ABSTRACT
The Receptor Binding Domain (RBD) of SARS-CoV-2, the virus responsible for the COVID-19 pandemic, is the functional region of the viral Spike protein (S), which is involved in cell attachment to target cells. The virus has accumulated progressively mutations in its genome, particularly in the RBD region, many of them associated with immune evasion of the host neutralizing antibodies. Some of the viral lineages derived from this evolution have been classified as Variant of Interest (VOI) or Concern (VOC). The neutralizing capacity of a F(ab')2 preparation from sera of horses immunized with viral RBD was evaluated by lytic plaque reduction assay against different SARS-CoV-2 variants. A F(ab')2 preparation of a hyperimmune serum after nine immunizations with RBD exhibited a high titer of neutralizing antibodies against the ancestral-like strain (1/18,528). A reduction in the titer of the F(ab')2 preparation was observed against the different variants tested compared to the neutralizing activity against the ancestral-like strain. The highest reduction in the neutralization titer was observed for the Omicron VOC (4.7-fold), followed by the Mu VOI (2.6), Delta VOC (1.8-fold), and Gamma VOC (1.5). Even if a progressive reduction in the neutralizing antibodies titer against the different variants evaluated was observed, the serum still exhibited a neutralizing titer against the Mu VOI and the Omicron VOC (1/7113 and 1/3918, respectively), the evaluated strains most resistant to neutralization. Therefore, the preparation retained neutralizing activity against all the strains tested.
ABSTRACT
Brachybacterium conglomeratum, traditionally considered an environmental bacterium, has recently garnered attention for its potential involvement in human health. While prior research hinted at its pathogenic role in humans, our study aims to determine its prevalence and associations in diverse clinical contexts. We examined vaginal swabs from three distinct patient groups: patients with low-grade squamous intraepithelial lesions (LSIL), patients with cervicovaginal infections, and patients with a history of precancerous lesions undergoing follow-up. B. conglomeratum was present in all three patient groups, with the highest prevalence observed in the LSIL group. Statistically significant associations were primarily identified in the LSIL group, where B. conglomeratum was present in 60% of cases. Notably, the LSIL group exhibited coinfections with multiple high-risk oncogenotypes of human papillomavirus (HPV), suggesting potential synergistic effects, and understanding these microbial relationships and their influence on viral persistence, particularly with HPV, holds promise for mitigating HPV-related carcinogenesis. Furthermore, Gardnerella vaginalis and Atopobium vaginae were frequently detected in this group, along with Ureaplasma parvum as the predominant sexually transmitted bacterium. In all cases, B. conglomeratum was found in association with these microorganisms rather than as a sole pathogen. This coexistence underscores the intricate microbial interactions within cervicovaginal infections and precancerous lesions. This study marks the first report of B. conglomeratum prevalence in women with these clinical conditions.
ABSTRACT
Abstract Crotalid envenomation is a neglected collective health problem involving many countries in America, which need secure and inexpensive snake anti-venom treatments. Here, high antibody titers (IgY) were raised in the Ostrich (Struthio camelus) egg yolk by immunizing with the venom of Venezuelan venomous Crotalus snakes. Ostriches were immunized with a pool of venoms from common rattlesnake (Crotalus durissus cumanensis), Uracoan rattlesnake (Crotalus vegrandis), Guayana rattlesnake (Crotalus durissus ruruima) and black rattlesnake (Crotalus pifanorum). The anti-snake venom antibodies were prepared from egg yolk by the water dilution method, enriched by the addition of caprylic acid (CA) and precipitation with ammonium sulfate at 30% (W/V). The purity and molecular mass of the final product was satisfactory, yielding a single ∼ 175 kDa band in SDS-PAGE gels ran under non-reducing conditions. In the immunoblot analysis, specific binding of the antivenom was observed with most venom proteins. The LD50 was 16.5 g/mouse (825 μg/kg body weight). High titers of IgY against Crot/pool venom were shown by ELISA. The median effective dose (ED50) was 19.66 mg/2LD50. IgY antibodies neutralized efficiently the Crot/pool venom lethality. As far as we know, this is the first anti-snake venom produced in ostriches, which could make this technology an affordable alternative for low-income countries, since it is likely to produce manteniabout 2-4 g of IgY per ostrich egg. Hence, almost 400 g of IgY can be purified from only one ostrich during a year. In addition, there are enormous differences in the cost of investment in the maintenance of horses, from the points of view of infrastructure, feeding and veterinary care, in which the cost can reach USD 100 per animal per day, compared to a maintenance cost of USD 146 per month per producing bird. These results are encouraging and could easily be extrapolated to the manufacturing of other antivenoms and antitoxins as well, as they could be applied to the manufacturing of potential diagnostic tools.
Resumen El envenenamiento por crotálidos es un problema de salud colectiva desatendido, que involucra a muchos países del continente americano, los cuales necesitan tratamientos seguros y económicos. En este trabajo, se obtuvieron títulos altos de anticuerpos (IgY) producidos en yema de huevo de avestruz (Struthio camelus) mediante la inmunización con el veneno de serpientes venezolanas del genero Crotalus. Se inmunizaron avestruces con una colección de veneno de serpientes de cascabel común (Crotalus durissus cumanensis), cascabel de Uracoa (Crotalus vegrandis), cascabel de Guayana (Crotalus durissus ruruima) y cascabel negra (Crotalus pifanorum). Los anticuerpos anti-veneno de serpiente se prepararon a partir de yema de huevo por el método de dilución en agua, enriquecidos mediante la adición de ácido caprílico (CA), seguido de una precipitación con sulfato de amonio al 30% (P/V). La pureza y masa molecular de los anticuerpos (IgY) se definieron mediante ensayos de SDS-PAGE nativos y las masas moleculares se establecieron electroforéticamente, obteniéndose una única banda de IgY de ∼ 175 kDa. El análisis de inmunotransferencia mostró la unión específica del antiveneno con la mayoría de las proteínas del veneno. La DL50 fue de 16,5 μg/ratón (825 μg / kg de peso corporal); Se mostraron títulos altos de IgY contra el veneno de Crot / pool mediante ELISA. La dosis mediana efectiva (DE50) fue de 19,66 mg/2 LD50. Los anticuerpos IgY neutralizaron eficazmente la letalidad del veneno de Crot / pool. Hasta donde sabemos, se trata del primer antídoto de serpiente producido en avestruces, lo que podría abaratar la producción de este tratamiento en países del tercer mundo. Ya que es probable que se obtengan alrededor de 2-4 g de IgY por huevo de avestruz. Por lo tanto, se podrían purificar casi 400 g de IgY de un solo avestruz durante un año. Asimismo, debido a las enormes diferencias en el costo de inversión en el mantenimiento de los caballos desde el punto de vista de infraestructura, alimentación y atención veterinaria, en los que el costo puede llegar a los 100 USD por día, frente a los 146 USD por mes de mantenimiento de la producción de aves. Estos resultados abren un campo terapéutico, para la fabricación de otros antivenenos contra un amplio espectro de toxinas y también como probables herramientas de diagnóstico.
ABSTRACT
Resumen En esta revisión de la literatura presentamos diversos mecanismos terapéuticos para tratar la rigidez vascular en pacientes con enfermedad renal crónica. En el ámbito de la terapéutica no farmacológica la restricción de sodio y la indicación de dieta mediterránea han demostrado efectos benéficos, mientras que acerca de la indicación de actividad física aún no hay evidencia clara sobre su utilidad para disminuir la rigidez vascular en este grupo específico de pacientes. Es con el tratamiento farmacológico donde se evidencian los mayores beneficios, tanto en la rigidez vascular como en los eventos cardiovasculares asociados. Está ampliamente demostrada la efectividad de los inhibidores del sistema renina-angiotensina-aldosterona y de los fármacos antialdosterónicos para disminuir la presión y la rigidez arterial. Otras drogas, como los bloqueadores del receptor de endotelina, han demostrado sus efectos protectores sobre la pared arterial, aunque no están carentes de potenciales efectos adversos. También repasamos los resultados obtenidos con el uso de las nuevas drogas antidiabéticas, en particular los iSLGT2 y los aGLP-1, y su efecto sobre la presión arterial y la rigidez vascular, en particular en pacientes con enfermedad renal crónica. Se revisan además la utilidad de aquellas drogas con efecto sobre la cascada inflamatoria y sobre las calcificaciones vasculares, muy propensas durante los tratamientos sustitutivos de la función renal. Este trabajo se enfoca, en síntesis, en las diversas intervenciones terapéuticas sobre la rigidez arterial, con énfasis en la disminución de eventos cardiovasculares y de la mortalidad en pacientes con enfermedad renal crónica.
Abstract In this literature review we present various therapeutic alternatives for vascular stiffness in patients with chronic kidney disease. Here we discussed the role of non-pharmacological treatments with evidence of the benefit of sodium restriction on vascular stiffness, the positive effects in that sense shown by the Mediterranean diet, and the small benefits of physical activity on vascular stiffness in this group of patients. Is in the pharmacological treatment where the best benefits are evidenced; both, on vascular stiffness and on the associated cardiovascular events. The effectiveness of renin-angiotensin-aldosterone system inhibitors and antialdosteronic drugs to decrease blood pressure and stiffness has been widely demonstrated. Other drugs, such as endothelin receptor blockers, showed their protective effects on the arterial wall, but with potential adverse effects. This article also reviews the effects of new anti-diabetic drugs, iSLGT2 and aGLP-1 in particular, and their effect on blood pressure and vascular stiffness, particularly in patients with chronic kidney disease. The utility of drugs with effects on the inflammatory cascade and drugs with a potential effect on vascular calcification, complication occurring frequently during renal function replacement treatment, are also reviewed. In short, this work focuses in the therapeutic interventions on arterial stiffness, with emphasis on the reduction of cardiovascular events and mortality in patients with chronic kidney disease.
ABSTRACT
Wilms tumor (WT) is the most frequently diagnosed malignant renal tumor in children. With current treatments, ~90% of children diagnosed with WT survive and generally present with tumors characterized by favorable histology (FHWT), whereas prognosis is poor for the remaining 10% of cases where the tumors are characterized by cellular diffuse anaplasia (DAWT). Relatively few studies have investigated microRNA-related epigenetic regulation and its relationship with altered gene expression in WT. Here, we aim to identify microRNAs differentially expressed in WT and describe their expression in terms of cellular anaplasia, metastasis, and association with the main genetic alterations in WT to identify potential prognostic biomarkers. Expression profiling using TaqMan low-density array was performed in a discovery cohort consisting of four DAWT and eight FHWT samples. Relative quantification resulted in the identification of 109 (48.7%) microRNAs differentially expressed in both WT types. Of these, miR-10a-5p, miR-29a-3p, miR-181a-5p, miR-200b-3p, and miR-218-5p were selected and tested by RT-qPCR on a validation cohort of 53 patient samples. MiR-29a and miR-218 showed significant differences in FHWT with low (P = 0.0018) and high (P = 0.0131) expression, respectively. To discriminate between miRNA expression FHWTs and healthy controls, the receiver operating characteristic (ROC) curves were obtained; miR-29a AUC was 0.7843. Furthermore, low expression levels of miR-29a and miR-200b (P = 0.0027 and P = 0.0248) were observed in metastatic tumors. ROC curves for miR-29a discriminated metastatic patients (AUC = 0.8529) and miR-200b (AUC = 0.7757). To confirm the differences between cases with poor prognosis, we performed in situ hybridization for three microRNAs in five DAWT and 17 FHWT samples, and only significant differences between adjacent tissues and FHWT tumors were found for miR-181a, miR-200b, and miR-218, in both total pixels and nuclear analyses. Analysis of copy number variation in genes showed that the most prevalent alterations were WTX (47%), IGF2 (21%), 1q (36%) gain, 1p36 (16%), and WTX deletion/1q duplicate (26%). The five microRNAs evaluated are involved in the Hippo signaling pathway and participate in Wilms tumor development through their effects on differentiation, proliferation, angiogenesis, and metastasis.
ABSTRACT
Resumen Existen cambios estructurales importantes de la pared arterial en, prácticamente, todas las etapas clínicas de la enfermedad renal crónica. Son un marcador pronóstico y, al mismo tiempo, un factor de progresión y de eventos, tanto cardiovasculares como renales. Es por ello que tener una estimación del daño vascular y, mejor aún, un diagnóstico adecuado es esencial. La evaluación vascular en la consulta clínica, mediante la determinación de la presión del pulso y el índice de presión arterial sistólica tobillo-brazo, sirven como una orientación inicial del daño arterial de estos pacientes. Hoy podemos valorar, de manera accesible, las lesiones estructurales de las arterias mediante la cuantificación y caracterización, por ecografía vascular, de las placas ateroscleróticas de carótidas y femorales y por la velocidad de onda del pulso. En la gran mayoría de los pacientes renales la velocidad de onda del pulso está muy aumentada, comparada con poblaciones sanas, como consecuencia de múltiples mecanismos patogénicos. Las alteraciones vasculares, tanto de los grandes vasos como de la microcirculación, están fuertemente vinculados con la progresión de la enfermedad renal crónica, así como con complicaciones y eventos renales, cardiacos y cerebrales. En conclusión, en individuos con riesgo de desarrollar enfermedad renal crónica, o en quienes ya la padecen, la medición de la rigidez arterial y de los daños ateroscleróticos de la pared vascular serían parámetros centrales para su evaluación y uno de los objetivos a considerar al diseñar estrategias preventivas del deterioro de los órganos blanco y eventos.
Abstract There exist significant structural changes in the artery wall in almost all clinical stages of chronic kidney disease. They constitute a prognostic marker and, at the same time, a progression factor and an event factor, both cardiovascular and renal. For that reason, it is essential to have an estimation of vascular damage and, even better, an accurate diagnosis. Vascular evaluation during clinical consultation by means of determining pulse pressure and ankle-brachial pressure index are a helpful initial orientation of these patient´s artery damage. Today we can assess, in an accessible way, the structural lesions of the arteries by means of quantification and characterization, through vascular ultrasound, of carotid and femoral atherosclerotic plaques and through the pulse wave velocity. The vast majority of renal patients show increased pulse wave velocity, compared to healthy populations, as a result of multiple pathogenic mechanisms. Vascular alterations, both of large arteries and at the microcirculation level, are strongly linked to the progression of chronic kidney disease, as well as renal, cardiac and cerebral complications and events. In individuals at risk of developing chronic kidney disease, or in those who already suffer from it, the measurement of arterial stiffness and of atherosclerotic damage to the vascular wall is a central parameter for evaluation and one of the objectives to consider when designing preventive strategies against deterioration of target organs and events.
ABSTRACT
Two siblings from a Mexican family who carried lethal Raine syndrome are presented. A newborn term male (case 1) and his 21 gestational week brother (case 2), with a similar osteosclerotic pattern: generalized osteosclerosis, which is more evident in facial bones and cranial base. Prenatal findings at 21 weeks and histopathological features for case 2 are described. A novel combination of biallelic FAM20C pathogenic variants were detected, a maternal cytosine duplication at position 456 and a paternal deletion of a cytosine in position 474 in exon 1, which change the reading frame with a premature termination at codon 207 and 185 respectively. These changes are in concordance with a negative detection of the protein in liver and kidney as shown in case 2. Necropsy showed absence of pancreatic Langerhans Islets, which are reported here for the first time. Corpus callosum absence is added to the few reported cases of brain defects in Raine syndrome. This report shows two new FAM20C variants not described previously, and negative protein detection in the liver and the kidney. We highlight that lethal Raine syndrome is well defined as early as 21 weeks, including mineralization defects and craniofacial features. Pancreas and brain defects found here in FAM20C deficiency extend the functional spectrum of this protein to previously unknown organs.
Subject(s)
Abnormalities, Multiple/genetics , Casein Kinase I/genetics , Cleft Palate/genetics , Exophthalmos/genetics , Extracellular Matrix Proteins/genetics , Microcephaly/genetics , Osteosclerosis/genetics , Abnormalities, Multiple/metabolism , Bone Diseases, Developmental , Casein Kinase I/metabolism , Cleft Palate/metabolism , Cysteine/genetics , Exophthalmos/metabolism , Extracellular Matrix Proteins/metabolism , Family , Female , Humans , Infant, Newborn , Islets of Langerhans/pathology , Kidney/pathology , Liver/pathology , Male , Microcephaly/metabolism , Mutation , Osteosclerosis/metabolism , Pedigree , Phenotype , Polymorphism, Genetic/geneticsABSTRACT
Resumen La relación corazón-riñón concentra especial interés entre la población médica, dado que su interacción es de alto impacto sobre la salud, y su relación es amplia y compleja.La enfermedad renal crónica genera cambios en la estructura y función vascular de gran repercusión hemodinámica. El endurecimiento arterial producto de la inflamación vascular genera cambios en el acoplamiento ventrículo/arterial con la consecuente alteración en la perfusión tisular y en el trabajo ventricular izquierdo. La insuficiencia renal crónica genera la activación de una cascada inflamatoria responsable de la alteración del endotelio y el aumento del tono/grosor de la capa media arterial. Paralelamente, el desbalance autonómico, la acumulación de mediadores pro inflamatorios y pro fibróticos, colaboran también en la alteración de la estructura y función vascular.En la modificación de las propiedades mecánicas del sistema arterial, encontramos un mecanismo fundamental de alteración en la perfusión tisular, en particular de los lechos de baja resistencia como cerebro y riñón, siendo responsables de deterioro cognitivo y progresión del daño renal.El aumento de la postcarga del ventrículo izquierdo genera aumento del trabajo ventricular con el consiguiente desarrollo de hipertrofia e insuficiencia. El propósito de este artículo es realizar una revisión de los procesos descriptos, integrarlos en una lógica fisiopatológica y proveer una idea clara del impacto de la enfermedad renal crónica en el daño cardiovascular.
Abstract The heart-kidney relation generates special interest among the medical population given that this interaction has a strong impact on health and is wide and complex. Chronic kidney disease causes changes in the vascular structure and function with a major hemodynamic repercussion. Arterial hardening resulting from vascular inflammation produces changes in the ventricular-arterial coupling and, as a consequence, the alteration of tissue perfusion and left ventricle function. Chronic renal failure activates an inflammatory cascade which generates endothelium alteration and increases the tone/thickness of the artery medial layer. At the same time, the autonomic imbalance and the accumulation of pro-inflammatory and profibrotic mediators also contribute to the alteration of vascular structure and function. Among the changes in the mechanical properties of the artery system, a fundamental mechanism of tissue perfusion is found, particularly, in low-resistance beds such as the brain and kidney, responsible for cognitive deterioration and kidney damage progression. Increased left ventricular afterload causes higher ventricular work leading to hypertrophy and failure. The aim of this article is to make a revision of the processes described, integrate them into a physiopathological logic and give a clear idea of the impact of CKD upon cardiovascular damage.
ABSTRACT
En pacientes con malformaciones congénitas y retraso del desarrollo psicomotor, deben descartarse cromosomopatías. Las más frecuentes son las translocaciones recíprocas balanceadas, presentes en 1:500 recién nacidos vivos. Por lo general, los portadores tienen fenotipo normal, aunque, ocasionalmente, presentan infertilidad, abortos o hijos con malformaciones. La translocación balanceada entre los cromosomas 2 y 9 puede originar descendencia con monosomías y trisomías de estos cromosomas. La monosomía del brazo corto del cromosoma 9 puede presentarse con trigonocefalia, dismorfias faciales, anomalías genitales y retraso del desarrollo psicomotor. En este trabajo, se revisaron las alteraciones de los cromosomas 2 y/o 9 en los cariotipos realizados en nuestra Institución en 2005-2014. Se presentan dos pacientes con monosomía 9p asociada a translocación (2;9). Las pacientes comparten datos de monosomía 9p24-pter; la correlación genotipo-fenotipo es compleja por el tamaño de los segmentos involucrados. Se resalta la importancia del diagnóstico cromosómico para el asesoramiento genético.
In patients with malformations and delayed psychomotor development it is important to discard chromosomopathies. Balanced reciprocal translocations are the most frequent chromosomopathies present in 1:500 live newborns. In general, carriers have normal phenotype, but they may have infertility, abortions or children with congenital malformations. The reciprocal translocation between chromosomes 2 and 9 can lead to offspring with monosomies and trisomies of these chromosomes. Short arm monosomy of chromosome 9 may present delayed psychomotor development, trigonocephaly, facial dysmorphia and genital abnormalities. We reviewed GTG karyotype records from our Institution to identify cases with chromosomes 2 and/or 9 alterations from 2005 to 2014. We describe two cases with monosomy 9p secondary to a translocation between chromosomes 2 and 9. The patients share features of monosomy 9p24-pter, however the genotype-phenotype correlation is complex due to the extension of the involved segments. We emphasize the importance of chromosomal diagnosis to offer genetic assessment.
Subject(s)
Humans , Female , Infant, Newborn , Child, Preschool , Translocation, Genetic , Chromosome Disorders/diagnosis , Phenotype , Chromosomes, Human, Pair 9/genetics , Chromosome Deletion , Chromosome Disorders/genetics , Genotype , KaryotypingABSTRACT
In patients with malformations and delayed psychomotor development it is important to discard chromosomopathies. Balanced reciprocal translocations are the most frequent chromosomopathies present in 1:500 live newborns. In general, carriers have normal phenotype, but they may have infertility, abortions or children with congenital malformations. The reciprocal translocation between chromosomes 2 and 9 can lead to offspring with monosomies and trisomies of these chromosomes. Short arm monosomy of chromosome 9 may present delayed psychomotor development, trigonocephaly, facial dysmorphia and genital abnormalities. We reviewed GTG karyotype records from our Institution to identify cases with chromosomes 2 and/or 9 alterations from 2005 to 2014. We describe two cases with monosomy 9p secondary to a translocation between chromosomes 2 and 9. The patients share features of monosomy 9p24-pter, however the genotypephenotype correlation is complex due to the extension of the involved segments. We emphasize the importance of chromosomal diagnosis to offer genetic assessment.
En pacientes con malformaciones congénitas y retraso del desarrollo psicomotor, deben descartarse cromosomopatías. Las más frecuentes son las translocaciones recíprocas balanceadas, presentes en 1:500 recién nacidos vivos. Por lo general, los portadores tienen fenotipo normal, aunque, ocasionalmente, presentan infertilidad, abortos o hijos con malformaciones. La translocación balanceada entre los cromosomas 2 y 9 puede originar descendencia con monosomías y trisomías de estos cromosomas. La monosomía del brazo corto del cromosoma 9 puede presentarse con trigonocefalia, dismorfias faciales, anomalías genitales y retraso del desarrollo psicomotor. En este trabajo, se revisaron las alteraciones de los cromosomas 2 y/o 9 en los cariotipos realizados en nuestra Institución en 2005-2014. Se presentan dos pacientes con monosomía 9p asociada a translocación (2;9). Las pacientes comparten datos de monosomía 9p24-pter; la correlación genotipo-fenotipo es compleja por el tamaño de los segmentos involucrados. Se resalta la importancia del diagnóstico cromosómico para el asesoramiento genético.
Subject(s)
Chromosome Disorders/diagnosis , Translocation, Genetic , Child, Preschool , Chromosome Deletion , Chromosome Disorders/genetics , Chromosomes, Human, Pair 9/genetics , Female , Genotype , Humans , Infant, Newborn , Karyotyping , PhenotypeABSTRACT
ABSTRACT Hyporeninemic hypoaldosteronism, despite being common, remains an underdiagnosed entity that is more prevalent in patients with diabetes mellitus. It presents with asymptomatic hyperkalemia along with hyperchloraemic metabolic acidosis without significant renal function impairment. The underlying pathophysiological mechanism is not fully understood, but it is postulated that either aldosterone deficiency (hyporeninemic hypoaldosteronism) and/or target organ aldosterone resistance (pseudohypoaldosteronism) may be responsible. Diagnosis is based on laboratory parameters. Treatment strategy varies according to the underlying pathophysiological mechanism and etiology and aims to normalize serum potassium. Two clínical cases are reported and the relevant literature is revisited.
RESUMO Apesar de comum, o hipoaldosteronismo hiporeninêmico continua a ser uma entidade sub-diagnosticada, com maior prevalência em pacientes com diabetes mellitus. A doença cursa com hipercalemia assintomática acompanhada de acidose metabólica hiperclorêmica sem disfunção renal significativa. O mecanismo fisiopatológico subjacente não é entendido em sua totalidade, mas postula-se que a deficiência de aldosterona (hipoaldosteronismo hiporeninêmico) e/ou a resistência à aldosterona no órgão-alvo (pseudo-hipoaldosteronismo) possam ser responsáveis. O diagnóstico é fundamentado em parâmetros laboratoriais. A estratégia terapêutica varia de acordo com o mecanismo fisiopatológico subjacente e a etiologia, mas seu objetivo é normalizar o potássio sérico. O presente artigo relata dois casos e analisa a literatura relevante sobre o assunto.
Subject(s)
Humans , Male , Middle Aged , Hypoaldosteronism/diagnosis , Diabetes Complications/diagnosis , Hyperkalemia/diagnosis , Hypoaldosteronism/complications , Hyperkalemia/complicationsABSTRACT
Hyporeninemic hypoaldosteronism, despite being common, remains an underdiagnosed entity that is more prevalent in patients with diabetes mellitus. It presents with asymptomatic hyperkalemia along with hyperchloraemic metabolic acidosis without significant renal function impairment. The underlying pathophysiological mechanism is not fully understood, but it is postulated that either aldosterone deficiency (hyporeninemic hypoaldosteronism) and/or target organ aldosterone resistance (pseudohypoaldosteronism) may be responsible. Diagnosis is based on laboratory parameters. Treatment strategy varies according to the underlying pathophysiological mechanism and etiology and aims to normalize serum potassium. Two clínical cases are reported and the relevant literature is revisited.
Subject(s)
Diabetes Complications/diagnosis , Hyperkalemia/diagnosis , Hypoaldosteronism/diagnosis , Humans , Hyperkalemia/complications , Hypoaldosteronism/complications , Male , Middle AgedABSTRACT
Resumen: Introducción: La sarcoidosis es una enfermedad sistémica de etiología desconocida que raramente se presenta en la infancia. Generalmente afecta los pulmones; sin embargo, puede involucrar diversos órganos. Ocasionalmente afecta el estado general, y origina fiebre, hepatomegalia y esplenomegalia. Caso clínico: Se presenta el caso de un adolescente de doce años de edad con sarcoidosis infantil de inicio tardío, cuyo diagnóstico fue confirmado con un estudio histopatológico de ganglio linfático. El paciente cursó con afección general, hipercalcemia, eritema nodoso, alteraciones pulmonares graves, adenopatías, hepatomegalia y masa testicular. Recibió tratamiento con esteroides, con excelente respuesta clínica. Conclusiones: Se resalta la importancia de considerar el diagnóstico de sarcoidosis en los pacientes con hepatomegalia, adenopatías, daño pulmonar difuso, eritema nodoso, masa testicular e hipercalcemia, así como la necesidad del abordaje multidisciplinario para valorar el compromiso orgánico múltiple y el inicio oportuno de la terapia con esteroides, con el fin de evitar la progresión de la enfermedad.
Abstract: Background: Sarcoidosis is a systemic disease of unknown etiology that rarely occurs in children. It usually affects the lungs, however, it may involve various organs. It occasionally affects the general condition, and causes fever, hepatomegaly and splenomegaly. Case report: We report the case of a twelve-year-old adolescent with late-onset childhood sarcoidosis which diagnosis was confirmed by lymph node histopathological study. The patient presented general condition, hypercalcemia, erythema nodosum, severe lung disorders, lymphadenopathy, hepatomegaly and testicular mass. He received treatment with steroids, with excellent clinical response. Conclusions: We highlight the importance of considering the diagnosis of sarcoidosis in patients with hepatomegaly, lymphadenopathy, diffuse lung damage, erythema nodosum, testicular mass and hypercalcemia, as well as the need for a multidisciplinary approach to assess multiple organ involvement and the early beginning of steroid treatment in order to prevent the progression of the disease.
ABSTRACT
BACKGROUND: Sarcoidosis is a systemic disease of unknown etiology that rarely occurs in children. It usually affects the lungs, however, it may involve various organs. It occasionally affects the general condition, and causes fever, hepatomegaly and splenomegaly. CASE REPORT: We report the case of a twelve-year-old adolescent with late-onset childhood sarcoidosis which diagnosis was confirmed by lymph node histopathological study. The patient presented general condition, hypercalcemia, erythema nodosum, severe lung disorders, lymphadenopathy, hepatomegaly and testicular mass. He received treatment with steroids, with excellent clinical response. CONCLUSIONS: We highlight the importance of considering the diagnosis of sarcoidosis in patients with hepatomegaly, lymphadenopathy, diffuse lung damage, erythema nodosum, testicular mass and hypercalcemia, as well as the need for a multidisciplinary approach to assess multiple organ involvement and the early beginning of steroid treatment in order to prevent the progression of the disease.
ABSTRACT
El Hospital Provincial Universitario Arnaldo Milián Castro posee una tradición importante en la conducción de investigaciones clínicas con productos del Centro de Inmunología Molecular y del Centro de Ingeniería Genética y Biotecnología. Hasta el momento el trabajo ha tenido como base las normas de Buenas PrácticasClínicas y los elementos del Sistema de Calidad del Centro Promotor; sin embargo, para lograr la conducción de ensayos clínicos con calidad y satisfacer las necesidades de los clientes internos y externos es necesario poseer un sistema de calidad propio. Se desarrolló un sistema de gestión de los procesos de evaluación y tratamiento de los pacientes incluidos en ensayos clínicos; se elaboró el sistemadocumental de esos procesos, los documentos fueron revisados, aprobados y se pusieron en práctica en las áreas de investigación involucradas en los procesos, con lo que aumentan los estándares de calidad para el sitio clínico y se cumplen las normas de Buenas Prácticas Clínicas(AU)
Subject(s)
Humans , Clinical Clerkship/standards , Clinical Trials, Phase I as TopicABSTRACT
Se exponen 3 casos con hallazgo incidental de páncreas heterotópico, en autopsia y 2 piezas quirúrgicas para hacer una breve revisión del tema. Casos: 1. Mujer de 53 años de edad fallecida por neumonía de focos múltiples. Durante el estudio post mortem se encontró, a nivel del segmento yeyunal, un nódulo constituido histológicamente por múltiples conductos con epitelio columnar y fibras anchas desorganizadas de músculo liso. 2. Preescolar varón de 2 años 11 meses de edad con diagnóstico de quiste de colédoco y resección del mismo. En uno de los cortes de pared se observó una banda de tejido que a la microscopía de luz correspondía a tejido pancreático sin alteraciones. 3. Escolar mujer de 6 años 10 meses de edad con diagnóstico de síndrome de Byler candidata a transplante hepático. Los cortes histológicos del explante en la región del hilio revelaron grupos multifocales de conductos y acinos pancreáticos sin presencia de islotes. Conclusión: La heterotopia pancreática es un hallazgo infrecuente que se puede observar a cualquier nivel del tracto gastrointestinal e inclusive fuera del mismo, por lo que la caracterización histopatológica de esta alteración permite distinguirla de otras lesiones. Pese a su conducta habitualmente benigna y asintomática, ocasionalmente puede dar origen a cuadros obstructivos, hemorrágicos, inflamatorios o neoplásicos.
We report three cases of pancreatic heterotopia incidentally found (one in autopsy and two in surgical pieces) with a brief review of the literature. Cases: 1. A fifty-three-year-old woman who died of bronchopneumonia. During post-mortem examination, a nodule (hystologically formed by multiple ducts lined by columnar epithelium and broad disarranged smooth muscle fibers) was found at the level of jejune. 2. 5-year, 11-month-old male with diagnosis ofcholedochal cyst. In the resected specimen, one of the mural slices showed a tissue stripe that under light-microscope examination corresponded to normal pancreatic tissue. 3. 6-year, 10-month-old female diagnosed with Byler syndrome who was recipient of liver transplant. Slices taken from the hilum in the resected specimen revealed multiple clusters of pancreatic acini and ducts without evidence of endocrine islets. Conclusion: Pancreatic heterotopia is an uncommon finding, which may be found at any level of the gastrointestinal tract, and even outside it. Histopathologic studies allow to distinguish this disorder from other lesions. Despite its commonly benign and asymptomatic behaviour, it may sometimes produce obstruction, hemorrhage, inflammation or neoplasms.