Update on Actinomucor elegans, a mucormycete infrequently detected in human specimens: how combined microbiological tools contribute efficiently to a more accurate medical care.

Actinomucor elegans is a fungus belonging to mucormycetes and is still probably underdiagnosed due to misidentification. Based on a recent first case of Actinomucor elegans sinusitis in Europe, in an immunocompromised patient under voriconazole treatment, this paper aims to summarize knowledge about A. elegans mucormycoses. Even if the diagnosis of mucormycosis was made using traditional mycology techniques, precise identification of the fungus could only be achieved using molecular tools. In this observation, the galactomannan dosage was positive until the introduction of treatment and surgical debridement. The patient experienced no relapse after one year. By reviewing the four previous A. elegans reported cases and describing the mycological characteristics of this species, we highlight the need to use a combination of tools to improve the diagnostic strategy in such rare and life-threatening clinical situations.

[Hepatic alveolar echinococcosis: a rare cause of recurrent, surgically curable abdominal pain in children]. / L'échinococcose alvéolaire hépatique : une cause exceptionnelle de douleurs abdominales récurrentes, chirurgicalement curable, chez l'enfant.

Hepatic alveolar echinococcosis is a rare parasitic zoonosis, potentially lethal in childhood. It is due to Echinococcosis multilocularis whose larva insidiously develops in the liver. We report the case of a 13-year-old girl, living in the Vosges Mountains, followed for recurrent abdominal pain, with recent worsening. Diagnosis of alveolar echinococcosis was immediately suspected based on the liver ultrasound scan and then confirmed by imaging (CT scan, NMR) and serology. A curative surgical treatment (segmentectomy) was performed 3 months after diagnosis, under oral albendazole treatment, maintained for at least 2 years. Hepatic alveolar echinococcosis usually has a negative prognosis, except if diagnosed early, which allows rapid surgical treatment, as in our patient.

[Initiation and duration of breastfeeding in obstetrical hospitals of Aix-Chambery (France)]. / Initiation et durée de l'allaitement maternel dans les établissements d'Aix et Chambéry (France).

UNLABELLED: Our objectives were to estimate duration of breastfeeding and to identify factors associated with initiation and weaning. METHODS: A prospective study was carried out among 353 mothers delivering in three obstetric hospitals at Aix-Chambery (Savoie, France). Breastfeeding was considered as survival data with censored observations. Univariate and multivariate analyses were performed. RESULTS: Breastfeeding was initiated by 70.8% (66.1-75.5) (exclusive breastfeeding = 39.9% and complementary breastfeeding = 30.9%). Respectively, 58.1% (52.9-63.3) and 12.2% (8.3-16.1) were continuing some breastfeeding at one and six months. The median duration of breastfeeding was 13 weeks (11.6-14.4). Shorter duration was associated with contact beyond one hour from birth (adjusted Hazard Ratio [aHR] = 1.25 [1.03-1.52] and with contact beyond eight hours aHR = 1.78 [1.66-1.92]), pacifier use (aHR = 1.72 [1.19-2.47]), breastfeeding at fixed hours (aHR = 1.78 [1.29-2.45]), and decision to breastfeed during pregnancy or the postpartum period (aHR = 1.70 [1.45-2.00]). CONCLUSION: Breastfeeding initiation and duration were higher in maternity hospitals of Chambéry than estimations measured in the 1998 French perinatal survey and in other ad hoc surveys. Identified factors should be used in order to plan future programs designed to increase duration of breastfeeding.

Endothelial cell activation by myeloblasts: molecular mechanisms of leukostasis and leukemic cell dissemination.

Leukostasis and tissue infiltration by leukemic cells are poorly understood life-threatening complications of acute leukemia. This study has tested the hypothesis that adhesion receptors and cytokines secreted by blast cells play central roles in these reactions. Immunophenotypic studies showed that acute myeloid leukemia (AML) cells (n = 78) of the M0 to M5 subtypes of the French-American-British Cooperative Group expressed various amounts of adhesion receptors, including CD11a, b, c/CD18, CD49d, e, f/CD29, CD54, sCD15, and L-selectin. The presence of functional adhesion receptors was evaluated using a nonstatic adhesion assay. The number of blast cells attached to unactivated endothelium increased by 7 to 31 times after a 6-hour exposure of endothelium to tumor necrosis factor (TNF)-alpha. Inhibition studies showed that multiple adhesion receptors--including L-selectin, E-selectin, VCAM-1, and CD11/CD18--were involved in blast cell adhesion to TNF-alpha-activated endothelium. Leukemic cells were then cocultured at 37 degrees C on unactivated endothelial cell monolayers for time periods up to 24 hours. A time-dependent increase in the number of blasts attached to the endothelium and a concomitant induction of ICAM-1, VCAM-1, and E-selectin were observed. Additional experiments revealed that endothelial cell activation by leukemic myeloblasts was caused by cytokine secretion by blast cells, in particular TNF-alpha and IL-1 beta, and direct contacts between adhesion receptors expressed by blast cells and endothelial cells. Thus, leukemic cells have the ability to generate conditions that promote their own adhesion to vascular endothelium, a property that may have important implications for the pathophysiology of leukostasis and tissue infiltration by leukemic blast cells. (Blood. 2001;97:2121-2129)

Inhibition of selectin-mediated cell adhesion and prevention of acute inflammation by nonanticoagulant sulfated saccharides. Studies with carboxyl-reduced and sulfated heparin and with trestatin a sulfate.

Selectins play a major role in the inflammatory reaction by initiating neutrophil attachment to activated vascular endothelium. Some heparin preparations can interact with L- and P-selectin; however, the determinants required for inhibiting selectin-mediated cell adhesion have not yet been characterized. We now report that carboxyl-reduced and sulfated heparin (prepared by chemical modifications of porcine intestinal mucosal heparin leading to the replacement of carboxylates by O-sulfate groups) and trestatin A sulfate (obtained by sulfation of trestatin A, a non-uronic pseudo-nonasaccharide extracted from Streptomyces dimorphogenes) exhibit strong anti-P-selectin and anti-L-selectin activity while lacking antithrombin-mediated anticoagulant activity. In vitro experiments revealed that both compounds inhibited P-selectin- and L-selectin-mediated cell adhesion under laminar flow conditions. Moreover, carboxyl-reduced and sulfated heparin and trestatin A sulfate were also active in vivo, as assessed by experiments showing 1) that microinfusion of trestatin A sulfate reduced by 96% leukocyte rolling along rat mesenteric postcapillary venules and 2) that both compounds inhibited (by 58-81%) neutrophil migration into thioglycollate-inflamed peritoneum of BALB/c mice. These results indicate that nonanticoagulant sulfated saccharides targeted at P-selectin and L-selectin may have therapeutic potential in inflammatory disorders.

Seasonal variations of interleukin-4 and interferon-gamma release by peripheral blood mononuclear cells from atopic subjects stimulated by polyclonal activators.

IgE synthesis is controlled by interleukin (IL)-4 and interferon (IFN)-gamma, but there is heterogeneity in the IL-4 response depending on the sensitization of patients and natural allergen exposure. In patients sensitized to various allergens, we studied the synthesis of IL-4, IFN-gamma, and IgE to determine to what extent their in vitro immune response may be influenced by pollen season, depending on their sensitization. We studied 12 nonallergic individuals, seven patients sensitized to cypress pollen, 12 sensitized to grass pollen, 14 sensitized to several pollens, and 42 patients with polysensitization. The release of IL-4 and IFN-gamma from peripheral blood mononuclear cells stimulated by polyclonal agents (calcium ionophore A23187 and phorbol myristate acetate) was measured by ELISA. The spontaneous and IL-4-induced release of IgE was measured by ELISA. In patients with cypress pollen allergy, IL-4 and IgE release were significantly lower than in patients with other allergies. In the pollen-sensitized group, IL-4 and IgE release were significantly higher during the pollen season than out of it. No variation in IL-4 or IgE release was observed in the polysensitized group. IFN-gamma production was not affected by the pollen season. These data show that the seasonal variations of IL-4 and IgE synthesis differ according to the sensitization of patients.

Blood monocytes of untreated asthmatics exhibit some features of tissue macrophages.

Airway macrophages are activated in asthmatic subjects. Peripheral blood monocytes from these subjects present some functional features of activation, but their membrane markers are not known. Recently a new subtype of blood monocytes, CD14+/CD16+, has been identified which possesses the characteristics of tissue macrophages. A study was carried out on nine normal subjects and 11 untreated asthmatics having variable severities of the disease to examine the phenotypic characteristics of monocytes. CD14, CD16, HLA-DR, CD11a, CD11b, CD44 and CD54 were studied using double fluorescence flow cytometry since these antigens have been defined in the CD14+/CD16+ monocytes. The functional activation of monocytes was examined using the release of superoxide anion. The co-expression of CD14 and CD16 by monocytes in terms of percentage and mean fluorescence intensity was significantly higher in asthmatics (P < 0.002 and P < 0.0001, respectively, Mann-Whitney U-test). There was no difference for the other membrane markers between asthmatics and normal subjects. Superoxide anion release was significantly increased in asthmatic subjects (P < 0.01). This study shows that most blood monocytes of asthmatics are CD14+/CD16+ and are likely to present features of tissue macrophages.

Release of cytokines by blood monocytes during strenuous exercise.

During strenuous exercise in endurance athletes, monocytes are activated and there is an acute inflammation and hypoxemia possibly due to lesional pulmonary edema. IL-6 and TNF-alpha released by monocytes may be implicated in the acute phase of lesional pulmonary edema. A study was carried out to determine whether TNF-alpha and IL-6 are released during strenuous exercise, and, if adrenalin released during exercise alters their generation. Ten young and six master athletes underwent an incremental exercise test. Arterial blood was drawn at rest, at the end of the exercise, and 20 minutes afterwards. Monocytes were isolated and incubated for 18 hours in the presence or absence of adrenalin. Il-6 and TNF-alpha were measured in monocyte supernatants. The spontaneous release of IL-6 or TNF-alpha was increased in young athletes when compared to older subjects. The spontaneous release of TNF-alpha was increased, but not significantly, by exercise and there was no correlation between the release of IL-6 and TNF-alpha and lung function measured during hypoxemia. Adrenalin inhibited the release of IL-6 or TNF-alpha. Correlations were observed between the in vitro release of IL-6 or TNF-alpha and age, VO2max, maximal ventilation and maximal power output of the subjects.

Modulation of phenotypic and functional properties of normal human mononuclear phagocytes by granulocyte-macrophage colony-stimulating factor.

In asthma, alveolar macrophages (AMs) are hyperreactive releasing large amounts of mediators and expressing high levels of surface markers. Granulocyte-macrophage colony-stimulating factor (GM-CSF) upregulates monocytes and AMs, and may be involved in the hyperreactivity of AMs. The effects of GM-CSF were tested on monocytes and AMs from normal subjects by examining the expression of factors thought to be upregulated in asthma. After various incubation times of GM-CSF, the expression of CD23 and beta 2-integrins (CD11a, CD11b, CD11c) was studied by FACS and the release of sCD23 was measured by ELISA. The priming and stimulatory effects of GM-CSF were tested on monocytes and AMs and the release of leukotriene B4 (LTB4) was measured by ELISA. GM-CSF induced the expression of CD11c and CD23 and the release of sCD23. GM-CSF primed and stimulated monocytes and AMs to release LTB4. The effects of GM-CSF may explain partly the hyperreactivity of AMs in asthma.

Differences in IL-4 release by PBMC are related with heterogeneity of atopy.

Atopy is heterogeneous and the IgE immune response of patients allergic to a single allergen (monosensitized) differs from that of those allergic to multiple allergens (polysensitized). Since interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) regulate human IgE synthesis in vitro, we determined whether cytokines may be involved in the heterogeneity of atopy by comparing the serum IgE and sCD23 titres to the cytokine profile of T lymphocytes from 44 atopic patients (13 mono- and 31 polysensitized) and seven non-atopic subjects. Monosensitized patients were allergic to grass or cypress pollens or house dust mites, and polysensitized ones to many pollen species (n = 5) or many allergens (n = 26). Total serum IgE was lower in the control group than in both atopic groups and in the monosensitized group than in the polysensitized one. IgE immunoblots to orchard grass pollen and house dust mites were less heterogeneous in the monosensitized group than in the polysensitized one. IL-4 production by in vitro-activated peripheral blood mononuclear cells (PBMC) was significantly higher in the polysensitized group than in the monosensitized, and marginal in the control group. In contrast, IFN-gamma production was strongly reduced in both atopic groups, and IL-2 production comparable in the three groups. IgE and soluble CD23 (sCD23) release was higher in the atopic groups than in the control, and higher in the polysensitized group than in the monosensitized one. This study shows that PBMC of mono- and polysensitized subjects have a different IL-4 and sCD23 profile and suggests that human beings may be classified into high and low IgE responders on the basis of IL-4 production.

[Systematic study of sequential salivary gland scintigraphy during rheumatoid arthritis and collagenosis. Apropos of 150 examinations]. / Etude systématique de la scintigraphie salivaire séquentielle au cours de polyarthrites rhumatismales et des collagénoses. A propos de cent cinquante examens

Sequential salivary scintigraphy has been practised systematically in 130 patients hospitalized in a rheumatology unit. These patients were suffering from typical, classical rheumatoid arthritis, rheumatoid arthritis with high positivity for anti-nuclear antibodies, clearly defined polyarthritis, systemic scleroderma, other types of collagenosis, forms of inflammatory polyarticular rheumatism other than rheumatoid arthritis and collagenosis, and from different degenerative diseases. The scintigraphic anomalies were divided in three stages according to a personal classification. Nine patients presented a patend Gougerot-Sjögren syndrome. All of them had abnormal or very abnormal scintigraphy. However, the patients with classical rheumatoid arthritis without signs of the Gougerot-Sjögren syndrome, also showed a high frequency of isotopic anomalies that were equally severe. These were clearly connected only with the particular diagnosis (with classical rheumatoid arthritis, but not with clearly defined polyarthritis or collagenosis). No other direct relationship could be established between these diseases and the clinical, radiological, laboratory, or therapeutic aspects of the case. On the other hand, they were often associated with a reduction in lacrymal and salivary secretion. These isotopic studies, in combination with other findings shed a new light on the Gougerot-Sjögren syndrome, taking into account the diffusion of the exocrine lesions and of the contributions of the most modern methods of investigation.