Prospective Evaluation of a New Aspergillus IgG Enzyme Immunoassay Kit for Diagnosis of Chronic and Allergic Pulmonary Aspergillosis.

Anti-Aspergillus IgG antibodies are important biomarkers for the diagnosis of chronic pulmonary aspergillosis (CPA) and allergic bronchopulmonary aspergillosis (ABPA). We compared the performance of a new commercial enzyme immunoassay (EIA) (Bordier Affinity Products) with that of the Bio-Rad and Virion\Serion EIAs. This assay is novel in its association of two recombinant antigens with somatic and metabolic antigens of Aspergillus fumigatus In a prospective multicenter study, 436 serum samples from 147 patients diagnosed with CPA (136 samples/104 patients) or ABPA (94 samples/43 patients) and from 205 controls (206 samples) were tested. We obtained sensitivities of 97%, 91.7%, and 86.1%, and specificities of 90.3%, 91.3%, and 81.5% for the Bordier, Bio-Rad, and Virion\Serion tests, respectively. The Bordier kit was more sensitive than the Bio-Rad kit (P < 0.01), which was itself more sensitive than the Virion\Serion kit (P = 0.04). The Bordier and Bio-Rad kits had similar specificity (P = 0.8), both higher than that of the Virion\Serion kit (P = 0.02). The area under the receiver operating characteristic (ROC) curves confirmed the superiority of the Bordier kit over the Bio-Rad and the Virion\Serion kits (0.977, 0.951, and 0.897, respectively; P < 0.01 for each comparison). In a subset analysis of 279 serum samples tested with the Bordier and Bio-Rad kits and an in-house immunoprecipitin assay (IPD), the Bordier kit had the highest sensitivity (97.7%), but the IPD tended to be more specific (71.2 and 84.7%, respectively; P = 0.10). The use of recombinant, somatic, and metabolic antigens in a single EIA improved the balance of sensitivity and specificity, resulting in an assay highly suitable for use in the diagnosis of chronic and allergic aspergillosis.

Resilience and related factors in urban, mid-aged Spanish women.

OBJECTIVE: To assess resilience and related factors among urban, mid-aged Spanish women. METHODS: This was a cross-sectional study performed in 227 women aged 40-65 years who filled out the 14-item Wagnild and Young Resilience Scale (WYRS-14), the Menopause Rating Scale (MRS) and a questionnaire containing personal sociodemographic data. RESULTS: For the whole sample, median (interquartile range) age and total WYRS-14 score were 52.4 (8.7) years and 79 (20.0) points, respectively. Resilience score was inversely related to non-working status, non-university studies, depressed mood, perimenopausal status, and higher MRS total scores (≥ 17). Using the 25th percentile of the obtained total WYRS-14 score as a cut-off value to define lower resilience (< 68.0 points), logistic regression analysis determined that low resilience was related to being unemployed, having depressed mood and being perimenopausal. Drinking less than 3 units/day of alcohol was significantly related to higher resilience. CONCLUSION: In this sample of urban, mid-aged Spanish women, low resilience (lower WYRS-14 scores) was related to unemployment status, depressed mood and severe menopausal symptoms.

PET-CT and diagnostic CT: the synergy of metabolic and morphological data in onco-haematology.

PURPOSE: Our goal was to determine how interpreting diagnostic CT together with PET-CT could improve the assessment of morphology in onco-haematology. PATIENTS AND METHODS: Fifty-nine patients with aggressive lymphoma were retrospectively included. The diagnostic CT scan was interpreted by two radiologists, followed by a combined analysis of the CT and the PET-CT carried out by two specialists in metabolic and morphological imaging. The diagnostic performances were assessed in terms of sensitivity and specificity, then concordance and discordance rates (kappa) were studied. RESULTS: A combined interpretation of CT and PET-CT showed better diagnostic performances than those of interpretations of CT only in the assessment of nodal sites (826 sites, sensitivity of 99% versus 85%, P<0.05), extranodal sites (649 sites, sensitivity of 88% versus 78%) and bone sites (one analysed per patient, sensitivity of 50% versus 27%). The combined interpretation also improved inter-observer agreement and led to an upgraded Ann Arbor staging in 15% of patients, with a change of treatment in 10%. CONCLUSION: Interpretation of diagnostic CT in onco-haematology can be improved by combining it with an assessment of PET-CT. The synergy between metabolic and morphological information leads to improved diagnostic capabilities and renders interpretations more reproducible.

Hospital-wide prospective mandatory surveillance of invasive aspergillosis in a French teaching hospital (2000-2002).

A multidisciplinary working group devoted to epidemiological surveillance of invasive aspergillosis (IA) was created in January 2000 in Grenoble University Hospital. This article presents the results of a three-year IA surveillance. The multidisciplinary working group surveyed all hospitalized patients, and the mycology laboratory detected most suspected IA cases. Cases were reviewed monthly by the Aspergillosis Committee, and were classified according to international consensus criteria. Possible nosocomial acquisition was determined. Among the 490 alerts, 74 IA cases were observed: six proven cases (8%), 36 (49%) probable cases and 32 (43%) possible cases. The incidence was 4.4 (95% CI 3.4-5.4) IA/100 000 patient-days. Among the proven and probable IA cases, we observed 10 nosocomial cases and six cases of undetermined origin. No cases were noted in the protected rooms in the haematology unit. Only one cluster of cases (three nosocomial cases) was detected in the haematology unit. Forty-three percent of cases (N=32) were hospitalized in the haematology unit, and all other cases were hospitalized elsewhere. This three-year survey found a high rate of non-nosocomial IA cases and a high frequency of IA cases hospitalized in units other than haematology. Thus, this study shows the importance of IA surveillance in haematology units and all high-risk units.

Funiculitis due to Schistosoma haematobium: uncommon diagnosis using parasitologic analysis of semen.

Schistosomal funiculitis is one of the rare localizations of longstanding chronic infection with schistosomiasis. We report a case of a 24-year-old-man who experienced iliac fossa pain and weight loss eight years after his last trip to Mali. Clinical diagnosis of lesions in the genitourinary tract due to schistosomiasis and biologic analysis are required to diagnose this uncommon localization of schistosomiasis.

[Emerging parasitosis ans mycosis: risk and threats for the new millenium]. / Emergence de parasitoses et mycoses: risques et menaces au seuil de troisième millénaire.

For multiple reasons, the emergent infectious risks do not stop increasing these last twenty years. The climatic modifications and the human interventions modifying the biotope as well as the rapid spreading of resistant strains to treatments, generate re-emergence or emergence, all the more dramatic as the means of fight are reduced. These emergent or re-emergent diseases are extremely worrisome as their diagnosis and their prevention are often difficult. The important infesting power of parasites and the particularly effective capacities of adaptation of these eucaryotes contributed to the public health problems. Anthropozoonoses and zoonoses constitute a permanent risk the control of which is imaginary. The new pathogenic agents, the unusual clinical demonstrations in the context of deficiency of the host immune functions imply attentiveness and a permanent up to date of the knowledge of the biologist and of the different professionals of health. The risks with which are confronted the humanity during this century underline the necessity of determining mechanisms involved in the pathogenesis. The determination of the specific and vital biologic processes for the microorganism, could allow to define the most appropriated targets and the most effective and original means of fight.

[Role of local immunity in invasive pulmonary aspergillosis]. / Le rôle de l'immunité locale dans l'aspergillose pulmonaire invasive.

A LEADING CAUSE OF MORTALITY: Inhalation of fungal spores may cause infection and/or inflammation, which is dependent on the nature of the fungus as well as the individual's immune status. Aspergillus fumigatus is responsible for a dramatic pathology, invasive aspergillosis (IA). IA has become a leading cause of death, mainly among bone marrow transplantation or solid-organ recipients, but also among AIDS patients. IMMUNE RESPONSE: The diversity of immune failure suggests that many lines of immunity are implicated in the A. fumigatus elimination process. Non specific immunity plays a major role in the defence against A. fumigatus, including three major lines: anatomical barriers, humoral components, phagocytic cells. But acquired immunity plays a role with different T-cell subsets and their associated cytokines. FUNGUS-HOST RELATIONSHIPS: The relationship between the fungus and its host is complex and could be again study to improve the prevention and the treatment of IA. The aim of this review is a synthesis of the knowledge about the immunity response against Aspergillus fumigatus in IA.

Hydrocortisone, prednisolone and dexamethasone act on Aspergillus fumigatus in vitro susceptibility to itraconazole.

In a previous in vitro investigation from the same laboratory a therapeutic level of hydrocortisone enhanced the itraconazole susceptibility of a single strain of Aspergillus fumigatus. In the present work, the influence of therapeutic levels of hydrocortisone (1 microM), prednisolone (0.125 microM 0.25 microM and 0.5 microM) and dexamethasone (0.25 microM and 0.5 microM) on the itraconazole susceptibility of four A. fumigatus strains, was determined. A. fumigatus conidia were germinated either in the absence or in the presence of a glucocorticoid. The germinated conidia were then spread onto plates and grown either in the presence or in the absence of a glucocorticoid, together with increasing concentrations of itraconazole. The mean colony forming units (CFU) were measured. Two factor analyses of variance showed that hydrocortisone significantly (p <0.001) potentiated the action of itraconazole. The cytotoxic effect of prednisolone on the fungal strains added significantly to the effect of itraconazole (p <0.001). Dexamethasone was also cytotoxic to the fungus but, when used in conjunction with itraconazole, it effectively increased (p <0.01) the number of CFU. This study showed a direct effect of glucocorticoids, currently in use for patient therapy, on in vitro A. fumigatus susceptibility to itraconazole.

[Subcutaneous mycosis due to Scopulariopsis brevicaulis in an immunocompromised patient]. / Mycose sous-cutanée à Scopulariopsis brevicaulis chez un malade immunodéprimé

BACKGROUND: Scopulariopsis brevicaulis is a causal agent of onchomycosis. We report the unusual clinical manifestations caused by this opportunist fungus. CASE REPORT: A 61-year-old man consulted in February 1997 for a budding lesion located on the right medial malleolus. This patient had had a liver transplantation for primary biliary cirrhosis in 1990 and had been taking prednisone and cyclosporine since this time. Cyclosporine had been recently replaced by tacrolimus. The histology examination of a lesion specimen taken from the ankle evidenced a dermal mycosis due to opportunist filamentous fungus. Total excision was performed. The patient then developed nodular lesions of the left elbow during the summer of 1997. Mycology culture of a skin biopsy grew numerous colonies of Scopulariopsis brevicaulis. Excision of the elbow lesion was delayed due to hospitalization for suspected graft rejection and development of insulin-dependent diabetes. The elbow lesion was then resected followed by a skin graft. The mycology examination identified the same causal agent. DISCUSSION: This liver transplant recipient developed two unusual extra-ungual localizations (ankle and elbow) of a Scopulariopsis brevicaulis infection. Chronic immunosuppression favored development of the infection with a pseudo-epithéliomatous presentation. The histology and mycology examinations were necessary for positive diagnosis.

[Benzodiazepine addiction and symptoms of anxiety and depression in elderly subjects]. / Addiction aux benzodiazépines et symptomatologie anxieuse et dépressive chez les sujets âgés.

The relative works to the psychopathological aspects of benzodiazepines (BZD) addiction in elderly persons make the object of a large debate because the question of addiction remains whole. They concern: 1) the influence of age on the level of consumption of the BZD. The research permits to clear 4 explanatory major factors of the relation observed between age and the consumption of BZD: a) the morbidity increased of the aged people, b) the impact of the painful life events, c) the social isolation, d) the weight of the medical prescription; 2) the concepts of dependence (evolution of the definitions, type of physical, psychic or psychopathological dependencies) and of addiction (definitions, place in the international classifications, psychopathological perspective); 3) the reports of the anxiety and the depression with BZD addiction in elderly persons. To the look of these works, the objectives of this present study were to examine the variability of BZD addiction on the one hand within a population weakened by the effects of age (apparition of a chronic illness, for example) and on the other hand the relations that the anxious and depressive symptoms maintain with BZD addiction in elderly persons. Two self-questionnaires were administered: 1) BZD addiction scale, 2) Hospital Anxiety Depression Scale (HAD) to 28 elderly (18 women and 10 men; mean age is 73.25 years). To the exit of this work, the results put in evidence go in the sense of our hypotheses but cannot be generalized to the set of the elderly consumers of BZD, they let appear that age, the depression and the association anxiety/depression predict meaningful manner BZD addiction. Indeed, with regard to age, the polypathology as well as the changes of life induced by the aging process involved BZD addiction in old people. The old age can engender a depression that results in addictive behavior. However, anxiety alone is not experienced before drug addiction in a significant way. This result can explain itself by the fact that the anxiety is a symptom of depression. The present research is unique in several important aspects. First, the study shows that drug addiction in old people cannot be reduced to physiological addiction on product but understood in terms of a complex process requiring an analysis of the psychological addiction on product. Second, BZD addiction in the elderly acts as a psychological/existential medical care. Future research is needed to examine the psychological and psychopathological links that old people maintain with their drug medication.

[Diagnosis of malaria in non-endemic countries : value, limitations and complementarity of existing methods]. / Le diagnostic du paludisme dans les régions non endémiques: valeur, limites et complé mentarité des méthodes actuelles.

The biological diagnosis of malaria is urgent to avoid rapid and fatal outcome. Every year in France, 5,000 imported malaria cases are observed. Thin stained blood smear microscopical examination remains the reference method of diagnosis; however its performance is linked to the professional competence of the biologists. Thus easier methods have been developed (QBC test). Some of them, limited to the diagnosis of malaria due to Plasmodium falciparum do not require highly skilled personal to perform or interpret (antigen detection on dipsticks, tests Parasight or cardboard, ICT Malaria Pf), but limitations and errors occurred. These different tests must be complementary methods of traditional diagnosis. In association with microscopical examinations, they provide rapid and efficient diagnosis of malaria in non-endemic areas. Relying on our experience, the best association is: QBC + thin blood smear and depending of results antigen detection (ParaSight F, ICT Malaria Pf).

Recurrent subcutaneous infection due to Scopulariopsis brevicaulis in a liver transplant recipient.

We describe a case of recurrent Scopulariopsis brevicaulis subcutaneous infection, which occurred 6 years after the patient underwent liver transplantation. Combined surgery and long-term oral therapy with terbinafine resulted in a favorable outcome, although this is not the rule in the previously reported S. brevicaulis infections in immunocompromised patients.

Asymmetric synthesis of 2-methyl cyclohexane carboxylic acids by heterogeneous catalysis: mechanistic aspects

The catalytic hydrogenation of (S)-alkyl-N-(2-methylbenzoyl)pyroglutamates was studied over supported rhodium and ruthenium catalysts at room temperature and a pressure of 5 MPa. The reaction was diastereoselective with the predominant formation of (1S,2R)-2-methylcyclohexane carboxylic acid with a diastereomeric excess (de) of up to 96%. The most stable conformation was determined by means of a combination of modelling calculations, NMR spectroscopy and X-ray structural determination. In this conformation, the carbonyl group of the pyroglutamate auxiliary shields one face of the aromatic ring. The observed selectivity may thus be explained by a preferential adsorption at the unshielded face which avoids steric repulsion by the C=O group to result in a cis hydrogenation. The addition of an amine, the nature of the support (alumina or active carbon) or of the metal (Rh or Ru) were shown to give additional stabilisation of the adsorption at the unshielded face to increase the diastereoisomeric excess.

Identification of amylase crystalloids in cystic lesions of the parotid gland.

OBJECTIVE: To identify alpha-amylase crystalloid formations in parotid specimens obtained by fine needle aspiration. STUDY DESIGN: The study concerned three cases of sialadenitis with crystalloid formation observed between 1993 and 1998. In one of these cases, transmission electron microscopy, mass spectrometry and measurement of amylase activity were used to characterize the nature of the crystalloids. RESULTS: Light microscopy revealed the same crystalloid structure in all three cases. In one case, where the material was saved, a biochemical method made it possible to reveal high amylase activity, while protein electrophoresis and mass spectrometry were used to identify salivary alpha-amylase. CONCLUSION: Crystalloids of salivary alpha-amylase can be identified by May-Grünwald-Giemsa and Papanicolaou stain and can be rapidly confirmed through determination of amylase activity.

Aspergillus Fumigatus antigen detection in sera from patients at risk for invasive aspergillosis.

We have developed an inhibition enzyme immunoassay (inhibition-EIA) to monitor for the occurrence of invasive aspergillosis (IA) in sera from 45 immunocompromised (IC) patients. The test uses rabbit polyclonal antibodies and a mixture of components from Aspergillus fumigatus, containing three predominant antigens with molecular weights of 18,000, 33,000, and 56,000. Circulating antigens were found in five of seven proven cases of IA due to A. fumigatus. In two of the five positive cases, antigenemia was detected with inhibition-EIA earlier than with X ray or other biological methods. No antigens were detected in the sera from two patients with proven IA due to Aspergillus flavus and Aspergillus terreus nor in the sera from four patients with probable IA. Circulating antigens were not detected in the control group, composed of 30 healthy adult blood donors. Four of the 32 at-risk patients examined, though they displayed no definite evidence of IA, gave a positive result in this test. The sensitivity, specificity, and positive predictive value of inhibition-EIA were 71.4, 94.4, and 71.2%, respectively. The data were compared with those obtained by a latex agglutination assay of galactomannan (GM) that was positive in only one patient with probable IA. The higher sensitivity obtained by inhibition-EIA may well be due to its ability to detect circulating antigens other than GM in the sera of IC patients with IA. Detecting these antigens may improve the diagnosis of IA, as they may serve as markers of this infection.

Emerging pathogens.

The ever increasing numbers of immunosuppressed individuals has led to a significant increase in the incidence of opportunistic infections, particularly those caused by fungi. The epidemiology of infections caused by the common fungal pathogens such as Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus has been well documented. However, in addition to these, a number of species which have previously been unrecognized (e.g., C. dubliniensis) or have previously been assumed to be non-pathogenic (e.g., Saccharomyces cerevisiae, Scedosporium spp. and Fusarium spp.) have emerged as agents of human disease. Since these species have only been identified recently as human pathogens, their role in disease is poorly understood. In most cases, identification of these species is problematic and therefore their epidemiology has yet to be elucidated adequately. In addition, several of these species fail to respond to conventional antifungal therapies. In this article, we describe the emergence of two separate yeast species (C. dubliniensis and S. cerevisiae) and two separate groups of moulds (Scedosporium prolificans and Fusarium spp.), as human pathogens. It is apparent from what we already know, that much work has yet to be performed before we have a clear understanding of how these species cause disease and most importantly how they can be controlled.