Micafungin as antifungal prophylaxis in non-transplanted haemotological patients / Micafungina como profilaxis antifúngica en pacientes hematológicos no trasplantados

INTRODUCTION: Fungal infections are a major cause of morbidity and mortality in the haematological patients. These infections are mainly due to Candida spp. and Aspergillus spp. Mortality by these infections is high, but rates have descended in the latest series due to better antifungal agents. Echinocandins are, in vitro, very active against Candida and Aspergillus spp. The objective of the study is to analyse the efficacy and safety of micafungin in the antifungal prophylaxis of haematological patients on chemotherapy. MATERIAL AND METHODS: A multicentre, observational retrospective study was performed in 7 Haematology Departments in Spain. Patients admitted to these departments with chemotherapy or immunosuppressive treatment, and who had received antifungal prophylaxis with micafungin between 1 January 2009 and 31 December 2014 were included. RESULTS: There were 5 cases of probable or proven fungal infection (4.8%) according to the 2008 EORTC criteria: 2 proven, 3 probable. The types of fungal infection were 3 aspergillosis and 2 candidiasis. There were no drop-outs from the prophylaxis with micafungin due to toxicity. CONCLUSION: Micafungin is an antifungal agent which, used in prophylaxis, has demonstrated good efficacy and an excellent toxicity profile, making it an apparently interesting option in patients requiring antifungal prophylaxis during their hospitalisation episode

INTRODUCCIÓN: Las infecciones fúngicas son una importante causa de morbilidad y mortalidad en los pacientes hematológicos. Estas infecciones son principalmente debidas a Candida spp.y Aspergillus spp. La mortalidad debida a estas infecciones es alta, pero ha descendido a lo largo de las últimas series gracias a los mejores agentes antifúngicos. Las equinocandinas son, in vitro, muy activas contra Candida y Aspergillus spp. El objetivo de este estudio es analizar la eficacia y seguridad de micafungina en la profilaxis antifúngica de pacientes hematológicos en tratamiento quimioterápico. MATERIAL Y MÉTODOS: Un estudio multicéntrico, observacional, retrospectivo se llevó a cabo en 7 servicios de Hematología en España. Se incluyeron los pacientes ingresados con quimioterapia o tratamiento inmunosupresor que hubieran recibido micafungina como profilaxis entre el 1 de enero de 2009 y el 31 de diciembre de 2014. RESULTADOS: Hubo 5 casos de infección fúngica probable o probada (4,8%) según los criterios de la EORTC de 2008: 2 probadas, 3 probables. Las infecciones fúngicas fueron 3 aspergilosis y 2 candidiasis. No hubo ningún abandono de la profilaxis con micafungina debido a toxicidad. CONCLUSIÓN: Micafungina es un agente antifúngico que, usado en profilaxis, ha demostrado buena eficacia y excelente perfil de toxicidad, siendo una opción interesante en pacientes que requieren profilaxis antifúngica durante su hospitalización

Micafungin as antifungal prophylaxis in non-transplanted haemotological patients.

OBJECTIVE: Fungal infections are a major cause of morbidity and mortality in the haematological patients. These infections are mainly due to Candida spp. and Aspergillus spp. Mortality by these infections is high, but rates have descended in the latest series due to better antifungal agents. Echinocan-dins are, in vitro, very active against Candida and Aspergillus spp. The objective of the study is to analyse the efficacy and safety of micafungin in the antifungal prophylaxis of haema-tological patients on chemotherapy. METHODS: A multicentre, observational retrospective study was performed in 7 Haematology Depart-ments in Spain. Patients admitted to these departments with chemotherapy or immunosuppressive treatment, and who had received antifungal prophylaxis with micafungin between 1 January 2009 and 31 December 2014 were included. RESULTS: There were 5 cases of probable or proven fun-gal infection (4.8%) according to the 2008 EORTC criteria: 2 proven, 3 probable. The types of fungal infection were 3 as-pergillosis and 2 candidiasis. There were no drop-outs from the prophylaxis with micafungin due to toxicity. CONCLUSIONS: Micafungin is an antifungal agent which, used in prophylaxis, has demonstrated good efficacy and an excellent toxicity profile, making it an apparently interesting option in patients requiring antifungal prophylaxis during their hospitalisation episode.

Infective capacity of Cryptococcus neoformans and Cryptococcus gattii in a human astrocytoma cell line.

Pathogenesis of cryptococcosis in the central nervous system (CNS) is a topic of ongoing research, including the mechanisms by which this fungus invades and infects the brain. Astrocytes, the most common CNS cells, play a fundamental role in the local immune response. Astrocytes might participate in cryptococcosis either as a host or by responding to fungal antigens. To determine the infectivity of Cryptococcus neoformans var. grubii and Cryptococcus gattii in a human astrocytoma cell line and the induction of major histocompatibility complex (MHC) molecules. A glioblastoma cell line was infected with C. neoformans var. grubii and C. gattii blastoconidia labelled with FUN-1 fluorescent stain. The percentage of infection and expression of HLA class I and II molecules were determined by flow cytometry. The interactions between the fungi and cells were observed by fluorescence microscopy. There was no difference between C. neoformans var. grubii and C. gattii in the percentage infection, but C. neoformans var. grubii induced higher expression of HLA class II than C. gattii. More blastoconidia were recovered from C. neoformans-infected cells than from C. gattii infected cells. Cryptococcus neoformans var. grubii may have different virulence mechanisms that allow its survival in human glia-derived cells.

Características biométricas de los meniscos en rodillas de individuos Chilenos / Biometric characteristics of knee meniscus in Chilean individuals

Los meniscos son láminas cartilaginosas que contribuyen a ampliar la escasa concavidad de las superficies articulares de la tibia para recibir a los convexos cóndilos femorales. Satisfacen una necesidad funcional, lo que queda demostrado con su reconstitución después de su extirpación total. Con el propósito de aportar datos sobre sus características biométricas, se registraron diámetros anteroposteriores, transversal y de espesor a diversos niveles, para complementar la anatomía de los mismos en nuestra población. Para ello, se realizó un estudio en 20 meniscos, 10 laterales y 10 mediales, extraídos de cadáveres formolizados, de individuos adultos, chilenos, en los Laboratorios de Anatomía de la Universidad de La Frontera, los cuales se prepararon para efectuar las diversas mediciones, efectuando una limpieza de las estructuras fibrosas que están asociadas a estos cartílagos. Los registros fueron realizados con un caliper digital Mitutoyo de precisión 0,05 mm. El menisco lateral tuvo un promedio para la distancia anteroposterior entre las partes más prominentes del margen anterior del cuerno anterior y el posterior del cuerno posterior de 31,7 mm. La abertura meniscal fue de 11,5 mm; la distancia entre los márgenes anterior y posterior de su cuerno anterior fue de 10,9 mm; la de su cuerno posterior fue de 10,9 mm; el espesor periférico de su parte anterior fue de 3,8 mm, de su parte posterior fue de 6,1 mm y a nivel de su parte media fue de 5,9 mm. El menisco medial tuvo un promedio para la distancia anteroposterior entre las zonas más cercanas a la abertura meniscal de sus extremidades de 43,2 mm. La abertura fue de 26,1 mm; la distancia entre los margenes anterior y posterior de su cuerno anterior fue de 9,2 mm; la de su cuerno posterior fue de 13,5 mm; el espesor periférico a nivel de su parte anterior fue de 4,5 mm, de su parte posterior fue de 6,0 mm y a nivel de su parte media fue de 5,5 mm. Los datos aportados complementarán la anatomía ...

The menisci are cartilage plates that help to expand low concavity of articular surfaces of the tibia to receive the convex femoral condyles. They satisfy functional needs, as has been demonstrated with reconstitution following total excision. In order to provide biometric data on its characteristics, anteroposterior diameters, transverse and thickness at various levels were recorded to complement anatomy of the same in our population. We conducted a study in 20 menisci, 10 lateral and 10 medial from adult Chilean cadaver specimens, in the Anatomy Laboratory, Universidad de La Frontera. The samples were prepared to carry out various measurements cleaning the fibrous structures associated with these menisci. Recordings were registered with a Mitutoyo digital caliper with a 0.05 mm accuracy. Lateral meniscus showed an average anteroposterior distance between horns of 31.7 mm, meniscal opening was 11.5 mm, distance between anterior- posterior borders of the anterior horn was 10.9 mm, of the posterior horn 10.9 mm. The peripheral thickness of its anterior part was 3.8 mm, of its posterior part was 6.1 mm and in its middle section 5.9 mm.The medial meniscus had an average anteroposterior distance between anterior an posterior horn of 43.2 mm. Meniscal opening was 26.1 mm, distance between anterior and posterior borders of the anterior horn was 0.2 mm, in its posterior horn 13.5 mm, peripheral thickness in its anterior part was 4.5 mm, its posterior part was 6.0 mm and at the middle section of the meniscus was 5.5 mm. The data provided will complement anatomy of the menisci in Chilean population.

Biopsia hepática percutánea en pacientes ambulatorios: experiencia clínica de 23 casos / Percutaneous liver biopsy in ambulatory patients: clinic experience of 23 cases

La biopsia hepática sigue siendo importante en el diagnóstico de enfermedades del hígado, apareciendo las complicaciones del procedimiento dentro de las primeras horas, siendo necesario 4-6 horas de observación para su realización. Objetivos: Presentar nuestra casuística y protocolo de 23 casos de biopsia hepática percutánea en régimen ambulatorio. Materiales y Métodos: Revisión de fichas clínicas de pacientes a los que se les realizó el procedimiento. Se analizaron variables demográficas, exámenes de laboratorio, razón de indicación de biopsia y complicaciones mayores y menores durante fase hospitalaria y ambulatoria. Resultados: La edad promedio fue de 53,2 años. 69,56 por ciento eran mujeres y 30,4 por ciento hombres. El menor recuento plaquetario fue de 105.000 x mm3. No se observaron complicaciones mayores, y las menores ocurrieron en 91 por ciento en el período de observación y el 61 por ciento de ellas en las primeras dos horas. Conclusiones: Para la realización de biopsia hepática en pacientes ambulatorios, un período de observación hospitalaria de 5 horas parece ser suficiente, dado que en éste se pesquisan la mayoría de las complicaciones de una población bien seleccionada, permitiendo plantear la realización de este procedimiento en forma ambulatoria en nuestro país.

Hepatic biopsy is important in the diagnosis of hepatic diseases. The potential complications may appear in the first hours after the procedure, therefore it is necessary to consider a period of 4-6 hours of observation. Objectives: To present our protocol and 23 cases of percutaneous liver biopsies in ambulatory regime. Materials and Methods: Review of case histories (case report forms) of the patients that were subjected to the procedure. Demographic variables, laboratory tests, reasons for biopsy, and major and minor complications during hospitalization and ambulatory phase. Results: Average age was 53.2 years; of these, 69.56 percent were women and 30.4 percent men. The lowest plaquetary count was 105.000 x mm3. No major complications were observed, and some of them occurred in a 91 percent during the observation period, and 61 percent during the first two hours. Conclusions: A period of clinical observation of 5 hours seems enough for a biopsy in ambulatory patients. It is during this period when the majority of complications are observed in a well-selected population. This supports the idea of performing this procedure in an ambulatory or outpatient basis on our country.

Decrease of muscarinic cholinergic receptors expression in placenta from rats exposed to methyl parathion.

Placental transfer of methyl parathion (MP), an organophosphate pesticide, could involve effects on cholinergic system. To analyze whether placental cholinergic system is altered by prenatal exposure to MP, expression of muscarinic cholinergic receptors (M1 and M2 subtypes; mAChR) was determined in pregnant rats exposed to MP at 0.0, 1.0, 1.5, and 2.0 mg/kg. An immunohistochemical analysis for M1 and M2 mAChR was performed, and the density of the mAChR signal was measured by image analysis. M1 and M2 mAChR were found in the trophoblast present in the labyrinth, with an 18% predominance of M2 over M1 in the non-exposed group. The expression of M1 and M2 mAChR in placentas exposed to MP showed a decrease when compared with the non-exposed group (P < 0.05); a dose-response effect was not detected. These results demonstrate that prenatal exposure to MP causes changes in the placental expression of mAChR M1 and M2, suggesting that related placental cholinergic functions could be affected.

Axon terminals possessing alpha2C-adrenergic receptors densely innervate neurons in the rat lateral spinal nucleus which respond to noxious stimulation.

The lateral spinal nucleus (LSN) in the rat spinal cord contains projection neurons that are densely innervated by peptidergic varicosities which probably originate from spinal interneurons. The alpha2C-adrenoceptor (alpha2C-AR) is present on axon terminals in this nucleus and therefore norepinephrine is likely to modulate input to LSN neurons. We investigated the involvement of LSN neurons in nociceptive transmission and their relationship with axons that possess alpha2C-ARs. Double-labeling immunostaining experiments showed that alpha2C-ARs are present on axon terminals of excitatory and inhibitory interneurons that frequently contain colocalised peptides. Electron microscopy revealed that alpha2C-AR terminals are presynaptic to dendrites and somata of LSN neurons and predominantly form asymmetric synapses. We retrogradely labeled LSN neurons that project to the caudal ventrolateral medulla and combined this with induction of c-Fos expression by peripheral noxious thermal stimulation along with immunolabelling for the alpha2C-AR and the substance P (neurokinin-1) receptor. This enabled us to identify neuronkinin-1 projection neurons in the LSN that express c-Fos and to determine if such cells receive contacts from alpha2C-AR terminals. The results show that some LSN neurons are activated by noxious stimulation and that this input is likely to be modulated by norepinephrine acting on alpha2C-ARs which are present on axon terminals that are presynaptic to LSN neurons.

Neurokinin-1 projection cells in the rat dorsal horn receive synaptic contacts from axons that possess alpha2C-adrenergic receptors.

Thealpha2C subclass of adrenergic receptor (alpha2C-AR) mediates some of the antinociceptive actions of norepinephrine in the spinal cord. Axon terminals, which possess this receptor, are concentrated in the superficial dorsal horn and originate from spinal interneurons. We performed a series of combined tract-tracing and immunocytochemical studies to determine whether alpha2C-AR-immunoreactive axons target projection neurons that possess the neurokinin-1 (NK-1) receptor because such cells are likely to transmit nociceptive information to the brain. Spinomedullary neurons were labeled by stereotaxic injection of the B-subunit of cholera toxin (CTb) into the caudal ventrolateral medulla of three anesthetized adult rats. After 3 d, the animals were anesthetized again and fixed by perfusion. Sections were cut from midlumbar segments and reacted with antibodies to reveal alpha2C-ARs, CTb, and NK-1 receptors. Retrogradely labeled neurons possessing the NK-1 receptor (n = 45) were examined with confocal microscopy to investigate their relationship with alpha2C-AR-immunoreactive axons. Numerous alpha2C-AR axons were apposed to cell bodies and proximal dendrites of cells in lamina I and also to distal dendrites that originate from labeled cell bodies in lamina III/IV. A combined confocal and electron microscopic method confirmed that these appositions were synaptic. Additional experiments showed that virtually all alpha2C-AR terminals in contact with labeled cells are also immunoreactive for the vesicular glutamate transporter 2 and therefore are glutamatergic. These data suggest that norepinephrine can modulate excitatory synaptic transmission from spinal interneurons to projection cells by acting at alpha2C-ARs. This could be one of the mechanisms that underlie the antinociceptive actions of norepinephrine.

Axon terminals possessing the alpha 2c-adrenergic receptor in the rat dorsal horn are predominantly excitatory.

In this study we used confocal microscopy to show that most (83.67%) alpha(2C)-adrenergic receptor (alpha(2C)-AR)-immunoreactive terminals in the superficial dorsal horn contain the vesicular glutamate transporter 2 and hence are glutamatergic. Few (11.33%) terminals contain glutamic acid decarboxylase (a marker for GABAergic axons) and none were associated with the B subunit of cholera toxin (a marker for myelinated primary afferents) or the vesicular glutamate transporter 1. These data indicate that most dorsal horn axons possessing the alpha(2C)-AR are excitatory and add further support to the suggestion that they originate principally from spinal interneurons.

An investigation of neurones that possess the alpha 2C-adrenergic receptor in the rat dorsal horn.

The function of the alpha(2C) subclass of adrenergic receptor in the spinal cord is unclear at present. Immunoreactivity for this receptor is found predominantly on axon terminals of the superficial dorsal horn but limited information is available about the properties and origin of these axons. The aim of this study was to determine which classes of neurone give rise to axons that possess this receptor and to investigate the synaptic organisation of these terminals. A series of double-labelling experiments was performed to investigate the relationship between the alpha(2C) receptor and each one of 14 chemical markers that label various types of axon terminal in the dorsal horn. Tissue was examined with two-colour confocal laser scanning microscopy. Quantitative analysis revealed that alpha(2C)-adrenergic receptors are not present on terminals of unmyelinated or peptidergic primary afferents and descending noradrenergic or serotoninergic axons. They were found on a proportion of terminals belonging to a mixed population of excitatory and inhibitory spinal interneurones, including those that contain neurotensin, somatostatin, enkephalin, GABA and neuropeptide Y. However, a greater proportion of terminals originating from excitatory interneurones were found to possess the receptor. Electron microscopic analysis revealed that alpha(2C)-adrenergic receptor immunoreactivity is predominantly associated with axon terminals that are presynaptic to dendrites but a small proportion of immunoreactive terminals formed axo-axonic synaptic arrangements. These studies indicate that noradrenaline can modulate transmission in the dorsal horn by acting through alpha(2C)-adrenergic receptors on terminals of spinal interneurones.

Myelinated and unmyelinated primary afferent axons form contacts with cholinergic interneurons in the spinal dorsal horn.

Cholinergic interneurons in laminae III/IV of the dorsal horn contain co-localised gamma-aminobutyric acid (GABA) and frequently form axoaxonic synapses with terminals of primary afferents. They are therefore probably last-order interneurons involved in presynaptic inhibition. The purpose of the present investigation was to determine if these cells receive direct input from primary afferents. Relationships between primary afferents and interneurons were investigated in adult rats. Myelinated primary afferents were labelled with the B-subunit of cholera toxin (CTb). Unmyelinated afferents were labelled with IB4 lectin and an antibody to identify calcitonin-gene-related peptide (CGRP). Cholinergic neurons were labelled with an antibody raised against choline acetyltransferase and examined with a confocal microscope. Cells were reconstructed with NeuroLucida for Confocal and afferent contacts plotted. Interneurons (N=30) received an average of 20.2+/-11.9 (SD) contacts from CTb-labelled primary afferents, which were preferentially distributed on proximal and intermediate dendrites. Interneurons with dendrites which extended into lamina II (N=20) received an average of 27.4+/-19.0 IB4 contacts (on intermediate and distal dendrites) and 9.2+/-6.8 CGRP contacts. It is concluded that cholinergic interneurons receive contacts from both myelinated and unmyelinated primary afferents and different classes of afferent target particular dendritic domains. Cholinergic interneurons are likely to be components of an inhibitory feedback pathway that is monosynaptically activated by primary afferents.

[Hypercoagulability status previous to total hip and knee arthroplasty: the contribution of rheumatoid arthritis]. / Estado hipercoagulativo previo a la artroplastia total de cadera y rodilla: contribución de la artritis reumatoide.

PURPOSE: Starting from a status hypercoagulability previous to substitutive hip and knee surgery, the aim of this work was to investigate the influence of different osteoarthropatic pictures for which arthroplasty is indicated in the activation of the clotting cascade, rheumatoid arthritis (RA) being one of such pictures. PATIENTS AND METHODS: Of 79 patients suitable for prosthetic surgery of hip (53) and knee (26), the preoperative values of several markers, namely, D dimers (D-D), thrombin-antithrombin (TAT) complex, and F1 + 2 prothrombin fragment (F1 + F2) were assessed by enzymoimmunoasay. The mean age of the patients was 65.5 years, and their sex distribution was 50 women and 29 men. The indications for arthroplasty were as follows: osteoarthrosis (62), aseptic necrosis (11), RA (9), articular gout (2), previous fracture (2), more than one diagnosis overlapped in some cases. The results attained were compared with a control group comprised of 33 subjects (16 women and 17 men) with mean age similar to the patient's group (68.06 years). RESULTS: The D-D values in the patients suitable for hip arthroplasty and the TAT values in patients suitable for both types of surgery were significantly higher than those found in the control group (p = 0.012 and 0.01, respectively). The preoperative TAT levels of the RA patients were significantly higher (p = 0.025) than those found in the patients with the other surgical indications. CONCLUSIONS: Previously to the performance of arthroplasty, the patients show hypercoagulative marker values higher than those of age-matched controls. The significant rising of TAT found in RA patients is concordant with the literature, and this fact makes it advisable to include RA among the pathologic situations associated with hypercoagulability, as this is a common indication for substitutive hip and knee surgery with high risk of venous thromboembolic disease.

Neoplasias quísticas del páncreas / Pancreatic cystic neoplasms

Se presenta 10 casos intervenidos por 2 de los autores en los últimos años. Clínicamente 7 pacientes presentaron síntomas (dolor, distensión abdominal) y en 3 de ellos fue un hallazgo intraoperatorio. En los 7 pacientes sintomáticos el diagnóstico se planteó en base a ultrasonografía y/o TAC. En todos los pacientes se resecó la lesión por: pancreatectomía corporocaudal en 7 casos, pancreatoduodenectomía en 2, y tumorectomía en 1 caso. No hubo mortalidad operatoria. El seguimiento de los pacientes entre 1 y 11 años no muestra recidiva tumoral