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1.
J Org Chem ; 89(3): 1438-1445, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38241605

RESUMO

A broad survey of heterogeneous hydrogenation catalysts has been conducted for the reduction of heterocycles commonly found in pharmaceuticals. The comparative reactivity of these substrates is reported as a function of catalyst, temperature, and hydrogen pressure. This analysis provided several catalysts with complementary reactivity between substrates. We then explored a series of bisheterocyclic substrates that provided an intramolecular competition of heterocycle hydrogenation reactivity. In several cases, complete selectivity could be achieved for reduction of one heterocycle and isolated yields are reported. A general trend in reactivity is inferred in which quinoline is the most reactive, followed by pyrazine, then pyrrole and with pyridine being the least reactive.

2.
J Endocrinol Invest ; 47(11): 2775-2784, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38556572

RESUMO

PURPOSE: Gorham-Stout disease is a very rare disorder characterized by progressive bone erosion and angiomatous proliferation; its etiopathogenesis is still unknown, and diagnosis is still performed by exclusion criteria. The alteration of bone remodeling activity has been reported in patients; in this study, we characterized circulating osteoclast and osteogenic precursors that could be important to better understand the osteolysis observed in patients. METHODS: Flow cytometry analysis of PBMC (Peripheral Blood Mononuclear Cells) was performed to characterize circulating osteoclast and osteogenic precursors in GSD patients (n = 9) compared to healthy donors (n = 55). Moreover, ELISA assays were assessed to evaluate serum levels of bone markers including RANK-L (Receptor activator of NF-κB ligand), OPG (Osteoprotegerin), BALP (Bone Alkaline Phosphatase) and OCN (Osteocalcin). RESULTS: We found an increase of CD16-/CD14+CD11b+ and CD115+/CD14+CD11b+ osteoclast precursors in GSD patients, with high levels of serum RANK-L that could reflect the increase of bone resorption activity observed in patients. Moreover, no significant alterations were found regarding osteogenic precursors and serum levels of BALP and OCN. CONCLUSION: The analysis of circulating bone cell precursors, as well as of RANK-L, could be relevant as an additional diagnostic tool for these patients and could be exploited for therapeutic purposes.


Assuntos
Osteoclastos , Osteogênese , Osteólise Essencial , Humanos , Masculino , Feminino , Osteoclastos/metabolismo , Osteoclastos/patologia , Adulto , Osteogênese/fisiologia , Osteólise Essencial/patologia , Osteólise Essencial/sangue , Osteólise Essencial/diagnóstico , Biomarcadores/sangue , Adolescente , Estudos de Casos e Controles , Pessoa de Meia-Idade , Adulto Jovem , Criança , Leucócitos Mononucleares/metabolismo , Citometria de Fluxo/métodos , Fosfatase Alcalina/sangue
3.
J Public Health Manag Pract ; 30(1): 122-129, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37678261

RESUMO

CONTEXT: In response to the first reported mpox cases in May 2022, the US government implemented plans to bring testing, treatment, and vaccines to communities disproportionately affected by mpox-including the population of men who have sex with men (MSM) and Black/African American and Hispanic/Latino men, 2 subpopulations experiencing vaccination disparities. We describe the development and implementation of the US Mpox Vaccine Equity Pilot Program (MVEPP), characteristics of completed vaccination projects, and challenges that occurred. We also discuss opportunities for reducing vaccination disparities in future outbreaks. PROGRAM: To address reported vaccination disparities, the US government launched MVEPP in 2 phases. Phase 1 centered around public events attended by large numbers of gay, bisexual, and other MSM, such as Pride festivals. Phase 2 asked health departments to propose mpox vaccination projects specifically aimed at reducing or eliminating racial/ethnic and other demographic disparities in mpox vaccination. IMPLEMENTATION: MVEPP received 35 vaccination project proposals. We analyzed data from 22 completed projects that resulted in 25 675 doses of JYNNEOS administered. We note 3 innovative strategies that were implemented in several projects: direct collaboration with organizations providing services to MSM and transgender women; implementation of MVEPP projects in unique nonclinical community settings and at venues frequented by MSM and transgender women; and offering an array of services as part of mpox vaccination projects, rather than offering only mpox vaccination. EVALUATION: MVEPP highlighted the importance of recognizing and working to eliminate racial/ethnic and other disparities in access to medical countermeasures during a public health emergency. Jurisdictions developed and implemented innovative strategies to bring mpox vaccination and related services to communities disproportionately affected by mpox-including MSM and the subpopulations of Black/African American and Hispanic/Latino MSM. Lessons learned from MVEPP may inform efforts to reduce disparities during future public health responses.


Assuntos
Disparidades em Assistência à Saúde , Mpox , Minorias Sexuais e de Gênero , Vacina Antivariólica , Vacinação , Feminino , Humanos , Masculino , Hispânico ou Latino , Homossexualidade Masculina , Mpox/prevenção & controle , Projetos Piloto , Vacina Antivariólica/uso terapêutico , Disparidades em Assistência à Saúde/etnologia , Disparidades em Assistência à Saúde/estatística & dados numéricos , Negro ou Afro-Americano
4.
J Public Health Manag Pract ; 29(1): 56-63, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36448760

RESUMO

CONTEXT: The Centers for Disease Control and Prevention (CDC) developed a workforce training on sexual and gender minorities (SGMs). OBJECTIVE: This article describes the evaluation of the training. DESIGN: Participants completed pre- and posttest surveys. After the pilot evaluation, some improvements were made to the curriculum and to the pre- and posttest questionnaires. Participants in subsequent (implementation) training were similarly asked to complete pre- and posttest questionnaires. SETTING: CDC. PARTICIPANTS: CDC staff. MAIN OUTCOME MEASURES: Participants' knowledge, ally identity, and perceptions of SGMs. RESULTS: Pilot and implementation training data showed increases in participant knowledge of 44% and 49%, respectively, increases in ally identity of 11% and 14%, respectively, and increases in positive perceptions of SGM of 25% and 31%, respectively. CONCLUSION: These results suggest that the CDC Ally Training may be a useful tool for improving staff knowledge and perceptions of SGM people.


Assuntos
Diversidade Cultural , Minorias Sexuais e de Gênero , Estados Unidos , Humanos , Comportamento Sexual , Centers for Disease Control and Prevention, U.S. , Currículo
5.
Rev Esp Enferm Dig ; 111(6): 431-436, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31021170

RESUMO

BACKGROUND: therapeutic monitoring of anti-TNF drugs and anti-drug antibody levels are useful for clinical decision-making, via the rationalization and optimization of the use of anti-TNF treatments. The objective of the present study was to validate the model of Ternant et al., in a cohort of patients with inflammatory bowel diseases (IBD). This model was originally established for patients with rheumatoid arthritis and was used in this study to optimize the adalimumab (ADA) dose and predict ADA trough levels (ATL). METHODS: this study used concentration data points from 30 IBD patients who received ADA treatment between 2014 and 2015. A goodness-of-fit of the model was determined by evaluating the relationship between the observed ATL values and population model-predicted values (PRED) or individual model-predicted values (IPRED). RESULTS: a total of 51 ADA concentration points were analyzed. The bias of the model was 2.39 (95% CI, 1.63-3.15) for PRED and 0.63 (95% CI, 0.23-1.03) for IPRED. The precision was 3.57 (95% CI, 2.90-4.13) and 1.53 (95% CI, 1.22-1.80), respectively. CONCLUSIONS: therapeutic drug monitoring involving ATL may allow the optimization of the treatment of IBD patients. The validation results of the phamacokinectic (PK) model for ADA in IBD patients are inadequate. However, additional studies will strengthen the bias and precision of the model.


Assuntos
Adalimumab/farmacocinética , Adalimumab/uso terapêutico , Anti-Inflamatórios/farmacocinética , Anti-Inflamatórios/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Modelos Químicos , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
6.
J Biol Regul Homeost Agents ; 30(4): 997-1007, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28078845

RESUMO

Photobiomodulation (PBM) can induce a set of different biological modulators either in vitro or in vivo. Experimental evidence has highlighted the role of light effects on the mechanisms related to inflammation, apoptosis and autophagy. The goal of this project was the evaluation of PBM on U937, an established cell line of histiocytic lymphoma origin. Several aspects of modulation of proinflammatory pathways were analyzed and autophagic and proapoptotic mechanisms related to low laser light exposure of cells were studied. As a source of low energy light emission, we used an NIR-LED device, characterized by an 880 nm-wavelength as light source. Flow cytometry analysis was performed on supernatants of controls and treated U937 cells to detect inflammatory cytokine levels. In order to evaluate NF-kB and caspase3 expressions, Western blot analysis was performed according to standard procedures. In this report, we show the effect of PBM on a monocyte/macrophage established tumor cell line (U-937). We demonstrate that LED exposure, in the presence or absence of lipopolysaccharide (LPS), activates cell degranulation, increased expression of Interleukin-8 (IL-8) and modulation of beta galactosidase activity. Evidence shows that the well-known pro-inflammatory nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) and the apoptotic marker (caspase3/cleaved-caspase3 ratio) are up-regulated in response to a proinflammatory biochemical pathway.


Assuntos
Apoptose/efeitos da radiação , Degranulação Celular/efeitos da radiação , Terapia com Luz de Baixa Intensidade , Macrófagos/efeitos da radiação , Monócitos/efeitos da radiação , Western Blotting , Caspase 3/metabolismo , Citometria de Fluxo , Humanos , Inflamação/metabolismo , Interleucina-8/metabolismo , Macrófagos/metabolismo , Monócitos/metabolismo , NF-kappa B/metabolismo , Células U937
7.
Adv Sci (Weinh) ; 11(18): e2306901, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38447155

RESUMO

Eggs and embryo manipulation is an important biotechnological challenge to enable positioning, entrapment, and selection of reproductive cells to advance into a new era of nature-like assisted reproductive technologies. Oviductin (OVGP1) is an abundant protein in the oviduct that binds reversibly to the zona pellucida, an extracellular matrix that surrounds eggs and embryos. Here, the study reports a new method coupling OVGP1 to magnetic nanoparticles (NP) forming a complex (NPOv). NPOv specifically surrounds eggs and embryos in a reversible manner. Eggs/embryos bound to NPOv can be moved or retained when subjected to a magnetic force, and interestingly only mature-competent eggs are attracted. This procedure is compatible with normal development following gametes function, in vitro fertilization, embryo development and resulting in the birth of healthy offspring. The results provide in vitro proof-of-concept that eggs and embryos can be precisely guided in the absence of physical contact by the use of magnets.


Assuntos
Zona Pelúcida , Zona Pelúcida/metabolismo , Animais , Feminino , Camundongos , Nanopartículas/química , Embrião de Mamíferos , Fertilização in vitro/métodos , Óvulo , Desenvolvimento Embrionário/fisiologia , Técnicas de Reprodução Assistida
8.
Microorganisms ; 11(8)2023 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-37630486

RESUMO

Quinoa (Chenopodium quinoa) is a highly nutritious crop that is resistant to adverse conditions. Due to the considerable increase in its commercial production in Andean soils, the plant is suffering the negative effects of monocropping, which reduces its yield. We used for the first time a high-throughput Illumina MiSeq sequencing approach to explore the composition, diversity, and functions of fungal and bacterial communities of the bulk and rhizosphere in soils of native C. quinoa affected by monocropping in the central Andes of Peru. The results showed that the bacterial and fungal community structure among the treatments was significantly changed by the monocropping and the types of soil (rhizosphere and bulk). Also, in soils subjected to monocropping, there was an increase in Actinobacteria and a decrease in Proteobacteria, and the reduction in the presence of Ascomycota and the increase in Basidiomycota. By alpha-diversity indices, lower values of bacteria and fungi were observed in the monoculture option compared to the soil not affected by monocropping, and sometimes significant differences were found between both. We detected differentially abundant phytopathogenic fungi and bacteria with growth-stimulating effects on plants. Also, we denoted a decrease in the abundance of the functional predictions in bacteria in the monocropped soils. This research will serve as a starting point to explore the importance and effects of microorganisms in degraded soils and their impact on the growth and quality of quinoa crops.

9.
Cir Cir ; 90(1): 120-123, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35120098

RESUMO

Cecal appendix tumors are extremely rare (less than 0.5%), with carcinoid tumors being described as the most common type of appendix tumor. A case of a 32-year-old male patient is reported, with no significant pathological history, with acute abdomen data. Laparoscopic appendectomy was decided, presenting findings of an appendicular inflammatory process, resulting in a neuroendocrine tumor histopathology report. Despite the fact that appendix neoplasias are rare, appendicitis is a common presentation, hence the importance of conducting histopathology studies on every piece of cecal appendix obtained.


Los tumores de apéndice cecal son extremadamente raros (menos del 0.5%), y los tumores carcinoides se describen como el tipo de tumor apendicular más frecuente. Se reporta el caso de un paciente de 32 años, sin antecedentes patológicos de importancia, con datos de abdomen agudo. Se decidió apendicectomía laparoscópica, presentando hallazgos de proceso inflamatorio apendicular, con reporte de histopatología de tumor neuroendocrino. Pese a que las neoplasias de apéndice son raras, la apendicitis es una presentación común, y de ahí la importancia de realizar estudios histopatológicos de toda pieza de apéndice cecal obtenida.


Assuntos
Neoplasias do Apêndice , Apendicite , Apêndice , Tumor Carcinoide , Laparoscopia , Adulto , Apendicectomia , Neoplasias do Apêndice/cirurgia , Apendicite/cirurgia , Apêndice/cirurgia , Tumor Carcinoide/cirurgia , Humanos , Masculino
10.
J Behav Health Serv Res ; 49(4): 470-486, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35618881

RESUMO

The COVID-19 pandemic caused disruptions in behavioral health services (BHS), essential for people experiencing homelessness (PEH). BHS changes created barriers to care and opportunities for innovative strategies for reaching PEH. The authors conducted 50 qualitative interviews with behavioral health providers in the USA during August-October 2020 to explore their observations of BHS changes for PEH. Interviews were transcribed and entered into MAXQDA for analysis and to identify salient themes. The largest impact from COVID-19 was the closure or limited hours for BHS and homeless shelters due to mandated "stay-at-home" orders or staff working remotely leading to a disconnection in services and housing linkages. Most providers initiated telehealth services for clients, yielding positive outcomes. Implications for BHS are the need for long-term strategies, such as advances in communication technology to support BHS and homeless services and to ensure the needs of underserved populations are met during public health emergencies.


Assuntos
COVID-19 , Pessoas Mal Alojadas , Habitação , Humanos , Pandemias , Saúde Pública
11.
Curr Opin Oncol ; 23(6): 617-23, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21825989

RESUMO

PURPOSE OF REVIEW: To highlight the most recent advances in PET imaging of brain tumors, aiming at expanding the referring physician's knowledge in the field, the sine qua non for translating PET into the practice of neuro-oncology. RECENT FINDINGS: The role of PET with amino acid tracers in the setting of brain lesions of unknown significance has been better defined, reducing the need for invasive procedures. The impact of PET-guided resection of high-grade glioma using ¹¹C-methionine (¹¹C-MET) has been strongly documented. [¹8F]Fluoroethyl-L-tyrosine is currently available for glioma management; advances in targeting glial tumor biopsy and monitoring response to standard chemoradiation of malignant glioma have been remarkable. 2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-penta-fluoropropyl)-acetamide is a rationally designed radiotracer with potential for imaging hypoxia in glioblastoma. New insights regarding the predictive value of 3-deoxy-3-[¹8F]fluorothymidine in outcome of recurrent malignant glioma treated with bevacizumab/irinotecan have been provided. First steps are being made toward apoptosis PET imaging for early assessment of radiotherapy response in brain metastases. SUMMARY: The use of ¹¹C-MET and ¹8F-labeled PET tracers is getting a more precise position in the management of brain tumors. Advances hold promises in routine decision-making and in the design and conduct of clinical trials.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Compostos Radiofarmacêuticos , Radioisótopos de Carbono , Didesoxinucleosídeos , Radioisótopos de Flúor , Glioblastoma/diagnóstico por imagem , Glioma/diagnóstico por imagem , Humanos , Metionina , Nitroimidazóis , Tomografia por Emissão de Pósitrons/métodos , Tomografia por Emissão de Pósitrons/tendências , Radiografia
12.
Cir Cir ; 89(5): 674-678, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34665176

RESUMO

BACKGROUND: Simultaneous ventral hernia repair with another intestinal surgery have been described. CASE REPORT: A case of complex ventral hernia in a patient with colostomy status is described. Infiltration of botulinic toxin and progressive preoperative pneumoperitoneum was performed successfully prior to the surgical procedure during which mechanic restitution of gastrointestinal and ventral hernioplasty. CONCLUSIONS: In selected patients, complex ventral hernia repair, with prior progressive preoperative pneumoperitoneum, and restitution of gastrointestinal tract can be done in a single surgical procedure, considering the patient's clinical conditions and the surgeon's experience.


ANTECEDENTES: Se ha descrito la reparación de hernias ventrales y alguna otra cirugía intestinal de manera simultánea. CASO CLÍNICO: Se describe el caso de una hernia ventral compleja con pérdida de dominio, en un paciente masculino en estatus de colostomía. Se realizó infiltración de toxina botulínica más neumoperitoneo progresivo preoperatorio previo al acto quirúrgico, durante el cual se realizó restitución mecánica del tránsito intestinal y hernioplastia ventral exitosamente. CONCLUSIONES: En pacientes seleccionados, la reparación de la hernia ventral compleja, previo manejo con neumoperitoneo preoperatorio y restitución del tránsito intestinal, puede realizarse en un solo procedimiento quirúrgico, considerando las condiciones clínicas del paciente y la experiencia del cirujano.


Assuntos
Parede Abdominal , Hérnia Ventral , Parede Abdominal/cirurgia , Anastomose Cirúrgica , Colostomia , Hérnia Ventral/cirurgia , Herniorrafia , Humanos , Telas Cirúrgicas
13.
Mol Cell Endocrinol ; 509: 110802, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32259636

RESUMO

Continuously elevated levels of growth hormone (GH) during life in mice are associated with hepatomegaly due to hepatocytes hypertrophy and hyperplasia, chronic liver inflammation, elevated levels of arachidonic acid (AA) at young ages and liver tumors development at old ages. In this work, the hepatic expression of enzymes involved in AA metabolism, cPLA2α, COX1 and COX2 enzymes, was evaluated in young and old GH-transgenic mice. Mice overexpressing GH exhibited higher hepatic expression of cPLA2α, COX1 and COX2 in comparison to controls at young and old ages and in both sexes. In old mice, when tumoral and non-tumoral tissue were compared, elevated expression of COX2 was observed in tumors. In contrast, exposure to continuous lower levels of hormone for a short period affected COX1 expression only in males. Considering the role of inflammation during liver tumorigenesis, these findings support a role of alterations in AA metabolism in GH-driven liver tumorigenesis.


Assuntos
Fosfolipases A2 do Grupo IV/genética , Hormônio do Crescimento/metabolismo , Fígado/metabolismo , Prostaglandina-Endoperóxido Sintases/genética , Regulação para Cima/genética , Alanina Transaminase/sangue , Animais , Peso Corporal , Bovinos , Proliferação de Células , Feminino , Fosfolipases A2 do Grupo IV/metabolismo , Hepatócitos/citologia , Fígado/anatomia & histologia , Masculino , Camundongos Transgênicos , Tamanho do Órgão , Fosforilação , Prostaglandina-Endoperóxido Sintases/metabolismo , Ratos , Receptor IGF Tipo 1/metabolismo , Receptores da Somatotropina/metabolismo
14.
Front Microbiol ; 9: 484, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29662471

RESUMO

The bacterial endophytic communities residing within roots of maize (Zea mays L.) plants cultivated by a sustainable management in soils from the Quechua maize belt (Peruvian Andes) were examined using tags pyrosequencing spanning the V4 and V5 hypervariable regions of the 16S rRNA. Across four replicate libraries, two corresponding to sequences of endophytic bacteria from long time maize-cultivated soils and the other two obtained from fallow soils, 793 bacterial sequences were found that grouped into 188 bacterial operational taxonomic units (OTUs, 97% genetic similarity). The numbers of OTUs in the libraries from the maize-cultivated soils were significantly higher than those found in the libraries from fallow soils. A mean of 30 genera were found in the fallow soil libraries and 47 were in those from the maize-cultivated soils. Both alpha and beta diversity indexes showed clear differences between bacterial endophytic populations from plants with different soil cultivation history and that the soils cultivated for long time requires a higher diversity of endophytes. The number of sequences corresponding to main genera Sphingomonas, Herbaspirillum, Bradyrhizobium and Methylophilus in the maize-cultivated libraries were statistically more abundant than those from the fallow soils. Sequences of genera Dyella and Sreptococcus were significantly more abundant in the libraries from the fallow soils. Relative abundance of genera Burkholderia, candidatus Glomeribacter, Staphylococcus, Variovorax, Bacillus and Chitinophaga were similar among libraries. A canonical correspondence analysis of the relative abundance of the main genera showed that the four libraries distributed in two clearly separated groups. Our results suggest that cultivation history is an important driver of endophytic colonization of maize and that after a long time of cultivation of the soil the maize plants need to increase the richness of the bacterial endophytes communities.

15.
J Hosp Infect ; 100(3): 257-264, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30071264

RESUMO

BACKGROUND: Antibiotic resistance will cause about 10 million deaths per year by 2050. Fighting antimicrobial resistance is a health priority. Interventions aimed to reduce antimicrobial resistance, such as antibiotic stewardship programmes (ASPs), must be implemented. To be effective, those interventions, and the implementation process, should be matched with social-cultural context. The complexity of ASPs can no longer be developed without considering both organizational and information systems. AIM: To support ASPs through the co-design and implementation, in collaboration with healthcare workers, of a surveillance and clinical decision-support system to monitor antibiotic resistance and improve antibiotic prescription. METHODS: The surveillance and clinical decision-support system was designed and implemented in three Portuguese hospitals, using a participatory approach between researchers and healthcare workers following the Design Science Research Methodology. FINDINGS: Based on healthcare workers' requirements, we developed HAITooL, a real-time surveillance and clinical decision-support system that integrates visualizations of patient, microbiology, and pharmacy data, facilitating clinical decision. HAITooL monitors antibiotic usage and rates of antibiotic-resistant bacteria, allowing early identification of outbreaks. It is a clinical decision-support tool that integrates evidence-based algorithms to support proper antibiotic prescription. HAITooL was considered valuable to support monitoring of antibiotic resistant infections and an important tool for ASP sustainability. CONCLUSION: ASP implementation can be leveraged through a surveillance and clinical decision-support system such as HAITooL that allows antibiotic resistance monitoring and supports antibiotic prescription, once it has been adapted to the context and specific needs of healthcare workers and hospitals.


Assuntos
Antibacterianos/uso terapêutico , Gestão de Antimicrobianos , Infecções Bacterianas/tratamento farmacológico , Infecção Hospitalar/tratamento farmacológico , Sistemas de Apoio a Decisões Clínicas , Monitoramento Epidemiológico , Infecções Bacterianas/epidemiologia , Infecção Hospitalar/epidemiologia , Hospitais , Humanos , Portugal , Inquéritos e Questionários
16.
Oncotarget ; 9(11): 10175-10183, 2018 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-29515801

RESUMO

BACKGROUND: Response to targeting and non-targeting agents is variable and molecular information remains poorly described in patients with recurrent sonic-hedgehog-driven medulloblastoma (SHH-MB). MATERIALS AND METHODS: Clinical and PET/CT findings during treatment with successive hedgehog antagonists and temozolomide monotherapies are described in a heavily pre-treated patient with recurrent extraneural metastases from PTCH1 mutated/ wild type smoothened (SMO) CNS SHH-MB. Molecular tests were prospectively performed in tissue from two extraneural sites at progression. RESULTS: Sustained clinical/metabolic response was obtained to vismodegib. At progression, itraconazole was ineffective, but salvage temozolomide treatment results in a response similar to vismodegib. At further progression, acquired SMO and PIK3CA mutations were identified in bone (G477L and H1047A, respectively) and epidural (L412P and H1065L, respectively) metastases. No response was observed with subsequent sonidegib treatment. CONCLUSIONS: This is the first clinical report of recurrent extraneural PTCH1 mutated SHH-MB exhibiting: 1) a sustained response to vismodegib and temozolomide, and 2) inter-metastatic molecular heterogeneity and acquired SMO-G477L, SMO-L412P, and PIK3CA-H1065L mutations at progression, highlighting the need for a multitarget treatment approach.

17.
Rev Neurol ; 65(7): 289-294, 2017 Oct 01.
Artigo em Espanhol | MEDLINE | ID: mdl-28929470

RESUMO

INTRODUCTION: Sleep disorders are highly prevalent among the general population, although very few cases of sleep apnoea-hypopnoea syndrome (SAHS) have been reported in patients with narcolepsy. This study reviews the sleep disorders found in patients with narcolepsy, the prevalence of SAHS associated with these patients and their response to the different treatments. PATIENTS AND METHODS: We conducted an observation-based retrospective descriptive analysis of 25 patients diagnosed with narcolepsy, who were treated in our centre between October 2012 and December 2016. RESULTS: Of 470 patients evaluated in the specialised neurology consultation unit, 25 patients were diagnosed with narcolepsy (5.31%); 65% were males and the remaining 35% were females; the mean age at the time of diagnosis was 40 years. 60% presented other associated sleep disorders, the most frequent being SAHS (36%). The efficacy rate of treatment with continuous positive airway pressure (CPAP) is 66% in patients with SAHS with an indication of CPAP. CONCLUSIONS: Altogether, 60% of patients with narcolepsy have a second associated sleep disorder (greater than the incidence of coexistence in the general population, of 20-25% of patients), and those reported are also the most frequent among the general population (SAHS, restless legs syndrome, periodic limb movement disorder). 36% of patients with narcolepsy have SAHS as an associated condition. Of these, 78% have reached a suitable degree of control over respiratory events; 57% have achieved control with CPAP, and the remaining 43% did not require CPAP for event correction with other methods.


TITLE: Sindrome de apneas-hipopneas y narcolepsia. Descripcion de una serie hospitalaria.Introduccion. Los trastornos del sueño son muy prevalentes en la poblacion general; sin embargo, la asociacion de sindrome de apneas-hipopneas (SAHS) en pacientes con narcolepsia se ha descrito en pocas ocasiones. Se revisan los trastornos del sueño encontrados en pacientes con narcolepsia, la prevalencia de SAHS asociado a estos pacientes y su respuesta a los tratamientos. Pacientes y metodos. Analisis descriptivo retrospectivo observacional de 25 pacientes, con diagnostico de narcolepsia, atendidos en nuestro centro desde octubre de 2012 hasta diciembre de 2016. Resultados. De 470 pacientes valorados en la consulta monografica de neurologia, hemos diagnosticado a 25 pacientes con narcolepsia (5,31%); el 65% eran hombres, y el 35%, mujeres. Edad media en el momento del diagnostico: 40 años. El 60% presenta otros trastornos del sueño asociados, el mas frecuente es el SAHS (36%). La eficacia del tratamiento con presion aerea positiva continua nasal (CPAP) es del 66% en los pacientes con SAHS con indicacion de CPAP. Conclusiones. El 60% de los pacientes con narcolepsia asocia un segundo trastorno del sueño (mayor que la incidencia de coexistencia en la poblacion general, del 20-25% de los pacientes), y los descritos tambien son los mas frecuentes en la poblacion general (SAHS, sindrome de piernas inquietas, movimientos periodicos de las piernas). El 36% de los pacientes con narcolepsia asocia SAHS. De ellos, en el 78% se ha conseguido un control de eventos respiratorios adecuado; el 57% se ha controlado con CPAP y el 43% restante no ha precisado CPAP por correccion de eventos con otros metodos.


Assuntos
Narcolepsia/complicações , Apneia Obstrutiva do Sono/complicações , Adulto , Idoso , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Apneia Obstrutiva do Sono/terapia
18.
Front Plant Sci ; 7: 1016, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27524985

RESUMO

Maize (Zea mays L.) is the staple diet of the native peasants in the Quechua region of the Peruvian Andes who continue growing it in small plots called chacras following ancestral traditions. The abundance and structure of bacterial communities associated with the roots of amilaceous maize has not been studied in Andean chacras. Accordingly, the main objective of this study was to describe the rhizospheric bacterial diversity of amilaceous maize grown either in the presence or the absence of bur clover cultivated in soils from the Quechua maize belt. Three 16S rRNA gene libraries, one corresponding to sequences of bacteria from bulk soil of a chacra maintained under fallow conditions, the second from the rhizosphere of maize-cultivated soils, and the third prepared from rhizospheric soil of maize cultivated in intercropping with bur clover were examined using pyrosequencing tags spanning the V4 and V5 hypervariable regions of the gene. A total of 26031 sequences were found that grouped into 5955 distinct operational taxonomic units which distributed in 309 genera. The numbers of OTUs in the libraries from the maize-cultivated soils were significantly higher than those found in the libraries from bulk soil. One hundred ninety seven genera were found in the bulk soil library and 234 and 203 were in those from the maize and maize/bur clover-cultivated soils. Sixteen out of the 309 genera had a relative abundance higher than 0.5% and the were (in decreasing order of abundance) Gp4, Gp6, Flavobacterium, Subdivision3 genera incertae sedis of the Verrucomicrobia phylum, Gemmatimonas, Dechloromonas, Ohtaekwangia, Rhodoferax, Gaiella, Opitutus, Gp7, Spartobacteria genera incertae sedis, Terrimonas, Gp5, Steroidobacter and Parcubacteria genera incertae sedis. Genera Gp4 and Gp6 of the Acidobacteria, Gemmatimonas and Rhodoferax were the most abundant in bulk soil, whereas Flavobacterium, Dechloromonas and Ohtaekwangia were the main genera in the rhizosphere of maize intercropped with bur clover, and Gp4, Subdivision3 genera incertae sedis of phylum Verrucomicrobia, Gp6 and Rhodoferax were the main genera in the rhizosphere of maize plants. Taken together, our results suggest that bur clover produces specific changes in rhizospheric bacterial diversity of amilaceous maize plants.

19.
Circulation ; 99(25): 3221-3, 1999 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-10385493

RESUMO

BACKGROUND: Repeat coronary artery bypass graft surgery (CABG) is associated with a high morbidity and mortality, rendering percutaneous treatment of saphenous vein graft (SVG) lesions an attractive alternative. However, percutaneous interventions of degenerated SVGs carries high risk of distal embolization. METHODS AND RESULTS: This study reports our initial experience with the PercuSurge GuardWire, a new device developed to prevent embolization during treatment of degenerated SVG. This device consists of a 190-cm-long, hollow 0.014-in guidewire with a central lumen connected to a distal occlusion balloon. A dedicated inflation device (the MicroSeal Adapter) was used to inflate the distal balloon and maintain complete lumen occlusion during balloon dilatation and stent implantation. A monorail aspiration catheter, connected to a vacuum syringe, was used to evacuate atherosclerotic and thrombotic debris. Angioplasty with stent implantation was performed in 15 degenerated SVGs (18 lesions). Procedural success was achieved in all patients with normal postprocedure flow (Thrombolysis in Myocardial Infarction grade 3). No distal embolization was observed. There were no major in-hospital adverse clinical events, including Q-wave or non-Q-wave myocardial infarction, emergency CABG, or death. All patients were asymptomatic at discharge. CONCLUSIONS: This preliminary series supports the feasible use of the PercuSurge GuardWire for retrieval of plaque debris and prevention of embolization in degenerated SVGs. The good tolerance of temporary occlusions without angiographic or clinical evidence of distal embolization represents encouraging early findings.


Assuntos
Angioplastia Coronária com Balão/efeitos adversos , Angioplastia Coronária com Balão/instrumentação , Doença das Coronárias/terapia , Embolia/etiologia , Embolia/prevenção & controle , Veia Safena/patologia , Veia Safena/transplante , Idoso , Angioplastia Coronária com Balão/métodos , Doença das Coronárias/cirurgia , Desenho de Equipamento , Estudos de Viabilidade , Feminino , Humanos , Inalação , Masculino , Pessoa de Meia-Idade , Stents , Resultado do Tratamento
20.
J Am Coll Cardiol ; 37(4): 1019-25, 2001 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-11263602

RESUMO

OBJECTIVES: This study was performed to investigate the causes of diffuse and aggressive intra-stent restenosis. BACKGROUND: Although restenosis is usually considered to be a dichotomous variable, there is clinical relevance to the severity of restenosis. It is not known which variables are predictive of diffuse or aggressive intra-stent restenosis. METHODS: A consecutive series of 456 coronary lesions with in-stent restenosis was evaluated for the type of restenosis using quantitative coronary angiography. Restenosis was defined as > or = 50% diameter stenosis at follow-up angiography, diffuse restenosis as a follow-up lesion length > or = 10 mm and aggressive restenosis as either an increase in lesion length from the original lesion or a restenotic narrowing tighter than the original. Clinical, anatomic and procedural characteristics were evaluated for lesions associated with these types of restenosis. RESULTS: Diffuse restenosis was associated with a smaller reference artery diameter, longer lesion length, female gender, longer stent length and the use of coil stents. Aggressive restenosis was more common in women, with the use of Wallstents and with long stent to lesion length ratios. Aggressive restenosis occurred earlier and was more closely associated with symptoms and myocardial infarctions than nonaggressive restenotic lesions. CONCLUSIONS: Markers for diffuse restenosis were also important markers for the presence of any restenosis. A long stent to lesion length ratio is an important marker for aggressive restenosis. When severe forms of in-stent restenosis occur, they tend to present earlier and with more symptoms, including myocardial infarction. More careful consideration of the type of in-stent restenosis may aid in identifying when alternative strategies may be useful.


Assuntos
Doença das Coronárias/terapia , Stents , Angiografia Coronária , Doença das Coronárias/diagnóstico por imagem , Doença das Coronárias/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva
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