RESUMO
Monoclonal gammopathies (MG) are characterized by the proliferation of plasma cells that produce identical abnormal immunoglobulins (intact or some of their subunits). This abnormal immunoglobulin component is called monoclonal protein (M-protein), and is considered a biomarker of proliferative activity. The identification, characterization and measurement of M-protein is essential for the management of MG. We conducted a systematic review of the different tests and measurement methods used in the clinical laboratory for the study of M-protein in serum and urine, the biochemistry and hematology tests necessary for clinical evaluation, and studies in bone marrow, peripheral blood and other tissues. This review included literature published between 2009 and 2022. The paper discusses the main methodological characteristics and limitations, as well as the purpose and clinical value of the different tests used in the diagnosis, prognosis, monitoring and assessment of treatment response in MG. Included are methods for the study of M-protein, namely electrophoresis, measurement of immunoglobulin levels, serum free light chains, immunoglobulin heavy chain/light chain pairs, and mass spectrometry, and for the bone marrow examination, morphological analysis, cytogenetics, molecular techniques, and multiparameter flow cytometry.
Assuntos
Hematologia , Mieloma Múltiplo , Paraproteinemias , Humanos , Laboratórios Clínicos , Consenso , Paraproteinemias/diagnóstico , Paraproteinemias/terapia , Cadeias Leves de Imunoglobulina , Mieloma Múltiplo/diagnósticoRESUMO
Dopaminergic denervation in patients with Parkinson's disease is associated with changes in brain metabolism. Cerebral in-vivo mapping of glucose metabolism has been studied in severe stable parkinsonian monkeys, but data on brain metabolic changes in early stages of dopaminergic depletion of this model is lacking. Here, we report cerebral metabolic changes associated with progressive nigrostriatal lesion in the pre-symptomatic and symptomatic stages of the progressive 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) monkey model of Parkinson's Disease. Monkeys (Macaca fascicularis) received MPTP injections biweekly to induce progressive grades of dopamine depletion. Monkeys were sorted according to motor scale assessments in control, asymptomatic, recovered, mild, and severe parkinsonian groups. Dopaminergic depletion in the striatum and cerebral metabolic patterns across groups were studied in vivo by positron emission tomography (PET) using monoaminergic ([11C]-dihydrotetrabenazine; 11C-DTBZ) and metabolic (2-[18F]-fluoro-2-deoxy-d-glucose; 18F-FDG) radiotracers. 11C-DTBZ-PET analysis showed progressive decrease of binding potential values in the striatum of monkeys throughout MPTP administration and the development of parkinsonian signs. 18F-FDG analysis in asymptomatic and recovered animals showed significant hypometabolism in temporal and parietal areas of the cerebral cortex in association with moderate dopaminergic nigrostriatal depletion. Cortical hypometabolism extended to involve a larger area in mild parkinsonian monkeys, which also exhibited hypermetabolism in the globus pallidum pars interna and cerebellum. In severe parkinsonian monkeys, cortical hypometabolism extended further to lateral-frontal cortices and hypermetabolism also ensued in the thalamus and cerebellum. Unbiased histological quantification of neurons in Brodmann's area 7 in the parietal cortex did not reveal neuron loss in parkinsonian monkeys versus controls. Early dopaminergic nigrostriatal depletion is associated with cortical, mainly temporo-parietal hypometabolism unrelated to neuron loss. These findings, together with recent evidence from Parkinson's Disease patients, suggest that early cortical hypometabolism may be associated and driven by subcortical changes that need to be evaluated appropriately. Altogether, these findings could be relevant when potential disease modifying therapies become available.
Assuntos
Transtornos Parkinsonianos , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina , Animais , Córtex Cerebral/metabolismo , Corpo Estriado/metabolismo , Dopamina/metabolismo , Humanos , Transtornos Parkinsonianos/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Primatas/metabolismoRESUMO
BACKGROUND: Cardiac fibroblasts (CFs) have a central role in the ventricular remodeling process associated with different types of fibrosis. Recent studies have shown that fibroblasts do not respond homogeneously to heart injury. Because of the limited set of bona fide fibroblast markers, a proper characterization of fibroblast population heterogeneity in response to cardiac damage is lacking. The purpose of this study was to define CF heterogeneity during ventricular remodeling and the underlying mechanisms that regulate CF function. METHODS: Collagen1α1-GFP (green fluorescent protein)-positive CFs were characterized after myocardial infarction (MI) by single-cell and bulk RNA sequencing, assay for transposase-accessible chromatin sequencing, and functional assays. Swine and patient samples were studied using bulk RNA sequencing. RESULTS: We identified and characterized a unique CF subpopulation that emerges after MI in mice. These activated fibroblasts exhibit a clear profibrotic signature, express high levels of Cthrc1 (collagen triple helix repeat containing 1), and localize into the scar. Noncanonical transforming growth factor-ß signaling and different transcription factors including SOX9 are important regulators mediating their response to cardiac injury. Absence of CTHRC1 results in pronounced lethality attributable to ventricular rupture. A population of CFs with a similar transcriptome was identified in a swine model of MI and in heart tissue from patients with MI and dilated cardiomyopathy. CONCLUSIONS: We report CF heterogeneity and their dynamics during the course of MI and redefine the CFs that respond to cardiac injury and participate in myocardial remodeling. Our study identifies CTHRC1 as a novel regulator of the healing scar process and a target for future translational studies.
Assuntos
Proteínas da Matriz Extracelular/metabolismo , Fibroblastos/metabolismo , Infarto do Miocárdio/metabolismo , Miocárdio/metabolismo , RNA-Seq , Análise de Célula Única , Animais , Cardiomiopatia Dilatada/genética , Cardiomiopatia Dilatada/metabolismo , Cardiomiopatia Dilatada/patologia , Modelos Animais de Doenças , Proteínas da Matriz Extracelular/genética , Fibroblastos/patologia , Humanos , Camundongos , Infarto do Miocárdio/genética , Infarto do Miocárdio/patologia , Miocárdio/patologiaRESUMO
The success of cell therapy for the treatment of myocardial infarction depends on finding novel approaches that can substantially implement the engraftment of the transplanted cells. In order to enhance cell engraftment, most studies have focused on the pretreatment of transplantable cells. Here we have considered an alternative approach that involves the preconditioning of infarcted heart tissue to reduce endogenous cell activity and thus provide an advantage to our exogenous cells. This treatment is routinely used in other tissues such as bone marrow and skeletal muscle to improve cell engraftment, but it has never been taken in cardiac tissue. To avoid long-term cardiotoxicity induced by full heart irradiation we developed a rat model of a catheter-based heart irradiation system to locally impact a delimited region of the infarcted cardiac tissue. As proof of concept, we transferred ZsGreen+ iPSCs in the infarcted heart, due to their ease of use and detection. We found a very significant increase in cell engraftment in preirradiated rats. In this study, we demonstrate for the first time that preconditioning the infarcted cardiac tissue with local irradiation can substantially enhance cell engraftment.
Assuntos
Braquiterapia/métodos , Precondicionamento Isquêmico/métodos , Infarto do Miocárdio/terapia , Transplante de Células-Tronco/métodos , Animais , Células Cultivadas , Coração/efeitos da radiação , Células-Tronco Pluripotentes Induzidas/transplante , Masculino , Camundongos , Ratos , Ratos Sprague-DawleyRESUMO
Malignant hypertension is listed among the causes of secondary thrombotic microangiopathy, but pathogenic mutations in complement genes have been reported in patients with hypertension-induced thrombotic microangiopathy. Here we investigated the frequency and severity of hypertension in 55 patients with primary atypical hemolytic uremic syndrome (aHUS). A genetic analysis was performed in all patients, and funduscopic examination was performed in all the patients with Grades 2 and 3 hypertension. A cohort of 110 patients with malignant hypertension caused by diseases other than aHUS served as control. Thirty-six patients with aHUS presented Grade 2 or Grade 3 hypertension and funduscopic examination showed malignant hypertension in 19. Genetic abnormalities in complement were found in 19 patients (37% among patients with malignant hypertension). Plasmapheresis was performed in 46 patients and 26 received eculizumab. Renal and hematological responses were significantly lower after plasmapheresis (24%) than after eculizumab (81%). Renal survival was significantly higher in patients treated with eculizumab (85% at one, three and five years) compared to patients who did not receive this treatment (54%, 46% and 41%), respectively. Response to eculizumab was independent of hypertension severity and the presence of complement genetic abnormalities. Among patients with malignant hypertension caused by other diseases the prevalence of thrombotic microangiopathy was very low (5%). Thus, severe and malignant hypertension are common among patients with aHUS and eculizumab treatment leads to a higher renal survival when compared to plasmapheresis. However, thrombotic microangiopathy is uncommon among patients presenting with malignant hypertension caused by diseases other than aHUS.
Assuntos
Síndrome Hemolítico-Urêmica Atípica/complicações , Proteínas do Sistema Complemento/genética , Hipertensão Maligna/epidemiologia , Índice de Gravidade de Doença , Adulto , Anticorpos Monoclonais Humanizados/uso terapêutico , Síndrome Hemolítico-Urêmica Atípica/genética , Síndrome Hemolítico-Urêmica Atípica/terapia , Inativadores do Complemento/uso terapêutico , Feminino , Humanos , Hipertensão Maligna/diagnóstico , Hipertensão Maligna/genética , Hipertensão Maligna/terapia , Incidência , Masculino , Pessoa de Meia-Idade , Plasmaferese , Estudos Retrospectivos , Adulto JovemRESUMO
Gliomatosis cerebri is a diffuse infiltrating glioma of neuroepithelial origin that affects more than 2 cerebral lobes. This is rarely seen in pediatric patients. The clinical presentation and imaging are very unspecific, and a biopsy is typically needed for the diagnosis. Given the widespread nature of the disease, surgical treatment is not possible and has a poor overall prognosis. A pediatric patient presented with elevated intracranial pressure. All initial studies were negative, and the imaging showed a symmetrical affection involving the supratentorial and infratentorial regions. A biopsy ultimately confirmed gliomatosis cerebri. This case describes a unique clinical presentation of gliomatosis cerebri in a pediatric patient.
Assuntos
Neoplasias Encefálicas/diagnóstico , Neoplasias Neuroepiteliomatosas/diagnóstico , Convulsões/etiologia , Adolescente , Encéfalo/patologia , Neoplasias Encefálicas/complicações , Diagnóstico Diferencial , Humanos , Hipertensão Intracraniana/etiologia , Imageamento por Ressonância Magnética , Masculino , Neoplasias Neuroepiteliomatosas/complicaçõesAssuntos
Alopecia em Áreas , Dermatite Alérgica de Contato , Tinturas para Cabelo , Tatuagem , Humanos , Tinturas para Cabelo/efeitos adversos , Dermatite Alérgica de Contato/diagnóstico , Dermatite Alérgica de Contato/etiologia , Alopecia em Áreas/etiologia , Testes do Emplastro , Fenilenodiaminas , CorantesRESUMO
Papular acantholytic dermatosis of the vulva is a rare, chronic disorder and is an entity that remains to be fully understood. It shares clinical and histopathological overlap with Darier disease and Hailey-Hailey disease. We describe a 30-year-old woman with papular acantholytic dermatosis of the vulva. The lesions consisted of whitish papules and erosions on the labia majora. Histologically, there was hyperkeratosis and focal parakeratosis with acantholytic and dyskeratotic cells. She did not respond completely to topical steroids but clinical improvement occurred after the use of topical tacrolimus.
Assuntos
Acantólise/tratamento farmacológico , Inibidores de Calcineurina/administração & dosagem , Tacrolimo/administração & dosagem , Doenças da Vulva/tratamento farmacológico , Acantólise/patologia , Administração Tópica , Adulto , Feminino , Humanos , Doenças da Vulva/patologiaRESUMO
Carbon-11 labeled dihydrotetrabenazine ((11)C-DTBZ) binds to the vesicular monoamine transporter 2 and has been used to assess nigro-striatal integrity in animal models and patients with Parkinson's disease. Here, we applied (11)C-DTBZ positron emission tomography (PET) to obtain longitudinally in-vivo assessment of striatal dopaminergic loss in the classic unilateral and in a novel bilateral 6-hydroxydopamine (6-OHDA) lesion rat model. Forty-four Sprague-Dawley rats were divided into 3 sub-groups: 1. 6-OHDA-induced unilateral lesion in the medial forebrain bundle, 2. bilateral lesion by injection of 6-OHDA in the third ventricle, and 3. vehicle injection in either site. (11)C-DTBZ PET studies were investigated in the same animals successively at baseline, 1, 3 and 6weeks after lesion using an anatomically standardized volumes-of-interest approach. Additionally, 12 rats had PET and Magnetic Resonance Imaging to construct a new (11)C-DTBZ PET template. Behavior was characterized by rotational, catalepsy and limb-use asymmetry tests and dopaminergic striatal denervation was validated post-mortem by immunostaining of the dopamine transporter (DAT). (11)C-DTBZ PET showed a significant decrease of striatal binding (SB) values one week after the unilateral lesion. At this point, there was a 60% reduction in SB in the affected hemisphere compared with baseline values in 6-OHDA unilaterally lesioned animals. A 46% symmetric reduction over baseline SB values was found in bilaterally lesioned rats at the first week after lesion. SB values remained constant in unilaterally lesioned rats whereas animals with bilateral lesions showed a modest (22%) increase in binding values at the 3rd and 6th weeks post-lesion. The degree of striatal dopaminergic denervation was corroborated histologically by DAT immunostaining. Statistical analysis revealed a high correlation between (11)C-DTBZ PET SB and striatal DAT immunostaining values (r=0.95, p<0.001). The data presented here indicate that (11)C-DTBZ PET may be used to ascertain changes occurring in-vivo throughout the evolution of nigro-striatal dopaminergic neurodegeneration, mainly in the unilateral 6-OHDA lesion rat.
Assuntos
Adrenérgicos/toxicidade , Lateralidade Funcional/fisiologia , Oxidopamina/toxicidade , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/etiologia , Animais , Apomorfina/farmacologia , Encéfalo/diagnóstico por imagem , Encéfalo/efeitos dos fármacos , Radioisótopos de Carbono/farmacocinética , Modelos Animais de Doenças , Agonistas de Dopamina , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Lateralidade Funcional/efeitos dos fármacos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons , Ligação Proteica/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Estatísticas não Paramétricas , Tetrabenazina/análogos & derivados , Tetrabenazina/farmacocinéticaRESUMO
Leiomyoma are slowly growing lesions arising from smooth muscle. Orbital location has been reported in 25 cases. Histological findings and no recurrence after total resection support their benign behaviour. We report an intraconal orbital haemangioleiomyoma in a 55-year-old female treated by total resection through fronto-orbital craniotomy, with no recurrence after 15 months of follow-up. Radiological and pathological features are discussed, emphasising the prognostic role of the surgery.
Assuntos
Hemangioma Cavernoso/cirurgia , Leiomioma/cirurgia , Neoplasias Orbitárias/cirurgia , Craniotomia , Exoftalmia/etiologia , Feminino , Seguimentos , Hemangioma Cavernoso/complicações , Hemangioma Cavernoso/diagnóstico por imagem , Hemangioma Cavernoso/patologia , Humanos , Leiomioma/complicações , Leiomioma/diagnóstico por imagem , Leiomioma/patologia , Pessoa de Meia-Idade , Neoplasias Orbitárias/complicações , Neoplasias Orbitárias/diagnóstico por imagem , Neoplasias Orbitárias/patologia , RadiografiaRESUMO
In recent years there has been an increasing interest in expanded hemodialysis (HDx), an emerging renal replacement therapy based on the use of medium cut-off membranes (MCO). Thanks to the internal architecture of these types of membranes, with a higher pore size and smaller fiber inner diameter to favor internal filtration rate, they can increase the removal of larger middle molecules in conventional hemodialysis. Secondarily, several reports suggest that this therapy potentially improve the outcomes for end-stage renal disease patients. However, HDx has not been defined yet and the characteristics of MCO membranes are not well stablished. The aim of this narrative review is to define HDx and summarize the dialyzers that have been used so far to perform this therapy, collect the evidence available on its efficacy and clinical outcomes compared with other hemodialysis techniques and settle the bases for its optimal prescription.
RESUMO
Generating organs from stem cells through blastocyst complementation is a promising approach to meet the clinical need for transplants. In order to generate rejection-free organs, complementation of both parenchymal and vascular cells must be achieved, as endothelial cells play a key role in graft rejection. Here, we used a lineage-specific cell ablation system to produce mouse embryos unable to form both the cardiac and vascular systems. By mouse intraspecies blastocyst complementation, we rescued heart and vascular system development separately and in combination, obtaining complemented hearts with cardiomyocytes and endothelial cells of exogenous origin. Complemented chimeras were viable and reached adult stage, showing normal cardiac function and no signs of histopathological defects in the heart. Furthermore, we implemented the cell ablation system for rat-to-mouse blastocyst complementation, obtaining xenogeneic hearts whose cardiomyocytes were completely of rat origin. These results represent an advance in the experimentation towards the in vivo generation of transplantable organs.
Assuntos
Sistema Cardiovascular , Coração , Células-Tronco Pluripotentes , Animais , Camundongos , Ratos , Blastocisto , Células Endoteliais , Miócitos Cardíacos , Coração/embriologia , Sistema Cardiovascular/embriologiaRESUMO
Despite the potential of CAR-T therapies for hematological malignancies, their efficacy in patients with relapse and refractory Acute Myeloid Leukemia has been limited. The aim of our study has been to develop and manufacture a CAR-T cell product that addresses some of the current limitations. We initially compared the phenotype of T cells from AML patients and healthy young and elderly controls. This analysis showed that T cells from AML patients displayed a predominantly effector phenotype, with increased expression of activation (CD69 and HLA-DR) and exhaustion markers (PD1 and LAG3), in contrast to the enriched memory phenotype observed in healthy donors. This differentiated and more exhausted phenotype was also observed, and corroborated by transcriptomic analyses, in CAR-T cells from AML patients engineered with an optimized CAR construct targeting CD33, resulting in a decreased in vivo antitumoral efficacy evaluated in xenograft AML models. To overcome some of these limitations we have combined CRISPR-based genome editing technologies with virus-free gene-transfer strategies using Sleeping Beauty transposons, to generate CAR-T cells depleted of HLA-I and TCR complexes (HLA-IKO/TCRKO CAR-T cells) for allogeneic approaches. Our optimized protocol allows one-step generation of edited CAR-T cells that show a similar phenotypic profile to non-edited CAR-T cells, with equivalent in vitro and in vivo antitumoral efficacy. Moreover, genomic analysis of edited CAR-T cells revealed a safe integration profile of the vector, with no preferences for specific genomic regions, with highly specific editing of the HLA-I and TCR, without significant off-target sites. Finally, the production of edited CAR-T cells at a larger scale allowed the generation and selection of enough HLA-IKO/TCRKO CAR-T cells that would be compatible with clinical applications. In summary, our results demonstrate that CAR-T cells from AML patients, although functional, present phenotypic and functional features that could compromise their antitumoral efficacy, compared to CAR-T cells from healthy donors. The combination of CRISPR technologies with transposon-based delivery strategies allows the generation of HLA-IKO/TCRKO CAR-T cells, compatible with allogeneic approaches, that would represent a promising option for AML treatment.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Animais , Humanos , Idoso , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/metabolismo , Linfócitos T/metabolismo , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/metabolismo , Imunoterapia Adotiva/métodos , Modelos Animais de DoençasRESUMO
Extracorporeal organ support in patients with dysfunction of vital organs like the kidney, heart, and liver has proven helpful in bridging the patients to recovery or more definitive therapy. Mechanical ventilation in patients with respiratory failure, although indispensable, has been associated with worsening injury to the lungs, termed ventilator-induced lung injury. Application of lung-protective ventilation strategies are limited by inevitable hypercapnia and hypercapnic acidosis. Various alternative extracorporeal strategies, proposed more than 30 years ago, to combat hypercapnia are now more readily available. In particular, the venovenous approach to effective carbon dioxide removal, which involves minimal invasiveness comparable to renal replacement therapy, appears to be very promising. The clinical applications of these extracorporeal carbon dioxide removal therapies may extend beyond just lung protection in ventilated patients. This article summarizes the rationale, technology and clinical application of various extracorporeal lung assist techniques available for clinical use, and some of the future perspectives in the field.
Assuntos
Dióxido de Carbono/sangue , Dióxido de Carbono/isolamento & purificação , Circulação Extracorpórea/métodos , Catéteres , Desenho de Equipamento , Circulação Extracorpórea/história , Circulação Extracorpórea/instrumentação , Oxigenação por Membrana Extracorpórea/história , Oxigenação por Membrana Extracorpórea/instrumentação , Oxigenação por Membrana Extracorpórea/métodos , História do Século XX , História do Século XXI , Humanos , Pulmão/patologia , Insuficiência Respiratória/terapiaRESUMO
UNLABELLED: Dopaminergic depletion in the nigrostriatal system is the neurochemical hallmark of Parkinson's disease (PD). Although numerous efforts have been made to determine the evolution of dopaminergic depletion in PD, "in vivo" data concerning the stages of this process are still scarce. We evaluated 6-[18F]-fluoro-l-DOPA ((18)F-DOPA) and 11C-(+)-alpha-dihydrotetrabenazine ((11)C-DTBZ) using PET in a model of chronically MPTP-induced parkinsonism in non-human primates. METHODS: Sixty-seven cynomolgus monkeys (Macacafascicularis) were included in the study. Progressive parkinsonism was induced by repeated administration of small doses of MPTP (iv) over several months. Animals were classified as controls, asymptomatic, recovered (having exhibited parkinsonian features transiently) and stable parkinsonian, according to their motor status. Analysis of striatal dopaminergic activity was conducted by regions of interest (ROI) and statistical parametric mapping (SPM) over normalized parametric images. RESULTS: A progressive loss of striatal uptake was evident among groups for both radiotracers, which correlated significantly with the clinical motor status. Changes occurred earlier, i.e. in the less affected stages, with (11)C-DTBZ. Similar results were achieved by ROI and SPM analysis. Uptake was similar with both radiotracers for the asymptomatic and recovered groups. CONCLUSIONS: Serial assessment with (18)F-DOPA and (11)C-DTBZ PETs provides an effective approach to evaluate evolution of dopaminergic depletion in monkeys with MPTP-induced parkinsonism. This approach could be useful to perform studies aiming to test the effect of early therapeutic intervention and putative neuroprotective treatments.
Assuntos
Corpo Estriado/metabolismo , Dopamina/metabolismo , Transtornos Parkinsonianos/metabolismo , Animais , Mapeamento Encefálico , Radioisótopos de Carbono , Núcleo Caudado/diagnóstico por imagem , Núcleo Caudado/metabolismo , Corpo Estriado/diagnóstico por imagem , Modelos Animais de Doenças , Progressão da Doença , Dopamina/análogos & derivados , Dopamina/deficiência , Discinesias/diagnóstico por imagem , Discinesias/metabolismo , Feminino , Macaca fascicularis , Masculino , Transtornos Parkinsonianos/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Putamen/diagnóstico por imagem , Putamen/metabolismo , Índice de Gravidade de Doença , Processamento de Sinais Assistido por Computador , Tetrabenazina/análogos & derivadosRESUMO
BACKGROUND: Although necrotizing pneumonia (NN) is one of the most feared complications of community-acquired pneumonia, data in pediatric patients are scarce. The objective of this article is to describe children admitted to pediatric intensive care unit (PICU) because of NN. METHODS: Retrospective-prospective observational study in children admitted with NN to PICU (from January 1, 2010, to December 31, 2018). The data collected included information on disease epidemiology, PICU management, respiratory assistance and disease evolution. RESULTS: Fifty-one children were included, 42 of 51 had received 7-valent or 13-valent pneumococcal vaccine. Median age was 3.2 years (1.9-4.2), 15 of 51 had signs of sepsis at admission. Forty-nine patients presented pleural effusion with drainage in 46. The most common respiratory support modality was high-flow oxygen nasal cannula (17/51). Computed tomography was the gold standard for diagnosis. Etiologic diagnosis was obtained in 34 of 51, and pneumococcus was isolated in 29 of 34. In all of these cases, initial detection was made by capsular antigen in pleural fluid. Children with pneumococcal NN had fewer days of evolution prior to PICU admission (P = 0.041). Cefotaxime with clindamycin was used in 49 of 51. Surgery was necessary in 3 of 51 patients. After PICU discharge, only 5 of 51 were readmitted. There were deaths. CONCLUSIONS: In our study, the NN was mainly observed in children around 3 years old. The main causal agent was pneumococcus. The evolution towards NN appeared to be faster than in case of other etiologies. Surgery management was unusual. All children required prolonged admissions but had a full clinical recovery.
Assuntos
Infecções Comunitárias Adquiridas/complicações , Hospitalização/estatística & dados numéricos , Unidades de Terapia Intensiva Pediátrica/estatística & dados numéricos , Pneumonia Necrosante/diagnóstico , Pneumonia Necrosante/epidemiologia , Antibacterianos/uso terapêutico , Pré-Escolar , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/microbiologia , Infecções Comunitárias Adquiridas/mortalidade , Feminino , Humanos , Lactente , Masculino , Vacinas Pneumocócicas/administração & dosagem , Pneumonia Necrosante/microbiologia , Estudos Prospectivos , Estudos Retrospectivos , Streptococcus pneumoniae/isolamento & purificaçãoRESUMO
Samples from 13 beaches along the northern Spanish coast, a region with a history of heavy industries, were first screened to identify signs of pollution. High concentrations of Hg and Ba on Vega beach were found, both elements belong to the fluorite ore paragenesis, mined in the surroundings. Samples of beach and fluvial sediments, and nearby soils were collected in Vega beach area to address potential Hg pollution, fate and sources. Most samples showed a similar pollutants fingerprint to that of beach samples, especially those taken from white dunes, registering notable Hg concentrations. Hg was enriched in the finer fractions, and overall the main input was attributed to the mining waste discharged along the coast in the past. Although a specific risk assessment and study of the submerged sediments are advisable for this area, Hg bioavailability and methylation were low, thus indicating that this metal poses a reduced environmental risk.
Assuntos
Mercúrio/análise , Mineração , Poluentes do Solo/análise , Poluentes Químicos da Água/análise , Bário/análise , Praias , Disponibilidade Biológica , Monitoramento Ambiental , Sedimentos Geológicos/análise , Mercúrio/farmacocinética , Metais/análise , Poluentes do Solo/farmacocinética , Espanha , Poluentes Químicos da Água/farmacocinéticaRESUMO
In the treatment of bone non-unions, an alternative to bone autografts is the use of bone morphogenetic proteins (BMPs), e.g., BMP-2, BMP-7, with powerful osteoinductive and osteogenic properties. In clinical settings, these osteogenic factors are applied using absorbable collagen sponges for local controlled delivery. Major side effects of this strategy are derived from the supraphysiological doses of BMPs needed, which may induce ectopic bone formation, chronic inflammation, and excessive bone resorption. In order to increase the efficiency of the delivered BMPs, we designed cryostructured collagen scaffolds functionalized with hydroxyapatite, mimicking the structure of cortical bone (aligned porosity, anisotropic) or trabecular bone (random distributed porosity, isotropic). We hypothesize that an anisotropic structure would enhance the osteoconductive properties of the scaffolds by increasing the regenerative performance of the provided rhBMP-2. In vitro, both scaffolds presented similar mechanical properties, rhBMP-2 retention and delivery capacity, as well as scaffold degradation time. In vivo, anisotropic scaffolds demonstrated better bone regeneration capabilities in a rat femoral critical-size defect model by increasing the defect bridging. In conclusion, anisotropic cryostructured collagen scaffolds improve bone regeneration by increasing the efficiency of rhBMP-2 mediated bone healing.
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Islet-1 (Isl1) is a transcription factor essential for life expressed in specific cells with different developmental origins. We have generated iPSC lines from fibroblasts of the transgenic Ai6 x Isl1-Cre (Ai6IslCre) mouse. Here we describe the complete characterization of four iPSC lines: ATCi-Ai6IslCre10, ATCi-Ai6IslCre35, ATCi-Ai6IslCre74 and ATCi-Ai6IslCre80.
Assuntos
Proteínas com Homeodomínio LIM/genética , Fatores de Transcrição/genética , Animais , Diferenciação Celular , Fibroblastos/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , CamundongosRESUMO
Meningococcal infection associates high morbidity and mortality. Viral coinfection has been described mainly with herpes and respiratory virus. We describe a child who suffered a tonic-clonic seizure with hypotension, tachycardia and low Glasgow Coma Scale. She maintained an altered mental status and required hemodynamic stabilization in the Pediatric Intensive Care Unit. Wide spectrum antibiotherapy was initiated. She suffered large and foul-smelling liquid not bloody stools which were cultured and studied by polymerase chain reaction. The cerebrospinal fluid was normal. Later the polymerase chain reaction stools were positive to astrovirus, and the blood polymerase chain reaction was positive to Neisseria meningitidis group B. As far as we know, this is the first case of astrovirus and Neisseria meningitidis coinfection described in children. This virus should be considered as new cause of viral coinfection to discard if unexplained abdominal pain or vomits and liquid stools are observed.
La infección meningocócica tiene una elevada morbimortalidad. Las coinfecciones virales han sido descritas, fundamentalmente, por virus herpes y respiratorios. Se presenta una paciente que ingresó al Servicio de Emergencia con convulsión tónico-clónica, hipotensión, taquicardia y escala de Glasgow posterior baja. En la Unidad de Cuidados Intensivos mantuvo alteración del nivel de conciencia y requirió estabilización hemodinámica. Se inició antibioterapia de amplio espectro. La paciente mostró deposiciones líquidas malolientes, sin sangre, que fueron cultivadas y estudiadas mediante reacción en cadena de la polimerasa. El líquido cefalorraquídeo fue normal. Las deposiciones resultaron positivas para astrovirus. Se confirmó, mediante reacción en cadena de la polimerasa en sangre, la presencia de Neisseria meningitidis serogrupo B. Se presenta el primer caso pediátrico de coinfección por astrovirus y Neisseria meningitidis. Este virus debería incluirse entre las causas de coinfección para descartar en caso de clínica abdominal predominante, vómitos o deposiciones líquidas.