), the IDMC has proposed to stop recruitment at 100 mg and to continue the clinical trial with a lower dose of 60 mg per day. In addition, 24 patients (median age 67 years old) were newly enrolled (14 in the LG strata and 10 in the HG strata). Rate of nonprogression at 2 months in the HG strata was 70% and at 3 months was 60% in the LG strata. Median progression-free survival (PFS) for all patients is 4.5 months (CI 95% 2.8-6.1), and the median PFS for LG strata is 8.3 months compared with 3.8 months for the HG strata. No response was reported. At 60 mg per day, the most commonly reported treatment-related adverse events (AEs) were hyperglycaemia (58%), cognitive (31%), digestive (28%), hepatic liver functions (26%), and rash (23%). The most commonly reported treatment-related grade ⩾3 AEs were HTA (17%), hyperglycaemia (17%), and increased alanine aminotransferase (24%). Five patients (21%) stopped BKM120 for toxicity. CONCLUSIONS: The BKM120 was associated with an unfavourable safety profile and minimal antitumour activity in monotherapy in advanced or recurrent endometrial carcinoma. The clinical trial was stopped before end of recruitment for toxicity.

Thymocytes in Thy-1-/- mice show augmented TCR signaling and impaired differentiation.

Thy-1, a single variable-like immunoglobulin superfamily domain anchored in the plasma membrane by a glycosyl phosphaditylinositol tail [1], is a major surface glycoprotein in adult mammalian neurons and rodent thymocytes [2]; the function of Thy-1 has remained enigmatic since its discovery [3]. Studies in vitro have implicated Thy-1 in homotypic and heterotypic cell-cell interactions [2,4]. Ligation of Thy-1 initiates transmembrane signaling pathways that lead to diverse physiological outcomes in different cells [2,5-7]. In rodents, Thy-1 is highly expressed on the surface of CD4+CD8+ double-positive immature thymocytes and downregulated in mature T cells. Here, we report that thymocytes from Thy-1-/- mice [8] had altered cell-cell contacts, and hyperresponsiveness to T-cell receptor (TCR) triggering as demonstrated by the heightened activation of p56lck, phosphorylation of TCR subunits, Ca2+ fluxes and cell proliferation. Thy-1-/- thymocytes exhibited impaired maturation from the double positive to single positive stage of thymocyte development, possibly due to inappropriate negative selection, and were prone to T lymphomas in aged mice. These observations indicate that Thy-1 negatively regulates TCR-mediated signaling and controls activation thresholds during thymocyte differentiation.

Ultrastructure of spontaneously differentiated human malignant melanocytes cultured from primary tumors.

Ultrastructural study of early subcultures and established lines of human malignant melanocytes derived from primary tumors showed that melanocytes passed through a phase of dedifferentiation during which they took on a fibroblast-like appearance; then they had a phase of spontaneous redifferentiation. The fibroblast-like cells were characterized by the presence of network-like organelles in their cytoplasm, and the melanocytes by melanosomes.

Ultrastructural comparison between cultured and tumor cells of human malignant melanoma.

Tumor cells from 28 human malignant melanomas were compared by electron microscopy with cultured cells of 17 established human melanoma cell lines derived from the same types of tumors. Both tumor and cultured cells were classified into five types according to their different fine-structural characteristics. There was a correlation between the cell types observed in the tumor fragments and in the cell lines. This evidence suggests that cultured human melanoma cells retained in vitro the characteristics of the melanoma cells in vivo, from which they were derived.

Ultrastruct and biochemical chantes in cultured human malignant melanoma cells after heterotransplantation into nude mice.

Cells from three lines of cultured human malignant melanomas were heterotransplanted into nude mice and then recultered. The shape of the cells, the aspect of the melanosomes, and the content of 5-S-cyteinyldopa showed pronounced changes induced by the transplantation. Such results indicate that this experimental model should be used with great caution. A relationship was found between the shape of the melanosomes and the content of 5-S-cysteinyldopa in the cells.

Relationship between phagosome acidification, phagosome-lysosome fusion, and mechanism of particle ingestion.

The fate of pathogens ingested by macrophages is dependent on phagosome acidification and fusion with different intracellular vesicles. Whereas the mode of particle recognition by the phagocyte seems the main determinant of phagosome-lysosome fusion, the influence of membrane reorganization, fusion events, and cell activation in phagosome acidification is not well known. We looked for a relationship between the nature of receptors involved in phagocytosis, phagosome acidification, and phagosome-lysosome fusion. Murine macrophage-like P388D1 cells were made to ingest sheep erythrocytes coated with immunoglobulin G (EIgG) or IgM and complement (EIgMC) or treated with glutaraldehyde and periodate (EGP). The following results were obtained: (1) As expected, the adhesion of the three particle types was differentially inhibited by monoclonal antibodies specific for Fc gamma RII and CD11b/CD18. (2) The phagosomes containing all three particle types displayed similar acidification kinetics with a pH decrease to 6 within the first 10 min after ingestion. (3) Only phagosomes containing EIgG or EIgMC were fused with peroxidase-loaded secondary lysosomes. (4) Coating EGP with IgG only partially restored fusion, even when the surface density of IgG was markedly higher than found on EIgG. It is concluded that phagosome acidification and fusion are regulated by different mechanisms. Also, the lack of fusion observed with EGP is not entirely accounted for by the absence of stimulation of suitable receptors on the phagocyte membrane, because it cannot be restored by providing such a stimulus.

Leukosialin (CD43) behavior during adhesion of human monocytic THP-1 cells to red blood cells.

To understand the modulation and the behavior of glycocalyx elements during adhesion, we explored one of its components, the CD43 molecule, on human monocytic THP-1 cells exposed to cytokine stimulation and its redistribution during heterotypic adhesion to opsonized erythrocytes. First we demonstrated by immunofluorescence and immunoprecipitation that CD43 is dys-sialylated in monocytic THP-1 cells stimulated by interferon-gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) and stimulation increased correlated to heterotypic adhesion. CD43 anti-adhesive effect seemed to be related to sialic acid moeties because an increase in adhesion was also induced by sialidase treatment and by monoclonal antibodies recognizing sialic acid-dependent epitopes on CD43. Second, a redistribution of CD43 molecules was observed after adhesion, resulting in the exclusion of CD43 molecules from contact areas as demonstrated by immunofluorescence and by ultrastructural immunogold localization. We therefore demonstrated in monocytic THP-1 cells that some glycocalyx molecules can be modulated by cytokines and redistributed during adhesion. These results support the concept that CD43 can regulate cell interactions.

[Guillain-Barré syndrome and non-Hodgkin's lymphoma. Report of one case and review of literature]. / Syndrome de Guillain-Barré et lymphome non-hodgkinien. A propos d'une observation et revue de la littérature.

Patients with lymphoma frequently develop neurologic abnormalities mainly due to nervous system infiltration but also direct drug toxicity. Moreover Guillain-Barré syndrome (GBS) remains a possible neuropathy, rarely described in non-Hodgkin's lymphoma. We describe a case of GBS in a patient with non-Hodgkin's high grade lymphoma. A 74-year old man with a newly diagnosed stage I high-grade lymphoma (precursor B-cell Burkitt like type according to the R.E.A.L. Classification) develop flaccid quadriparesis, 7 days after the end of the third course of CHOP treatment. The clinical course and neurological examination were consistent with GBS. The patient was in tumoral complete response. Despite appropriate treatment and a transfer in a reanimation unit, the patient died 3 days after the beginning of neurologic symptoms. The low number of cases described in the international literature doesn't permit to understand the association of this neurologic disease with non-Hodgkin's lymphoma. Collecting more data could lead interesting information to know the place of malignant hematological disease in the natural history of GBS.

Cellular localization of tyrosinase in human malignant melanoma cell lines.

Human malignant melanocytes show characteristic morphologic modifications which are particularly evident in their specific organelles: melanosomes. These modifications are conserved in cell culture. The ultrastructural localization of tyrosinase, the enzyme which converts tyrosine and dopa into melanin, was determined in 13 human melanoma cell lines. The different cell lines possess 4 distribution patterns of melanin synthesis based on dopa oxidase activity. The two first pathways, which involve the Golgi apparatus, seem to differ by the amount of enzyme within this organelle. The third pathway mainly involves the smooth endoplasmic reticulum, whereas tyrosinase is visible only in vesicles in the fourth. Some cells synthesize the enzyme in the manner observed in very early embryos.

Adhesion-related glycocalyx study: quantitative approach with imaging-spectrum in the energy filtering transmission electron microscope (EFTEM).

Large polysaccharide molecules composing the glycocalyx have been shown to prevent cell adhesion. However, this process was not observed microscopically. Terbium labeling, combined with a new quantitative imaging method based on electron energy loss spectroscopy, allowed specific glycocalyx staining with excellent contrast. Image analysis enabled us to compare glycocalyx structure in free membrane areas and contacts between monocytic cells and bound erythrocytes. Apparent glycocalyx thickness, in contact areas, was half of the sum of glycocalyx thicknesses in free areas without label density increase. Ultrastructural immunogold localization of CD43 molecules, a major component of glycocalyx, was also demonstrated to be excluded from contact areas during adhesion. Thus, both approaches strongly suggest that some glycocalyx elements must exit from contact to allow binding of adhesion molecules.

An analysis of potential factors allowing an individual prediction of cisplatin-induced anaemia.

Severe cisplatin (CP)-induced anaemia significantly impairs the patient's quality of life. Prevention based on erythropoietin (EPO) administration would be cost-effective providing that individual predictive factors of anaemia are identified. The aim of the present study was to identify parameters able to predict the occurrence of CP-related anaemia. This prospective study was conducted on 40 head and neck cancer patients receiving a CP (100 mg/m(2), intravenous (i. v.) on day 1) - 5-fluorouracil (5-FU, 1 g/m(2)/dx5 days by continuous infusion) induction chemotherapy. Three cycles were given at 3-weekly intervals. Platinum pharmacokinetics (total and ultrafilterable plasma platinum concentration measured 16 h after CP administration) and 5-FU pharmacokinetics (full-cycle plasma area under the curve, (AUC(0-105h)30 g/l) occurred in 15 patients (38%) and 3 of them also received a blood transfusion. Patient age, 5-FU AUC(0-105h) and total platinum concentration were unrelated to Hb loss. In contrast, ultrafilterable (UF) platinum concentration was significantly correlated to Hb loss: the higher the UF platinum concentration, the greater the Hb loss (P=0.015). A discriminant analysis allowed a cut-off value for UF platinum to be proposed to identify patients developing significant loss of Hb: 91% of patients exhibiting a UF platinum concentration above 50 ng/ml developed significant loss of Hb in contrast to 18% in the group of patients with a UF platinum concentration below 50 ng/ml (odds ratio (95% confidence interval, CI) of 46 (4.7-446)). In conclusion, the present platinum pharmacokinetic survey may be proposed as a valuable approach to identify patients at risk for developing severe anaemia.

Study of cell deformability by a simple method.

Cell deformability plays an important role in many immunological processes, such as phagocyte chemotaxis and endocytosis. The most widely used method of assay consists in aspirating cells into glass micropipettes and measuring the length of the protrusion induced by a given pressure, or the minimum pressure required to drive cells into the micropipette. This procedure requires specialized equipment and delicate manipulation. The present report describes a simpler procedure: cells are centrifuged in petri dishes floating on a water cushion, then fixed and coated with 0.8 micron diameter latex beads, which allows rapid and accurate determination of their height. This method is compared with the micropipette technique by studying lymphocyte and macrophage-like cell lines in physiological medium and in the presence of a divalent cation chelator or a microfilament inhibitor. In addition to simplicity, the main advantages of this technique are that (i) many cells may be examined within a reasonable period of time, which allows testing of heterogeneous cell populations, and (ii) unexpectedly, centrifugation was quite harmless under our experimental conditions, since it did not impair cell proliferative ability nor phagocytic ability. It is concluded that the method may be used in clinical laboratories to explore phagocyte dysfunctions, as well as in experimental studies.

Cell surface fixation of alloantigen bearing plasma vesicles in the presence of polyethylene glycol.

The fixation of plasma vesicles at the surface of intact mouse spleen or tumor cells was studied in order to introduce the foreign alloantigens of the vesicles into the plasma membrane of these cells. A 3-6-fold increase of fixation of radioiodinated vesicles was obtained when cells and vesicles were incubated in the presence of polyethylene glycol 1500 (PEG 1500). The fixation of vesicles on the surface of cells was demonstrated by scanning electron microscopy. Cells treated with vesicles in the presence of PEG acquired the corresponding membrane alloantigens, as demonstrated by cellular binding radioimmunoassay. However, sensitivity to antibody-dependent lysis was obtained only when vesicle fixation was achieved in the presence of both wheat germ agglutinin and polyethylene glycol. The introduction of foreign alloantigens in the plasma membrane of the treated cells might help to define the functional properties of these molecules.

Unexpected cell surface labeling in conjugates between cytotoxic T lymphocytes and target cells.

Specific binding of target cells by cytotoxic T lymphocytes (CTL) is an example of tight interaction between two different cell types. The molecular events that occur at the cell membranes during these interactions are largely unknown. In the present report, we describe an electron microscopic immunostaining study made on CTL-target cell conjugates. Various membrane structures were labeled with monoclonal antibodies specific for structures possibly relevant to cytolysis (Lyt-2, LFA-1, and target cell class I major histocompatibility antigens) or probably unrelated to the cytolytic process (effector cell class I major histocompatibility antigens). Antibodies against Thy-1 were also used. Staining was achieved with immunoperoxidase or immunoferritin. With both techniques nonconjugated cells were either stained or not, depending on whether they bore the antigen corresponding to the antibody used. However, when conjugated to an antigen-bearing cell, a "non-antigen bearing" cell was labeled near the cell interaction area. No increased Fc receptor activity could be detected on bound cells near the interaction area. These data are consistent with the occurrence of limited exchange of membrane macromolecules between bound CTL and target cell.

Localization of calcium changes in stimulated rat mast cells.

We studied intracellular free, bound, and sequestered calcium in rat mast cells after various stimulations. The use of a fluorescent probe combined with digitized imaging on individual living cells demonstrated transient increases of free Ca2+ in the micromolar range. The use of histochemical techniques (K pyroantimonate and anhydrous fixation), together with X-ray microanalysis, energy electron-loss spectroscopy, and electron spectroscopic imaging, revealed large amounts of stored calcium within the cells (in the millimolar range). Chelation experiments and stimulations enabled us to identify at least two pools of bound calcium which exhibited different dynamic behaviors. Stimulation in the presence of EGTA did not modify calcium from granules, granule membranes, and heterochromatin, whereas it decreased calcium from other cell compartments. Stimulation triggered variations in the amount of bound calcium but they did not parallel free calcium movements. Hence, whereas free calcium is implicated in exocytosis, bound calcium may be involved in altogether different cell functions.

Primary lung sarcomas: long survivors obtained with iterative complete surgery.

Primary lung sarcomas are uncommon histologic types of primary lung cancer and presents a wide spectrum of clinical behaviour. Nine patients treated at Antoine Lacassagne Cancer Center between 1982 and 1995 were studied. The median age was 63 years (range, 35-73 years) and the most common histologic types were malignant fibrous histiocytoma (four) and leiomyosarcoma (three). All of them underwent surgery, six patients had a complete surgery and three patients incomplete resections. The median overall survival for all patients was 36 months. In the subgroup of patients with initial complete resection, the median survival was significantly longer (47 months) than in the subgroup of patients with incomplete resection (6 months) (P<0.05, log-rank test). Moreover, two patients had a second complete resection for ipsilateral lung relapse and were long survivors (overall survival of 58 and 83 months, respectively). The ability to achieve a complete second surgery stress the possible benefit of an early detection of local recurrence. Because no specific symptom was linked with the local relapse, a systematic CT scan every 2 or 3 months could be required.

[Correlation between differentiation and malignancy in human malignant melanocytes "in vivo" and "in vitro" (author's transl)]. / Rapport entre différenciation et malignité dans les mélanocytes malins humains "in vivo" et "in vitro".

The relationships between differentiation and malignant transformation were studied in human malignant melanomas in vivo and in vitro. Melanocyte differentiation was assessed by ultrastructural morphological characteristis (the appearance of the melanosomes and related structures) localization of dopa-oxidase and assay of 5-S-cysteinyldopa, a specific metabolite. The transformed characteristic of the cells in vitro was evaluated by their ability to give rise to established cell lines, karyological modifications and heterotransplantation in Nude mice and Syrian hamsters. Morphological variability of the cells in malignant melanomas is accompanied by variability in the localization of dopa-oxidase, the level of 5-S-cysteinyldopa, chromosome pattern and their heterotransplantibility. The lack of pigmentation in some malignant melanoma lines can result from either an irreversible loss of some functions which give rise in melanization and the malignancy in maintained, or by phenomenon of regulation determined by intra or extra-cellular factors with the loss of heterotransplantability. Modulation phenomena affecting tumorigenicity and pigmentation although sometimes concomitant are not identical.

[Cellular differentiation and malignant transformation (author's transl)]. / Différenciation cellulaire et cancérisation.

The mechanisms and determination of differentiation of normal and cancer cells were compared by distinguishing them from the phenomena of regulation, retrodifferentiation and maturation. Reference is made to the laws of order in time and space which are superimposed on the common genetic code during the various types of differentiation. In conclusion, the particular mechanisms of malignant differentiation are discussed by taking melanoma and tumor formation by papova-viruses as examples.

[Image processing and radiotherapy].

Medical images are of great importance in radiotherapy, which became a privileged application field for image processing techniques. Moreover, because of the progression of the computers' performances, these techniques are also in full expansion. Today, the recent developments of the radiotherapy (3DCR, IMRT) offer a huge place to them. Effectively, they can potentially answer to the precision requirements of the modern radiotherapy, and may then contribute to improve the delivered treatments. The purpose of this article is to present the different image processing techniques that are currently used in radiotherapy (including image matching and segmentation) as they are described in the literature.