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Introducción: El papel estimulante de los estrógenos sobre la secreción de prolactina y sobre la proliferación de los lactotropos está bien establecido. Hay escasa literatura sobre los efectos de la menopausia en pacientes con prolactinomas. Objetivos: Evaluar la evolución del tamaño del tumor y de los niveles plasmáticos de prolactina (PRL) en pacientes con microprolactinomas diagnosticados y tratados con agonistas dopaminérgicos (AD) durante su edad fértil y los efectos de la suspensión del tratamiento después de la menopausia. Materiales y métodos: Estudio retrospectivo, multicéntrico. Veintiún pacientes con microprolactinomas diagnosticados durante su edad fértil fueron estudiados en la menopausia. La edad media ± SD de la menopausia fue de 49 ± 3,6 años. En todas las pacientes se suspendió el tratamiento en la menopausia. Resultados: El nivel de PRL pretratamiento fue de 120 ± 58 ng/ml (media±SD) durante la menopausia, al suspender el tratamiento antes de los 12 meses de 23 ± 14 ng/ml y después de 12 meses o más de 1 año de 16 ± 6 ng / ml. Durante la menopausia y al suspender el tratamiento, el tumor desapareció en 9/21 y disminuyó en 12/21 pacientes; un año o más de un año después de la suspensión del tratamiento, el tumor desapareció en 9 /12 y se mantuvo sin cambios en 3/12. La duración promedio del tratamiento fue de 135 ± 74 meses. Dos pacientes reiniciaron el tratamiento debido a que los niveles de PRL aumentaron. Conclusiones: En la mayoría de las pacientes estudiadas se normalizaron los niveles plasmáticos de prolactina y se observó una disminución o desaparición de los microprolactinomas. Los AD podrían suspenderse después de la menopausia en pacientes microprolactinomas. Rev Argent Endocrinol Metab 51:136-141, 2014 Los autores declaran no poseer conflictos de interés.
Introduction: The stimulatory role of estrogens on prolactin secretionn and on proliferation of lactotropic cells is well-established. There is scarce literature about the effects of menopause in patients with prolactinomas. Objectives: To assess the evolution of tumor size and prolactin (PRL) levels in patients with microprolactinomas diagnosed and treated with dopamine agonists bromocriptine (BEC)/cabergoline (CAB) during their fertile age and the effects of discontinuation of those drugs after menopause. Material and methods: retrospective, multicenter study. Twenty-one patients diagnosed with microprolactinomas during their fertile age were studied in their menopause. Mean ± SD age at menopause was 49±3.6 years. In all patients, treatment was stopped when they reached menopause. Results: Mean ± SD pre-treatment PRL level was 120 ± 58 ng/ml and during menopause after stopping treatment, it was 23 ± 14 ng/ml before 12 months, and 16 ± 6 ng/ml after 12 months. During menopause and when stopping treatment, the tumor disappeared in 9/21 and the tumor size decreased in 12/21 patients; a year or more after treatment discontinuation, the tumor disappeared in 9/12 and was unchanged in 3/12. The mean ± SD treatment duration was 135 ± 74 months. Two patients were restarted on treatment because PRL levels increased. Conclusions: Normal PRL levels and sustained reduction or resolution of adenomas were achieved in most patients studied. Only two out of 21 restarted treatment because of hyperprolactinemia. Dopamine agonists might be safely stopped after menopause in patients with microprolactinomas. Rev Argent Endocrinol Metab 51:136-141, 2014 No financial conflicts of interest exist.
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INTRODUCTION: Omalizumab has been demonstrated to be a successful therapy in the management of asthma through reduction of patient's symptoms and use of inhaled corticosteroids. The effect of omalizumab is achieved by immunoglobulin E (IgE) blockage and other secondary mechanisms resulting from this blockage. Because other diseases have an important IgE mediation in their physiopathology, the question arises as to if omalizumab would be useful in the treatment of other IgE-mediated diseases. OBJECTIVE: We present an overview of the experimental studies and clinical reports evaluating the use of omalizumab in diseases different to asthma including atopic dermatitis, urticaria, eosinophilic gastrointestinal disorders, idiopathic anaphylaxis, latex allergy, hymenoptera venom allergy, and other IgE diseases. METHODS: We reviewed the literature using PUBMED, EMBASE, and LILACS for publications which used omalizumab in the treatment of patients with allergic diseases or any other diseases. Complete articles published in English, Spanish or Portuguese were included. CONCLUSION: There is not enough evidence to support the regular use of omalizumab in IgE diseases other than asthma. However, some experimental and clinical investigations indicate that omalizumab could be a therapeutic option in several allergic diseases like atopic dermatitis, urticaria, and eosinophilic gastrointestinal disorders. More control studies are needed in each IgE disease to evaluate the efficacy and safety of omalizumab in IgE mediated diseases.
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Anticuerpos Antiidiotipos/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Asma/tratamiento farmacológico , Hipersensibilidad/tratamiento farmacológico , Inmunoglobulina E/inmunología , Animales , Asma/inmunología , Degranulación de la Célula/efectos de los fármacos , Humanos , Hipersensibilidad/inmunología , Terapia de Inmunosupresión/métodos , Activación de Linfocitos/efectos de los fármacos , Omalizumab , Receptores de IgE/inmunología , Estados Unidos , United States Food and Drug AdministrationRESUMEN
Objetivo: Evaluación del papel de la velocidad sistólica máxima en arteria cerebral media (VSM-ACM) en casos de isoinmunización Rh. Métodos: 67 casos de isoinmunización Rh, en el Hospital La Paz desde febrero del 2006 hasta agosto del 2009, con título de anticuerpos > 1:32, afectación en embarazo previo y/o casos de isoinmunización anti- Kell, en los que se ha realizado medición de la VSM-ACM. Resultados: La capacidad de detección de anemia moderada-severa en base a la medición de VSM-ACM presenta: sensibilidad 80 por ciento (IC95 por ciento: 59,8-100), especificidad y valor predictivo positivo 100 por ciento, y valor predictivo negativo 85,7 por ciento (IC95 por ciento: 70,7-100). El coeficiente de correlación de Pearson entre la hemoglobina estimada y la real es de 0,71. Conclusión: La medición de VSM-ACM predice casos de anemia moderada y severa que son los clínicamente cruciales por la necesidad de actuación obstétrica activa en forma de transfusión intrauterina o finalización del embarazo.
Objective: To evaluate the fetal middle cerebral artery peak systolic velocity (MCA-PSV) in the management of Rh isoimmunized pregnancies. Methods: 67 pregnancies complicated by Rh isoimmunization, in La Paz Hospital ( Madrid) since 2006 February until 2009 August 2009, with maternal antibody titers > 1:32, affected in previous pregnancies and/or anti-Kell isoimmunization, in which MCA-PSV has been measured. Results: For the detection of moderate-severe fetal anemia, Doppler ultrasonography of the middle cerebral artery had a sensitivity of 80 percent (CI95 percent: 59.8-100), a specificity and positive predictive value of 100 percent, and a negative predictive value of 85.7 percent (CI95 percent: 70.7-100). The Pearson correlation coefficient between estimated hemoglobin and real hemoglobin is 0.71. Conclusion: The measurement of MCA-PSV predicts moderate-severe fetal anemia cases, which are the most important in the clinical management because of the need of active treatment with intrauterine transfusion or induction labor.
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Humanos , Femenino , Embarazo , Anemia/diagnóstico , Arteria Cerebral Media/fisiopatología , Isoinmunización Rh/fisiopatología , Velocidad del Flujo Sanguíneo/fisiología , Anemia/terapia , Transfusión de Sangre Intrauterina , Cordocentesis , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Riesgo , Sensibilidad y EspecificidadRESUMEN
AIM: To study the quality of life (QoL) and functional neurological status of patients three years after suffering their first ischaemic cerebrovascular accident (CVA). PATIENTS AND METHODS: For the study we chose patients who presented ischaemic CVA, classified in categories I 63 to I 69. QoL and functional neurological status were measured using the modified Rankin Scale (mRS) and the SF-36 health questionnaire, respectively. RESULTS: Of a total of 59 patients who answered the surveys (mean age: 62 years; sex: 51% females), nearly half of them (29 patients; 49.1%) presented some kind of disability (mRS = 2). Thirty patients (50.9%) were independent or presented minimum sequelae (mRS = 1) at the end of the follow-up period. The mean QoL with the SF-36 questionnaire progressively diminished as the mRS score increased, especially in the group with mRS = 3. Although the youngest age group (range: 20-36 years) got the best average score (84 points) on the SF-36, no significant differences were found with the remaining age groups; the group made up of 75-year-olds and above was the one that obtained the lowest average score (63 points). Extensive strokes (total anterior circulation infarctions) of a cardioembolic origin (atrial fibrillation) had the lowest QoL indexes (p < 0.05). CONCLUSIONS: In the population that was analysed, the QoL was inversely proportional to the age and the severity of the functional deficit of patients who survived a completed stroke, especially in the cardioembolic-origin subgroup, due to its being associated with more extensive cerebral infarcts.
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Isquemia Encefálica/fisiopatología , Calidad de Vida , Accidente Cerebrovascular/fisiopatología , Adulto , Anciano , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Encuestas y CuestionariosRESUMEN
The efficacy of 0.5% moxidectin pour-on in cows with naturally acquired nematode infections was evaluated. The study was carried out in a ranch in Veracruz, Mexico. Four groups of 15 cows were randomly allocated. Animals in the treated group received 0.5% moxidectin pour-on at a dose of 0.5 mg/kg body weight on a single occasion. The other two groups remained as untreated controls. Fecal samples from all cattle were taken on days 0 (pre-treatment), 7, 14, 28 and 60 (post-treatment, PT). Fecal egg-counts were determined using a modified McMaster technique and fecal cultures were performed to identify gastrointestinal nematodes infected larvae (L(3)). Treatment with moxidectin was associated with a significant reduction in fecal trichostrongyle egg-counts compared with the controls; efficacy was 100% at 28 days PT. Haemonchus spp. and Strongyloides spp. were the two genera identified from coprocultures.
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Antinematodos/administración & dosificación , Enfermedades de los Bovinos/tratamiento farmacológico , Enfermedades de los Bovinos/parasitología , Enfermedades Gastrointestinales/veterinaria , Nematodos/crecimiento & desarrollo , Infecciones por Nematodos/veterinaria , Administración Tópica , Animales , Bovinos , Heces/parasitología , Femenino , Enfermedades Gastrointestinales/tratamiento farmacológico , Enfermedades Gastrointestinales/parasitología , Macrólidos/administración & dosificación , México , Infecciones por Nematodos/tratamiento farmacológico , Infecciones por Nematodos/parasitología , Recuento de Huevos de Parásitos/veterinaria , Estadísticas no Paramétricas , Clima TropicalRESUMEN
Melanins are implicated in the pathogenesis of several human diseases, including some microbial infections. In this study, we analyzed whether the conidia and the yeasts of the thermally dimorphic fungal pathogen Paracoccidioides brasiliensis produce melanin or melanin-like compounds in vitro and during infection. Growth of P. brasiliensis mycelia on water agar alone produced pigmented conidia, and growth of yeasts in minimal medium with L-3,4-dihydroxyphenylalanine (L-DOPA) produced pigmented cells. Digestion of the pigmented conidia and yeasts with proteolytic enzymes, denaturant, and hot concentrated acid yielded dark particles that were the same size and shape as their propagules. Immunofluorescence analysis demonstrated reactivity of a melanin-binding monoclonal antibody (MAb) with the pigmented conidia, yeasts, and particles. Electron spin resonance spectroscopy identified the yeast-derived particles produced in vitro when P. brasiliensis was grown in L-DOPA medium as a melanin-like compound. Nonreducing polyacrylamide gel electrophoresis of cytoplasmic yeast extract revealed a protein that catalyzed melanin synthesis from L-DOPA. The melanin binding MAb reacted with yeast cells in tissue from mice infected with P. brasiliensis. Finally digestion of infected tissue liberated particles reactive to the melanin binding MAb that had the typical morphology of P. brasiliensis yeasts. These data strongly suggest that P. brasiliensis propagules, both conidia and yeast cells, can produce melanin or melanin-like compounds in vitro and in vivo. Based on what is known about the function of melanin in the virulence of other fungi, this pigment may play a role in the pathogenesis of paracoccidioidomycosis.
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Melaninas/metabolismo , Paracoccidioides/crecimiento & desarrollo , Paracoccidioides/patogenicidad , Paracoccidioidomicosis/microbiología , Animales , Medios de Cultivo , Espectroscopía de Resonancia por Spin del Electrón , Lacasa , Levodopa/metabolismo , Pulmón/metabolismo , Pulmón/microbiología , Masculino , Ratones , Ratones Endogámicos BALB C , Microscopía Electrónica de Rastreo , Oxidorreductasas/metabolismo , Paracoccidioides/metabolismo , Bazo/metabolismo , Bazo/microbiología , VirulenciaRESUMEN
The precise microenvironment of Paracoccidioides brasiliensis has not yet been discovered perhaps because the methods used are not sensitive enough. We applied to this purpose the polymerase chain reaction (PCR) using three sets of specific primers corresponding to two P. brasiliensis genes. This fungus as well as several other fungi, were grown and their DNA obtained by mechanical disruption and a phenol chloroform isoamylalcohol-based purification method. The DNA served for a PCR reaction that employed specific primers from two P. brasiliensis genes that codify for antigenic proteins, namely, the 27 kDa and the 43 kDa. The lowest detection range for the 27 kDa gene was 3 pg. The amplification for both genes was positive only with DNA from P. brasiliensis; additionally, the mRNA for the 27 kDa gene was present only in P. brasiliensis, as indicated by the Northern analysis. The standardization of PCR technology permitted the amplification of P. brasiliensis DNA in artificially contaminated soils and in tissues of armadillos naturally infected with the fungus. These results indicate that PCR technology could play an important role in the search for P. brasiliensis' habitat and could also be used in other ecological studies.
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Animales , Femenino , Masculino , Ratones , ADN de Hongos/genética , Cartilla de ADN , Ecosistema , Paracoccidioides , Reacción en Cadena de la Polimerasa/métodos , Armadillos , Secuencia de Bases , Northern Blotting , ADN de Hongos/aislamiento & purificación , Ratones Endogámicos BALB C , Paracoccidioides , Reacción en Cadena de la Polimerasa/normas , ARN MensajeroRESUMEN
Histoplasmosis is an important systemic fungal infection, particularly among immunocompromised individuals, who may develop a progressive disseminated form which is often fatal if it is untreated. In such patients, the detection of antibody responses for both diagnosis and follow-up may be of limited use, whereas the detection of Histoplasma capsulatum var. capsulatum antigens may provide a more practical approach. We have recently described an inhibition enzyme-linked immunosorbent assay (ELISA) for the detection in patients' sera of a 69- to 70-kDa H. capsulatum var. capsulatum-specific antigen which appears to be useful in diagnosis. To investigate its potential for the follow-up of histoplasmosis patients during treatment, antigen titers in the sera of 16 patients presenting with different clinical forms of histoplasmosis were monitored at regular intervals for up to 80 weeks. Sera from four of five patients with the acute form of the disease showed rapid falls in antigenemia, becoming antigen negative by week 14 (range, weeks 10 to 16). Sera from four patients with disseminated histoplasmosis showed falls in antigen levels; three of them became antigen negative by week 32; the fourth patient became negative by week 48. In contrast, antigen titers in four of six AIDS patients with the disseminated form of the disease remained positive throughout follow-up. Sera from only one patient who presented with the chronic form of the disease were analyzed, and this individual's serum became antigen negative by week 9. The inhibition ELISA is shown to be of particular use in the monitoring of non-AIDS patients with the acute and disseminated forms of the disease and may complement existing means of follow-up.
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Infecciones Oportunistas Relacionadas con el SIDA/diagnóstico , Antifúngicos/uso terapéutico , Antígenos Fúngicos/sangre , Fungemia/diagnóstico , Histoplasma/aislamiento & purificación , Histoplasmosis/diagnóstico , Histoplasmosis/tratamiento farmacológico , Itraconazol/uso terapéutico , Infecciones Oportunistas Relacionadas con el SIDA/sangre , Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Adolescente , Adulto , Anfotericina B/uso terapéutico , Niño , Preescolar , Ensayo de Inmunoadsorción Enzimática , Femenino , Estudios de Seguimiento , Fungemia/sangre , Fungemia/tratamiento farmacológico , Histoplasmosis/sangre , Humanos , Lactante , Masculino , Sensibilidad y Especificidad , Factores de TiempoRESUMEN
The microniche of the dimorphic fungus Paracoccidiodes brasiliensisremains undefined in spite of the many attempts to isolate it from natural sources. Until recently, knowledge was also scanty concerning the presence of natural infections in animals; however, in the last decade, the fungus has been repeatedly isolated from the nine-banded armadillo, Dasypus novemcinctusin Brazil. A study aimed at determining the presence of infected armadillos in one of the paracoccidioidomycosis endemic areas of Colombia (Manizales, Department of Caldas) was undertaken. Based on the records of paracoccidioidomycosis patients available in the regional hospital, we selected a locality corresponding to a permanent resident, and found that it also had armadillo's burrows. Counting with the proper authorization, two animals were captured, sacrificed under prolonged anaesthesia and various internal organs cultured in mycological media. PCR with specific P. brasiliensis'primers was also done. The fungus was isolated from the mesenteric lymph node of one of the animals; fungal DNA amplification was positive in the same specimen as well as in the liver. The isolate from the Colombian armadillo indicates that these animals are regular hosts to P. brasiliensis in at least two endemic countries. Due to the restricted life pattern of these mammals they represent an important link with the natural habitat of the fungus. Consequently, a study of their movements and habits could prove rewarding in the search for this habitat.
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The precise microenvironment of Paracoccidioides brasiliensis has not yet been discovered perhaps because the methods used are not sensitive enough. We applied to this purpose the polymerase chain reaction (PCR) using three sets of specific primers corresponding to two P. brasiliensis genes. This fungus as well as several other fungi, were grown and their DNA obtained by mechanical disruption and a phenol chloroform isoamylalcohol-based purification method. The DNA served for a PCR reaction that employed specific primers from two P. brasiliensis genes that codify for antigenic proteins, namely, the 27 kDa and the 43 kDa. The lowest detection range for the 27 kDa gene was 3 pg. The amplification for both genes was positive only with DNA from P. brasiliensis; additionally, the mRNA for the 27 kDa gene was present only in P. brasiliensis, as indicated by the Northern analysis. The standardization of PCR technology permitted the amplification of P. brasiliensis DNA in artificially contaminated soils and in tissues of armadillos naturally infected with the fungus. These results indicate that PCR technology could play an important role in the search for P. brasiliensis' habitat and could also be used in other ecological studies.
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Cartilla de ADN/genética , ADN de Hongos/genética , Ecosistema , Paracoccidioides/genética , Reacción en Cadena de la Polimerasa/métodos , Animales , Armadillos/microbiología , Secuencia de Bases , Northern Blotting , ADN de Hongos/aislamiento & purificación , Femenino , Masculino , Ratones , Ratones Endogámicos BALB C , Paracoccidioides/aislamiento & purificación , Reacción en Cadena de la Polimerasa/normas , ARN Mensajero/aislamiento & purificaciónRESUMEN
Paracoccidioidomycosis (PCM) is one of the most important endemic mycoses in Latin America; it is usually diagnosed by observation and/or isolation of the etiologic agent, Paracoccidioides brasiliensis, as well as by a variety of immunological methods. Although the latter are effective, two circumstances, cross-reactions with other mycotic agents and antigen preparation that is marked by extreme variability among lots, hinder proper standardization of the procedures. To circumvent this lack of reproducibility, molecular biology tools were used to produce a recombinant 27-kDa-molecular-mass antigen from this fungus; a sizable quantity of this antigen was obtained through fermentation of Escherichia coli DH5alpha, which is capable of expressing the fungal protein. The latter was purified by the Prep-Cell System (Bio-Rad); the recovery rate of the pure protein was approximately 6%. A battery of 160 human serum samples, consisting of 64 specimens taken at the time of diagnosis from patients with PCM representing the various clinical forms plus 15 serum specimens each from patients with histoplasmosis and aspergillosis, 10 each from patients with cryptococcosis and tuberculosis, 6 from patients with coccidioidomycosis, and 40 from healthy subjects, were all tested by an indirect enzyme-linked immunosorbent assay with the purified 27-kDa recombinant protein. The latter was used at a concentration of 1.0 microgram/well; there were three serum dilutions (1:1,000, 1:2,000, and 1:4,000). The experiment was repeated at least twice. The average sensitivity for both experiments was 73.4%; in comparison with the healthy subjects, the specificity for PCM patients was 87.5% while for patients with other mycoses, it was 58.7%. Important cross-reactions with sera from patients with aspergillosis and histoplasmosis were detected. The positive predictive value of the test was 90.4%. These results indicate that it is possible to employ recombinant antigenic proteins for the immunologic diagnosis of PCM and, by so doing, achieve high coverage rates. Furthermore, antigen reproducibility can now be ensured, thus facilitating inter- and intralaboratory standardization.
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Anticuerpos Antifúngicos/sangre , Antígenos Fúngicos/inmunología , Paracoccidioides/inmunología , Paracoccidioidomicosis/diagnóstico , Antígenos Fúngicos/genética , Ensayo de Inmunoadsorción Enzimática , Escherichia coli/genética , Escherichia coli/crecimiento & desarrollo , Escherichia coli/metabolismo , Fermentación , Humanos , Paracoccidioides/genética , Valor Predictivo de las Pruebas , Proteínas Recombinantes/genética , Proteínas Recombinantes/inmunología , Sensibilidad y Especificidad , Transformación GenéticaRESUMEN
Serological diagnosis and follow-up of paracoccidioidomycosis (PCM) patients have relied mainly on the detection of antibody responses by using techniques such as complement fixation (CF) and immunodiffusion. We recently described a novel inhibition enzyme-linked immunosorbent assay (inh-ELISA) which proved to be useful in the diagnosis of PCM via the detection of an 87-kDa determinant in patient sera (B. L. Gomez, J. I. Figueroa, A. J. Hamilton, B. Ortiz, M. A. Robledo, R. J. Hay, and A. Restrepo, J. Clin. Microbiol. 35:3278-3283, 1997). This test has now been assessed as a means of following up PCM patients. A total of 24 PCM patients, classified according to their clinical presentation (6 with the acute form of the disease, of whom two had AIDS, 12 with the multifocal form of the disease, and 6 with the unifocal form of the disease), were studied. The four human immunodeficiency virus-negative patients with acute PCM showed a statistically significant decrease in circulating antigen levels after the start of antifungal therapy. Antigen levels in this group became negative by our criteria (=2.3 microgram/ml) before week 20 and remained so in three of four of these patients. In contrast, the two AIDS patients who also presented with the acute form of PCM showed no statistically significant decrease in circulating antigen levels even after 68 weeks of therapy. Taken together as a group, the patients with the multifocal form showed a statistically significant decrease in antigenemia after 28 weeks of therapy. In addition, five of six patients with the unifocal form became antigen negative by week 40. Antigen level decrease mirrored clinical cure in the majority of patients in all clinical groups; in contrast, measurement of anti-PCM antibodies via the CF test showed wide fluctuations in titers during the follow-up period. The inh-ELISA for the detection of the 87-kDa Paracoccidioides brasiliensis determinant would appear to be a valuable additional tool in the follow-up of PCM patients.