Osteomyelitis due to Aspergillus spp. in patients with chronic granulomatous disease: comparison of Aspergillus nidulans and Aspergillus fumigatus

AbstractObjective: Chronic granulomatous disease (CGD) is a rare inherited disorder of NADPH oxidase in which phagocytes fail to generate reactive antimicrobial oxidants. Invasive fungal infections are an important cause of morbidity and mortality in CGD patients, with Aspergillus spp. being the most frequent fungal pathogens. We reviewed the reported cases of osteomyelitis in CGD patients due to Aspergillus nidulans and compared them with those due to Aspergillus fumigatus.Methods: Twenty-four cases of osteomyelitis due to Aspergillus spp. in 22 male CGD patients were found in MEDLINE.Results: Fourteen cases (58%) were due to Aspergillus nidulans and ten cases to Aspergillus fumigatus. No other aspergilli were reported as causes of osteomyelitis. Osteomyelitis due to Aspergillus nidulans was associated with pulmonary infection and involved ‘small bones’ more frequently than Aspergillus fumigatus osteomyelitis (p=0.032). Half of the CGD patients with Aspergillus nidulans osteomyelitis died compared with none of those with Aspergillus fumigatus osteomyelitis (p=0.019). In both Aspergillus nidulans and Aspergillus fumigatus cases, cure was achieved by prompt antifungal treatment combined with surgery and immunotherapy.Conclusion: Aspergillus nidulans causes osteomyelitis in CGD patients relatively frequently compared with Aspergillus fumigatus and may be accompanied by higher mortality. This contrasts with the low frequency with which Aspergillus nidulans causes osteomyelitis in patients with other types of immunodeficiency

Central nervous system aspergillosis in children: a systematic review of reported cases

SummaryObjectiveCentral nervous system (CNS) aspergillosis is a life-threatening disease that has had a published mortality of >80%. Little is known about this serious infection in the pediatric population. We conducted this study to analyze characteristics of CNS aspergillosis in infants and children.MethodsThe English literature was reviewed and all CNS aspergillosis cases in patients younger than 18 years of age were analyzed.ResultsNinety cases were recorded up to June 2005. The median age of the patients was 9 years, ranging from 18 days to 18 years (15.6% younger than 1 year). CNS aspergillosis most commonly presented as brain abscess(es), either single or multiple. While prematurity was the predominant underlying condition among infants, leukemia was the most frequent underlying disease in children. Aspergillus fumigatus was isolated from 75.5% of the cases. The overall mortality in published cases was 65.4%. In multivariate analysis, surgical treatment was independently associated with survival.ConclusionCNS aspergillosis in infants and children predominantly presents as brain abscess(es) and has significantly better outcome compared to published adult data. The findings of this systematic review could assist future investigations for improved outcome of this life-threatening infection in pediatric patients

Situación macroeconómica colombiana y reservas internacionales 1990-2005

En el presente documento, se presenta de una forma clara y concisa el comportamiento macroeconómico colombiano para 1990 a 2005, pasando por variables claves de la economía tales como PIB real, Inflación, Tasa de cambio, Cuenta corriente y déficit fiscal , mediante las cuales se observa si Colombia ha experimentado el tener un entorno económico menos previsible que dificulta la acumulación de los diferentes tipos de capital, ya que para que esta se de es necesario que una economía posea niveles de crecimiento económico sostenido para que los diferentes agentes racionales puedan tomar decisiones acertadas en cuanto a inversión y ahorro, de tal manera que mejore la productividad, la inversión extranjera directa y la confianza de los nacionales y extranjeros en dicho país. Para dicho fin se hará un recorrido por el ciclo económico que se dio en la década de los 90`s mirando de 1990-1994 y de 1995-1999, luego, también se analizara el inicio de un nuevo ciclo económico 2000-2005. Además se describe el comportamiento de las reservas internacionales colombianas en los que se hará claro si Colombia ha estado en la mayoría de los últimos quince años en estabilidad o inestabilidad. También es importante resaltar las reservas internacionales, pues son estas el seguro cualquier país frente a posibles choques externos, por eso se mira como esta Colombia en materia del manejo, y acumulación de las reservas, además se hará clara su posición de activos en el exterior a través de un comparativote los principales indicadores de reservas del país frente a los de otros países latinoamericanos como Chile, México, Brasil y Perú. Estos mostraran en parte la vulnerabilidad externa del país además de identificarse o no como apto para préstamos internacionalesTrabajo de grado (Economista)-- Universidad Autónoma de Occidente, 2008PregradoEconomist

Aspergillus species identification in the clinical setting

Multiple recent studies have demonstrated the limited utility of morphological methods used singly for species identification of clinically relevant aspergilli. It is being increasingly recognised that comparative sequence based methods used in conjunction with traditional phenotype based methods can offer better resolution of species within this genus. Recognising the growing role of molecular methods in species recognition, the recently convened international working group meeting entitled “Aspergillus Systematics in the Genomic Era” has proposed several recommendations that will be useful in such endeavors. Specific recommendations of this working group include the use of the ITS regions for inter section level identification and the β-tubulin locus for identification of individual species within the various Aspergillus sections

Emericella quadrilineata as Cause of Invasive Aspergillosis

This opportunistic fungus is frequently misidentified because of its morphologic similarity to E. nidulans

Invasive fungal disease in PICU: epidemiology and risk factors

Candida and Aspergillus spp. are the most common agents responsible for invasive fungal infections in children. They are associated with a high mortality and morbidity rate as well as high health care costs. An important increase in their incidence has been observed during the past two decades. In infants and children, invasive candidiasis is five times more frequent than invasive aspergillosis. Candida sp. represents the third most common agent found in healthcare-associated bloodstream infections in children. Invasive aspergillosis is more often associated with hematological malignancies and solid tumors. Recommendations concerning prophylactic treatment for invasive aspergillosis have been recently published by the Infectious Diseases Society of America. Candida albicans is the main Candida sp. associated with invasive candidiasis in children, even if a strong trend toward the emergence of Candida non-albicans has been observed. The epidemiology and the risk factors for invasive fungal infections are quite different if considering previously healthy children hospitalized in the pediatric intensive care unit, or children with a malignancy or a severe hematological disease (leukemia). In children, the mortality rate for invasive aspergillosis is 2.5 to 3.5 higher than for invasive candidiasis (respectively 70% vs. 20% and 30%)

Complete design of a three-story reinforced concrete warehouse frame for a seismic location

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Human monocytes response to antifungal drugs and to combination of antifungal drugs with interferon-γ in vitro

Purpose: The purpose of this study was to investigate the effects of the 4 amphotericin B formulations [deoxycholate amphotericin B (DAMB) liposomal amphotericin B (LAMB), amphotericin B lipid complex (ABLC), and amphotericin B colloidal dispersion (ABCD)] on the antifungal activity of human monocytes and neutrophils against A. fumigatus and F. solani. In addition, we planned to investigate the effects of caspofungin with or without interferon-γ (IFN-γ) on the monocyte- and neutrophil- induced hyphal damage of A. fumigatus hyphae. Materials-Methods: Human monocytes and neutrophils were obtained from blood of healthy adult volunteers. Antifungal agents used were all four amphotericin B formulations in two different concentrations: DAMB (1 and 5 μg/ml), LAMB, ABLC and ABCD (5 and 25 μg/ml, for each lipid amphotericin B formulation) and the newest echinocandin, caspofungin. Strain of A. fumigatus and F. solani were used in this study. The mRNA levels and protein profiles of cytokines and chemokines expressed by human monocytes were comprehensively evaluated by semiquantitative reverse transcription-PCR and enzyme-linked immunosorbent assays (ELISA). Hyphal damage of A. fumigatus and F. solani was assessed by a modified method of XTT. Antifungal oxidative metabolism was assessed by the following methods: a) superoxide anion production (Ο2⁻) from human monocytes or neutrophils against hyphae of A. fumigatus and F. solani and b) hydrogen peroxide (H₂O₂) and secondary H₂O₂-dependent intracellular intermediates production from human monocytes against hyphae of A. fumigatus. Results: the mRNA levels of TNF-a were increased after incubation with DAMB and ABCD for 2h. ABLC was found to decrease the release of most cytokines and chemokines. DAMB and the rest of lipid amphotericin B formulations did not affect the superoxide anion production. Caspofungin increase hyphal damage induced by pretreated monocytes. Conclusions: deoxycholate amphotericin B and lipid amphotericin B formulations as well as caspofungin have certain immunomodulatory effects on human phagocytes. This means that antifungal agents have another mode of action except of the conventional antifungal action and also explain the role that they can play in the immune response of human body against invasive fungal infections.Σκοπός: Ο σκοπός της μελέτης αυτής ήταν να μελετηθεί η απάντηση των ανθρώπινων μονοκυττάρων και ουδετεροφίλων στη δράση των 4 ειδών αμφοτερικίνης Β [συμβατική δεοξυχολική αμφοτερικίνη Β (DAMB), λιποσωματική αμφοτερικίνη Β (LAMB), αμφοτερικίνη Β σε μορφή λιπιδικών συμπλεγμάτων (ABLC) και αμφοτερικίνη Β σε μορφή λιπιδικού κολλοειδούς (ABCD)] έναντι υφών A. fumigatus και F. solani. Επίσης, μελετήθηκε η επίδραση της κασποφουγκίνης με/ή χωρίς την προσθήκη ιντερφερόνης-γ (IFN-γ) στην καταστροφή των υφών A. fumigatus από μονοκύτταρα ή ουδετερόφιλα. Υλικό-Μέθοδοι. Ως υλικό χρησιμοποιήθηκαν ανθρώπινα μονοκύτταρα και ουδετερόφιλα που απομονώθηκαν από το περιφερικό αίμα φαινομενικά υγιών ενηλίκων αιμοδοτών. Τα αντιμυκητιακά που χρησιμοποιήθηκαν ήταν τα 4 είδη αμφοτερικίνης Β σε δύο διαφορετικές συγκεντρώσεις: DAMB (1 και 5 μg/ml), LAMB, ABLC και ABCD (5 και 25 μg/ml, αντίστοιχα για τα λιπιδικά είδη), καθώς και ένα νεότερο αντιμυκητιακό φάρμακο της κατηγορίας των εχονοκανδινών, η κασποφουγκίνη. Τα στελέχη των μηκήτων που μελετήθηκαν ήταν ο A. fumigatus και το F. solani. Ο προσδιορισμός του αγγελιοφόρου RNA των μονοκυττάρων έγινε με τη μεθοδολογία ανάστροφης μεταγραφής-αλυσιδωτής αντίδρασης πολυμεράσης. Ο προσδιορισμός της παραγωγής κυτταροκινών και χημειοκινών από μονοκύτταρα πραγματοποιήθηκε με την ανοσοενζυματική μέθοδο ELISA. Η καταστροφή των υφών A. fumigatus ή F. solani από μονοκύτταρα ή ουδετερόφιλα προσδιορίστηκε με την χρωματομετρική μέθοδο XTT. Ο αντιμυκητιακός οξειδωτικός μεταβολισμός προσδιορίστηκε: α) με την παραγωγή ανιόντος υπεροξειδίου (Ο2⁻) από μονοκύτταρα ή ουδετερόφιλα έναντι υφών A. fumigatus ή F. Solani, β) με την παραγωγή υπεροξειδίου του υδρογόνου (H₂O₂) και των H₂O₂-εξαρτωμένων ενδοκυττάριων παραπροϊόντων εναλλακτικών μεταβολικών οδών από μονοκύτταρα έναντι υφών A. fumigatus. Αποτελέσματα: Το mRNA του TNF-α αυξήθηκε στα μονοκύτταρα που επωάστηκαν με DAMB και ABCD για 2 ώρες. Η ABLC ελαττώνει την απελευθέρωση των περισσοτέρων κυτταροκινών και χημειοκινών. H DAMB και οι λοιπές λιπιδιακές μορφές αμφοτερικίνης Β δεν επηρέαζαν σημαντικά την παραγωγή υπεροξειδίου ανιόντος. Η κασποφουγκίνη αυξάνει τη μυκητοκτόνο δράση προεπωασμένων μονοκυττάρων. Συμπεράσματα: η δεοξυχολική και τα λιπιδιακά είδη αμφοτερικίνης Β καθώς και η κασποφουγκίνη έχουν ανοσομετατρεπτικές επιδράσεις πάνω στα φαγοκύτταρα. Το γεγονός αυτό έχει ιδιαίτερη σημασία γιατί υποδεικνύει έναν άλλο τρόπο δράσης των φαρμάκων αυτών πλην της αντιμυκητιακής τους δράσης και εξηγεί τη σημασία που μπορούν να έχουν στην άμυνα του οργανισμού, κατά σοβαρών και απειλητικών για τη ζωή συστηματικών μυκητιάσεων