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1.
Rev Esp Anestesiol Reanim (Engl Ed) ; 69(3): 143-178, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35288050

RESUMO

Aortic pathology is always a challenge for the clinician, and must be diagnosed and treated by a multidisciplinary team due to the technical and technological complexity of the resources used. Ongoing efforts to implement a systematic, protocolized approach involving "Aortic teams" made up of cardiologists, cardiac surgeons, vascular surgeons, anaesthesiologists and radiologists, among others are now leading to improved outcomes. The aim of this consensus document drawn up by the Aortic working groups of the Spanish Society of Anaesthesiology, Resuscitation and Pain Therapy (SEDAR) and the Spanish Society of Thoracic and Cardiovascular Surgery (SECTCV) is to disseminate a set of working protocols. The latest consensus document of the European Association for Cardio-Thoracic Surgery (EACTS) and the European Society for Vascular Surgery (ESVS) define the concept of "AORTIC TEAM"(1). The aortic team should be closely involved from diagnosis to treatment and finally follow-up, and should be formed of cardiac and vascular surgeons working together with anaesthesiologists, cardiologists, radiologists and geneticists. Treatment of aortic pathologies should be centralised in large centres, because this is the only way to effectively understand the natural course of the disease, provide the entire range of treatment options under one umbrella and treat potential complications. A streamlined emergent care pathway (24/7 availability), adequate transportation and transfer capabilities, as well as rapid activation of the multidisciplinary team must be available. In light of the complexity and constant evolution of therapeutic options, we present this first version of the Anaesthesiology and surgical guidelines for surgery of the ascending aorta and aortic arch. Some questions will no doubt remain unanswered, and future versions will include new techniques that, though implemented in some centres, are still not widely recommended.


Assuntos
Anestesiologia , Anestésicos , Aorta Torácica/cirurgia , Consenso , Humanos , Dor
2.
Microb Ecol ; 83(1): 182-201, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33860847

RESUMO

Mosquitoes, the major vectors of viruses like dengue, are naturally host to diverse microorganisms, which play an important role in their development, fecundity, immunity, and vector competence. The composition of their microbiota is strongly influenced by the environment, particularly their aquatic larval habitat. In this study, we used 2×300 bp 16s Illumina sequencing to compare the microbial profiles of emerging adult Aedes aegypti mosquitoes and the water collected from common types of aquatic habitat containers in Puerto Rico, which has endemic dengue transmission. We sequenced 141 mosquito and 46 water samples collected from plastic containers, septic tanks, discarded tires, underground trash cans, tree holes, or water meters. We identified 9 bacterial genera that were highly prevalent in the mosquito microbiome, and 77 for the microbiome of the aquatic habitat. The most abundant mosquito-associated bacterial OTUs were from the families Burkholderiaceae, Pseudomonadaceae, Comamonadaceae, and Xanthomonadaceae. Microbial profiles varied greatly between mosquitoes, and there were few major differences explained by container type; however, the microbiome of mosquitoes from plastic containers was more diverse and contained more unique taxa than the other groups. Container water was significantly more diverse than mosquitoes, and our data suggest that mosquitoes filter out many bacteria, with Alphaproteobacteria in particular being far more abundant in water. These findings provide novel insight into the microbiome of mosquitoes in the region and provide a platform to improve our understanding of the fundamental mosquito-microbe interactions.


Assuntos
Aedes , Microbiota , Animais , Humanos , Larva , Mosquitos Vetores , Porto Rico , Água
3.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-34304902

RESUMO

Aortic pathology is always a challenge for the clinician, and must be diagnosed and treated by a multidisciplinary team due to the technical and technological complexity of the resources used. Ongoing efforts to implement a systematic, protocolized approach involving "Aortic teams" made up of cardiologists, cardiac surgeons, vascular surgeons, anaesthesiologists and radiologists, among others are now leading to improved outcomes. The aim of this consensus document drawn up by the Aortic working groups of the Spanish Society of Anaesthesiology, Resuscitation and Pain Therapy (SEDAR) and the Spanish Society of Thoracic and Cardiovascular Surgery (SECTCV) is to disseminate a set of working protocols. The latest consensus document of the European Association for Cardio-Thoracic Surgery (EACTS) and the European Society for Vascular Surgery (ESVS) define the concept of "AORTIC TEAM"(1). The aortic team should be closely involved from diagnosis to treatment and finally follow-up, and should be formed of cardiac and vascular surgeons working together with anaesthesiologists, cardiologists, radiologists and geneticists. Treatment of aortic pathologies should be centralised in large centres, because this is the only way to effectively understand the natural course of the disease, provide the entire range of treatment options under one umbrella and treat potential complications. A streamlined emergent care pathway (24/7 availability), adequate transportation and transfer capabilities, as well as rapid activation of the multidisciplinary team must be available. In light of the complexity and constant evolution of therapeutic options, we present this first version of the Anaesthesiology and surgical guidelines for surgery of the ascending aorta and aortic arch. Some questions will no doubt remain unanswered, and future versions will include new techniques that, though implemented in some centres, are still not widely recommended.

4.
BMC Cancer ; 21(1): 593, 2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-34030643

RESUMO

BACKGROUND: ATLAS evaluated the efficacy and safety of the PARP inhibitor rucaparib in patients with previously treated locally advanced/unresectable or metastatic urothelial carcinoma (UC). METHODS: Patients with UC were enrolled independent of tumor homologous recombination deficiency (HRD) status and received rucaparib 600 mg BID. The primary endpoint was investigator-assessed objective response rate (RECIST v1.1) in the intent-to-treat and HRD-positive (loss of genome-wide heterozygosity ≥10%) populations. Key secondary endpoints were progression-free survival (PFS) and safety. Disease control rate (DCR) was defined post-hoc as the proportion of patients with a confirmed complete or partial response (PR), or stable disease lasting ≥16 weeks. RESULTS: Of 97 enrolled patients, 20 (20.6%) were HRD-positive, 30 (30.9%) HRD-negative, and 47 (48.5%) HRD-indeterminate. Among 95 evaluable patients, there were no confirmed responses. However, reductions in the sum of target lesions were observed, including 6 (6.3%) patients with unconfirmed PR. DCR was 11.6%; median PFS was 1.8 months (95% CI, 1.6-1.9). No relationship was observed between HRD status and efficacy endpoints. Median treatment duration was 1.8 months (range, 0.1-10.1). Most frequent any-grade treatment-emergent adverse events were asthenia/fatigue (57.7%), nausea (42.3%), and anemia (36.1%). Of 64 patients with data from tumor tissue samples, 10 (15.6%) had a deleterious alteration in a DNA damage repair pathway gene, including four with a deleterious BRCA1 or BRCA2 alteration. CONCLUSIONS: Rucaparib did not show significant activity in unselected patients with advanced UC regardless of HRD status. The safety profile was consistent with that observed in patients with ovarian or prostate cancer. TRIAL REGISTRATION: This trial was registered in ClinicalTrials.gov (NCT03397394). Date of registration: 12 January 2018. This trial was registered in EudraCT (2017-004166-10).


Assuntos
Carcinoma de Células de Transição/tratamento farmacológico , Indóis/administração & dosagem , Inibidores de Poli(ADP-Ribose) Polimerases/administração & dosagem , Neoplasias da Bexiga Urinária/tratamento farmacológico , Administração Oral , Idoso , Proteína BRCA1/genética , Proteína BRCA2/genética , Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/secundário , Reparo do DNA , Feminino , Seguimentos , Humanos , Indóis/efeitos adversos , Perda de Heterozigosidade , Masculino , Pessoa de Meia-Idade , Inibidores de Poli(ADP-Ribose) Polimerases/efeitos adversos , Intervalo Livre de Progressão , Critérios de Avaliação de Resposta em Tumores Sólidos , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia
5.
Rev Esp Anestesiol Reanim (Engl Ed) ; 68(5): 258-279, 2021 05.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-33775419

RESUMO

Este artículo ha sido retirado por indicación del Editor Jefe de la revista, después de constatar que parte de su contenido había sido plagiado, sin mencionar la fuente original: European Heart Journal (2014) 35, 2873 926.: https://academic.oup.com/eurheartj/article/35/41/2873/407693#89325738 El autor de correspondencia ha sido informado de la decisión y está de acuerdo con la retirada del artículo. El Comité Editorial lamenta las molestias que esta decisión pueda ocasionar. Puede consultar la política de Elsevier sobre la retirada de artículos en https://www.elsevier.com/about/our-business/policies/article-withdrawal


Assuntos
Anestesia , Anestesiologia , Cirurgia Torácica , Aorta Abdominal , Consenso
7.
Clin Transl Oncol ; 23(4): 882-891, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32897497

RESUMO

BACKGROUND: The studies IMvigor 210 cohort 2 and IMvigor211 evaluated the efficacy of atezolizumab in patients with locally advanced or metastatic urothelial cancer (mUC) upon progression to platinum-based chemotherapy worldwide. Yet, the real impact of this drug in specific geographical regions is unknown. MATERIALS AND METHODS: We combined individual-level data from the 131 patients recruited in Spain from IMvigor210 cohort 2 and IMvigor211 in a pooled analysis. Efficacy and safety outcomes were assessed in the overall study population and according to PD-L1 expression on tumour-infiltrating immune cells. RESULTS: Full data were available for 127 patients; 74 (58%) received atezolizumab and 53 (42%) chemotherapy. Atezolizumab patients had a numerically superior median overall survival although not reaching statistical significance (9.2 months vs 7.7 months). No statistically significant differences between arms were observed in overall response rates (20.3% vs 37.0%) or progression-free survival (2.1 months vs 5.3 months). Nonetheless, median duration of response was superior for the immunotherapy arm (non-reached vs 6.4 months; p = 0.005). Additionally, among the responders, the 12-month survival rates seemed to favour atezolizumab (66.7% vs 19.9%). When efficacy was analyzed based on PD-L1 expression status, no significant differences were found. Treatment-related adverse events of any grade occurred more frequently in the chemotherapy arm [46/57 (81%) vs 44/74 (59%)]. CONCLUSION: Patients who achieved an objective response on atezolizumab presented a longer median duration of response and numerically superior 12 month survival rates when compared with chemotherapy responders along with a more favorable safety profile. PD-L1 expression did not discriminate patients who might benefit from atezolizumab.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Neoplasias Ureterais/tratamento farmacológico , Neoplasias Uretrais/tratamento farmacológico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos/efeitos adversos , Antígeno B7-H1/metabolismo , Carcinoma de Células de Transição/metabolismo , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/secundário , Estudos de Coortes , Feminino , Humanos , Linfócitos do Interstício Tumoral/metabolismo , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Espanha , Taxa de Sobrevida , Resultado do Tratamento , Neoplasias Ureterais/metabolismo , Neoplasias Ureterais/mortalidade , Neoplasias Ureterais/patologia , Neoplasias Uretrais/metabolismo , Neoplasias Uretrais/mortalidade , Neoplasias Uretrais/patologia , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia
8.
J Med Entomol ; 57(5): 1668-1670, 2020 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-32300803

RESUMO

We added a vector control component to our existing abundance model to simulate intensive vector control in Puerto Rico. Removing 20-30% of gravid females in the model matches observed 60-80% reductions. The model's capacity to reproduce vector control increases its utility for planning and evaluation strategies.


Assuntos
Culicidae , Modelos Teóricos , Controle de Mosquitos , Animais , Feminino , Masculino
9.
Sci Total Environ ; 669: 213-228, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-30878930

RESUMO

Saharan air masses can transport high amounts of mineral dust particles and biological material to the Iberian Peninsula. During winter, this kind of events is not very frequent and usually does not reach the northwest of the Peninsula. However, between 21 and 22 February 2016 and between 22 and 23 February 2017, two exceptional events were registered in León (Spain), which severely affected air quality. An integrative approach including: i) typical synoptic conditions; ii) aerosol chemical composition; iii) particle size distributions; iv) pollen concentration; v) aerosol optical depth (AOD); vi) radiative forcing and vii) estimation of the impact of aerosols in the respiratory tract, was carried out. In the global characterization of these events, the exceedance of the PM10 daily limit value, an increase in the coarse mode and a rise in the iron concentration were observed. On the 2016 event, an AOD and extinction-related Ångström exponent clearly characteristic of desert aerosol (1.1 and 0.05, respectively) were registered. Furthermore, pollen grains not typical of flowering plants in this period were identified. The chemical analysis of the aerosol from the 2017 event allowed us to confirm the presence of the main elements associated with mineral sources (aluminum, calcium, and silica concentrations). An increase in the SO42-, NO3- and Cl- concentrations during the Saharan dust intrusion was also noted. However, in this event, there was no presence of atypical pollen types. The estimated dust radiative forcing traduced a cooling effect for surface and atmosphere during both events, corroborated by trends of radiative flux measurements. The estimated impact on the respiratory tract regions of the high levels of particulate matter during both Saharan dust intrusions showed high levels for the respirable fraction.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Poeira/análise , Monitoramento Ambiental , Doenças Respiratórias/epidemiologia , Aerossóis/efeitos adversos , Aerossóis/análise , Humanos , Tamanho da Partícula , Material Particulado/efeitos adversos , Material Particulado/análise , Pólen , Doenças Respiratórias/induzido quimicamente , Estações do Ano , Espanha/epidemiologia , Luz Solar
10.
Med Vet Entomol ; 33(1): 68-77, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30225842

RESUMO

In Puerto Rico, the first records of the transmission of Chikungunya (CHIKV) and Zika (ZIKV) viruses were confirmed in May 2014 and December 2015, respectively. Transmission of CHIKV peaked in September 2014, whereas that of ZIKV peaked in August 2016. The emergence of these mosquito-transmitted arboviruses in the context of a lack of human population immunity allowed observations of whether the outbreaks were associated with Aedes aegypti (Diptera: Culicidae) densities and weather. Mosquito density was monitored weekly in four communities using sentinel autocidal gravid ovitraps (AGO traps) during 2016 in order to provide data to be compared with the findings of a previous study carried out during the 2014 CHIKV epidemic. Findings in two communities protected against Ae. aegypti using mass AGO trapping (three traps per house in most houses) were compared with those in two nearby communities without vector control. Mosquito pools were collected to detect viral RNA of ZIKV, CHIKV and dengue virus. In areas without vector control, mosquito densities and rates of ZIKV detection in 2016 were significantly higher, similarly to those observed for CHIKV in 2014. The density of Ae. aegypti in treated sites was less than two females/trap/week, which is similar to the putative adult female threshold for CHIKV transmission. No significant differences in mosquito density or infection rates with ZIKV and CHIKV at the same sites between years were observed. Although 2016 was significantly wetter, mosquito densities were similar.


Assuntos
Aedes , Febre de Chikungunya/epidemiologia , Epidemias , Controle de Mosquitos , Tempo (Meteorologia) , Infecção por Zika virus/epidemiologia , Aedes/fisiologia , Aedes/virologia , Animais , Febre de Chikungunya/virologia , Mosquitos Vetores/fisiologia , Mosquitos Vetores/virologia , Densidade Demográfica , Porto Rico/epidemiologia , Infecção por Zika virus/virologia
11.
Clin Transl Oncol ; 21(1): 64-74, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30565086

RESUMO

The goal of this article is to provide recommendations about the management of muscle-invasive (MIBC) and metastatic bladder cancer. New molecular subtypes of MIBC are associated with specific clinical-pathological characteristics. Radical cystectomy and lymph node dissection are the gold standard for treatment and neoadjuvant chemotherapy with a cisplatin-based combination should be recommended in fit patients. The role of adjuvant chemotherapy in MIBC remains controversial; its use must be considered in patients with high-risk who are able to tolerate a cisplatin-based regimen, and have not received neoadjuvant chemotherapy. Bladder-preserving approaches are reasonable alternatives to cystectomy in selected patients for whom cystectomy is not contemplated either for clinical or personal reasons. Cisplatin-based combination chemotherapy is the standard first-line protocol for metastatic disease. In the case of unfit patients, carboplatin-gemcitabine should be considered the preferred first-line chemotherapy treatment option, while pembrolizumab and atezolizumab can be contemplated for individuals with high PD-L1 expression. In cases of progression after platinum-based therapy, PD-1/PD-L1 inhibitors are standard alternatives. Vinflunine is another option when anti-PD-1/PD-L1 therapy is not possible. There are no data from randomized clinical trials regarding moving on to immuno-oncology agents.


Assuntos
Neoplasias Musculares/terapia , Guias de Prática Clínica como Assunto/normas , Neoplasias da Bexiga Urinária/terapia , Ensaios Clínicos como Assunto , Terapia Combinada , Gerenciamento Clínico , Humanos , Neoplasias Musculares/secundário , Invasividade Neoplásica , Prognóstico , Sociedades Médicas , Neoplasias da Bexiga Urinária/patologia
12.
Angiogenesis ; 21(4): 883-900, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30014172

RESUMO

VEGF induces normal or aberrant angiogenesis depending on its dose in the microenvironment around each producing cell in vivo. This transition depends on the balance between VEGF-induced endothelial stimulation and PDGF-BB-mediated pericyte recruitment, and co-expression of PDGF-BB normalizes aberrant angiogenesis despite high VEGF doses. We recently found that VEGF over-expression induces angiogenesis in skeletal muscle through an initial circumferential vascular enlargement followed by longitudinal splitting, rather than sprouting. Here we investigated the cellular mechanism by which PDGF-BB co-expression normalizes VEGF-induced aberrant angiogenesis. Monoclonal populations of transduced myoblasts, expressing similarly high levels of VEGF alone or with PDGF-BB, were implanted in mouse skeletal muscles. PDGF-BB co-expression did not promote sprouting and angiogenesis that occurred through vascular enlargement and splitting. However, enlargements were significantly smaller in diameter, due to a significant reduction in endothelial proliferation, and retained pericytes, which were otherwise lost with high VEGF alone. A time-course of histological analyses and repetitive intravital imaging showed that PDGF-BB co-expression anticipated the initiation of vascular enlargement and markedly accelerated the splitting process. Interestingly, quantification during in vivo imaging suggested that a global reduction in shear stress favored the initiation of transluminal pillar formation during VEGF-induced splitting angiogenesis. Quantification of target gene expression showed that VEGF-R2 signaling output was significantly reduced by PDGF-BB co-expression compared to VEGF alone. In conclusion, PDGF-BB co-expression prevents VEGF-induced aberrant angiogenesis by modulating VEGF-R2 signaling and endothelial proliferation, thereby limiting the degree of circumferential enlargement and enabling efficient completion of vascular splitting into normal capillary networks despite high VEGF doses.


Assuntos
Becaplermina/metabolismo , Proliferação de Células , Células Endoteliais , Músculo Esquelético , Neovascularização Fisiológica , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Camundongos , Camundongos SCID , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/citologia , Músculo Esquelético/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
13.
J Vet Intern Med ; 31(6): 1765-1770, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28921665

RESUMO

BACKGROUND: Oral administration of glucocorticoid alters serum cystatin C (sCysC) concentration in humans. OBJECTIVE: To determine if oral administration of prednisone alters sCysC in dogs without pre-existing renal disease. ANIMALS: Forty six dogs were included: 10 dogs diagnosed with steroid responsive meningitis arteritis (SRMA; group A), 20 dogs diagnosed of pituitary-dependent hyperadrenocorticism (PDH; group B), and 16 healthy control dogs (group C). METHODS: Retrospective observational study. SRMA diagnosed dogs were administered prednisone 4 mg/kg/24 h PO 7 days, reducing the dose to 2 mg/kg/24 h 7 days before medication withdrawal. In group A, sampling was performed at days 0, 7, 14 and a final control at day 21. Blood and urine samples were collected in the 3 groups, and in group A, sampling was performed at all time points (days 1, 7, 14, and 21). RESULTS: In group A, sCysC was significantly higher at day 7 compared to the control group (0.4 ± 0.04 mg/L vs. 0.18 ± 0.03 mg/L mean ± SEM respectively P < 0.01); sCysC values decreased to basal at day 14 when the dose was decreased and after 1 week of withdrawal of prednisone (0.27 ± 0.03 mg/L for group A at day 14 and 0.15 ± 0.02 mg/L at day 21; P > 0.05). Dogs with PDH included in group B did not have significant differences in sCysC (0.22 ± 0.03 mg/L) compared to control (P > 0.05). CONCLUSIONS AND CLINICAL IMPORTANCE: Oral administration of prednisone unlike altered endogenous glucocorticoid production, increases sCysC in dogs in a dose-dependent fashion.


Assuntos
Anti-Inflamatórios/uso terapêutico , Cistatina C/sangue , Doenças do Cão/sangue , Prednisona/uso terapêutico , Administração Oral , Hiperfunção Adrenocortical/tratamento farmacológico , Hiperfunção Adrenocortical/veterinária , Animais , Anti-Inflamatórios/efeitos adversos , Arterite/tratamento farmacológico , Arterite/veterinária , Doenças do Cão/tratamento farmacológico , Cães , Feminino , Masculino , Meningite/tratamento farmacológico , Meningite/veterinária , Prednisona/efeitos adversos , Estudos Retrospectivos
14.
Ann Oncol ; 28(7): 1517-1522, 2017 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-28419193

RESUMO

BACKGROUND: Despite the advent of immunotherapy in urothelial cancer, there is still a need to find effective cytotoxic agents beyond first and second lines. Vinflunine is the only treatment approved in this setting by the European Medicines Agency and taxanes are also widely used in second line. Cabazitaxel is a taxane with activity in docetaxel-refractory cancers. A randomized study was conducted to compare its efficacy versus vinflunine. PATIENTS AND METHODS: This is a multicenter, randomized, open-label, phase II/III study, following a Simon's optimal method with stopping rules based on an interim futility analysis and a formal efficacy analysis at the end of the phase II. ECOG Performance Status, anaemia and liver metastases were stratification factors. Primary objectives were overall response rate for the phase II and overall survival for the phase III. RESULTS: Seventy patients were included in the phase II across 19 institutions in Europe. Baseline characteristics were well balanced between the two arms. Three patients (13%) obtained a partial response on cabazitaxel (95% CI 2.7-32.4) and six patients (30%) in the vinflunine arm (95% CI 11.9-54.3). Median progression-free survival for cabazitaxel was 1.9 versus 2.9 months for vinflunine (P = 0.039). The study did not proceed to phase III since the futility analysis showed a lack of efficacy of cabazitaxel. A trend for overall survival benefit was found favouring vinflunine (median 7.6 versus 5.5 months). Grade 3- to 4-related adverse events were seen in 41% patients with no difference between the two arms. CONCLUSION: This phase II/III second line bladder study comparing cabazitaxel with vinflunine was closed when the phase II showed a lack of efficacy of the cabazitaxel arm. Vinflunine results were consistent with those known previously. TRIAL NUMBER: NCT01830231.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Taxoides/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Urotélio/efeitos dos fármacos , Vimblastina/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/secundário , Progressão da Doença , Intervalo Livre de Doença , Europa (Continente) , Feminino , Humanos , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Taxoides/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia , Urotélio/patologia , Vimblastina/efeitos adversos , Vimblastina/uso terapêutico
15.
Arch Soc Esp Oftalmol ; 92(4): 154-159, 2017 Apr.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-27956327

RESUMO

OBJECTIVE: To evaluate the results of applying retrobulbar chlorpromazine in the management of patients with painful blind eyes or with very poor vision. METHODS: A retrospective, descriptive review was carried out on the medical records of 33 patients who were treated with a retrobulbar injection of chlorpromazine (25mg) for the management of painful blind eyes in Centro Oftalmológico Virgilio Galvis. RESULTS: Pain control was achieved in 90% of cases (with mean follow-up of 2.1 years). The mean intraocular pressure decreased by 37%. In 7 out of 12 eyes that maintained residual vision, loss of some degree of vision was acknowledged. One patient required an additional cyclodestructive procedure, another one required an absolute alcohol injection, and in an additional case evisceration surgery was necessary to achieve pain control. No serious complications were noted with this therapy. CONCLUSIONS: Retrobulbar injection of chlorpromazine is a valid option in painful, blind eye cases (or with very poor vision) with a poor visual prognosis.


Assuntos
Cegueira/complicações , Clorpromazina/administração & dosagem , Dor Ocular/tratamento farmacológico , Dor Ocular/etiologia , Baixa Visão/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Injeções Intralesionais , Masculino , Pessoa de Meia-Idade , Nervo Óptico , Estudos Retrospectivos , Adulto Jovem
16.
Rev. chil. endocrinol. diabetes ; 8(4): 154-161, oct. 2015. tab, ilus
Artigo em Espanhol | LILACS | ID: biblio-831329

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is directly associated with insulin resistance and oxidative stress. In NAFLD is established a reduction in n-3 LCPUFA (EPA + DHA) levels and hepatic activity of transcription factor PPAR-alpha. EPA and DHA inhibit lipogenesis and stimulate fatty acid oxidation in the liver. Extra virgin olive oil (EVOO) has important antioxidant properties. This study evaluated the prevention of insulin resistance and prevention of depletion of hepatic antioxidant defense inC57BL/6J mice fed high-fat diet (HFD), supplemented with n-3 LCPUFA plus EVOO. HFD generated insulin resistance and hepatic steatosis, together with significant reduction in i) n-3 LCPUFA hepatic levels, ii) DNA binding activity of PPAR-alpha, iii) activity of antioxidant enzymes (catalase and superoxide dismutase), respect to control group (fed with control diet). Supplementation with n-3 LCPUFA plus EVOO prevent development insulin resistance and attenuate increased of fat in liver (p < 0.05), together with a normalization of i) DNA binding activity of PPAR-á, ii) activity of antioxidant enzymes (catalase and superoxide dismutase) and iii) reducing depletion of n-3 LCPUFA levels in liver tissue, compared to the control group (p < 0.05). Supplementation with n-3 LCPUFA plus EVOO reduced hepatic steatosis and prevent development of insulin resistance, along with preserving the antioxidant defense in liver. Projecting the use of this mixture of AGPICL n-3 plus EVOO as a potential treatment of NAFLD.


Assuntos
Masculino , Animais , Camundongos , Azeite de Oliva/uso terapêutico , /uso terapêutico , Dieta Hiperlipídica , Suplementos Nutricionais , Hepatopatia Gordurosa não Alcoólica/dietoterapia , Azeite de Oliva/farmacologia , /farmacologia , Catalase , Catalase/fisiologia , Fígado , Estresse Oxidativo , Superóxido Dismutase
17.
Eye (Lond) ; 29(7): 843-59, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25931166

RESUMO

Keratoconus has been classically defined as a progressive, non-inflammatory condition, which produces a thinning and steepening of the cornea. Its pathophysiological mechanisms have been investigated for a long time. Both genetic and environmental factors have been associated with the disease. Recent studies have shown a significant role of proteolytic enzymes, cytokines, and free radicals; therefore, although keratoconus does not meet all the classic criteria for an inflammatory disease, the lack of inflammation has been questioned. The majority of studies in the tears of patients with keratoconus have found increased levels of interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α), and matrix metalloproteinase (MMP)-9. Eye rubbing, a proven risk factor for keratoconus, has been also shown recently to increase the tear levels of MMP-13, IL-6, and TNF-α. In the tear fluid of patients with ocular rosacea, IL-1α and MMP-9 have been reported to be significantly elevated, and cases of inferior corneal thinning, resembling keratoconus, have been reported. We performed a literature review of published biochemical changes in keratoconus that would support that this could be, at least in part, an inflammatory condition.


Assuntos
Proteínas do Olho/metabolismo , Interleucina-6/metabolismo , Ceratite/fisiopatologia , Ceratocone/fisiopatologia , Metaloproteinase 9 da Matriz/metabolismo , Lágrimas/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Humanos , Ceratite/metabolismo , Ceratocone/metabolismo
18.
Food Funct ; 5(7): 1564-72, 2014 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-24855655

RESUMO

Alpha-linolenic acid (ALA) is an essential n-3 PUFA; its n-3 LCPUFA derivatives EPA and DHA, which have diverse beneficial effects, are scarce in the human diet. In recent years nontraditional vegetable oils rich in ALA (up to 45%) have been developed as new alternatives to increase ALA consumption. This work evaluated the accretion of ALA, EPA and DHA into the phospholipids extracted from erythrocytes, liver, kidney, small intestine, heart, quadriceps and the brain in rats fed sunflower (SFO), canola (CO), Rosa canina (RCO), sacha inchi (Plukenetia volubilis, SIO) and chia (Salvia hispánica, ChO) oils. Five experimental groups (n = 12 per group) were fed for 21 days with SFO (1% ALA), CO (10% ALA), RCO (33% ALA), SIO (49% ALA), and ChO (64% ALA). SIO and ChO allowed higher ALA accretion in all tissues, except the brain, and a reduction in the content of arachidonic acid in all tissues except the brain. EPA was increased in erythrocytes, liver, kidney, small intestine, heart and quadriceps, but not in the brain. DHA was increased in the liver, small intestine and brain tissues. Our results demonstrate that ALA, when provided in significant amounts, can be converted into n-3 LCPUFA, mostly DHA in the liver and brain. It is suggested that oils rich in ALA, such as SIO and ChO, are good sources for obtaining higher tissue levels of ALA, also allowing its selective conversion into n-3 LCPUFA in some tissues of the rat.


Assuntos
Euphorbiaceae/química , Óleos de Plantas/farmacologia , Rosa/química , Salvia/química , Ácido alfa-Linolênico/farmacologia , Animais , Ácido Araquidônico/análise , Ácido Araquidônico/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Ácidos Docosa-Hexaenoicos/análise , Ácidos Docosa-Hexaenoicos/farmacologia , Ácido Eicosapentaenoico/análise , Ácido Eicosapentaenoico/farmacologia , Coração/efeitos dos fármacos , Coração/fisiologia , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Fosfolipídeos/metabolismo , Ratos , Ratos Wistar , Ácido alfa-Linolênico/análise
19.
Ann Oncol ; 25(6): 1222-8, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24608201

RESUMO

BACKGROUND: Although sarcomas account for only 1% of all solid tumours, patients with sarcomas comprise a larger proportion of patients entering phase I trials, due to the limited number of registered or active drugs for these diseases. To help in patient selection, we evaluated the utility of the predictive Royal Marsden Score which had been derived in carcinoma patients. In addition, we analysed efficacy and toxicity regarding the sarcoma population enrolled in phase I trials. PATIENTS AND METHODS: We used data from a European Database comprising 2182 patients treated in phase I trials in 14 European institutions between 2005 and 2007. RESULTS: One hundred and seventy-eight patients diagnosed with advanced sarcoma or other mesenchymal tumours were identified and accounted for 217 phase I trial participations during the study period. Histological type, class of drug, number of metastatic sites, high serum lactate dehydrogenase activity (LDH), low albumin and high white blood cell count were independent prognostic factors. Poor performance status (PS), liver metastases and high leucocyte count were associated with increased risk of early death. The class of drug used was the strongest predictor of progression-free survival (PFS) duration, inhibitors of angiogenesis and histone deacetylase giving the best results. Poor PS, high serum LDH and low lymphocyte count correlated with shorter PFS. In this heterogeneous population, PFS with investigational agents appeared comparable with that previously published for patients receiving standard treatments beyond first line. CONCLUSION: Prognostic factors in sarcoma patients do not differ from a broader phase I population. Efficacy measures suggest that some patients with sarcoma derive benefit from therapy in this setting which could therefore be considered for patients with no remaining standard therapeutic option.


Assuntos
Ensaios Clínicos Fase I como Assunto , Sarcoma/tratamento farmacológico , Adulto , Idoso , Antineoplásicos/uso terapêutico , Bases de Dados Factuais , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
20.
Rev. chil. nutr ; 41(1): 85-89, mar. 2014. tab
Artigo em Espanhol | LILACS | ID: lil-710964

RESUMO

Polyunsaturated Omega-3 fatty acids (ω-3 PUFA), particularly docosahexaenoic acid (C22:6 ω-3, DHA), are critical nutrients during pregnancy with a key role for visual and brain development. Fish, especially oily fish, is an excellent dietary source of DHA. However, its dietary consumption is low. Bioconversion from alpha-linolenic acid (C18: 3 ω-3, ALA) to DHA is a limited metabolic pathway in humans, however, it increases during fertility and pregnancy. The chia seed oil (Salvia hispanica) is a good vegetal source of ω-3 PUFA, containing a large proportion (60-65% of total fatty acids) as ALA. The aim of this study was to compare the acceptability of two different commercial oils: chia oil (63% ALA) and canola oil (10% ALA) in a group of Chilean pregnant women. A sample of 41 women was included. Each participant performed: a) an assessment of the acceptability of two commercial oils (hedonic scale), b) a dietary intake questionnaire and, c) a test of knowledge related to ω-3 PUFAs. Main results indicated that 57% of the participants properly recognized food sources of ω-3 PUFA, and 12.2% met their dietary requirements. The characteristics that had the highest scores were the appearance of chia oil and the taste of canola oil. However, there were no significant differences between the overall acceptability of both evaluated oils. It is concluded that chia oil could be a new and useful alternative to increase dietary ALA intake in pregnant women.


Los ácidos grasos (AG) poliinsaturados omega 3 (AGPI ω-3), y especialmente el ácido docosahexaenoico (C22:6 ω-3, DHA) participan en el desarrollo cerebral y visual del feto y del lactante, constituyendo nutrientes críticos durante el embarazo. Los pescados grasos, representan una excelente fuente de consumo de DHA, sin embargo, su consumo a nivel poblacional es bajo. El ácido alfa-linolénico (C18:3 ω-3, ALA) es el precursor del DHA, vía metabólica limitada en el ser humano, pero que aumenta en mujeres en edad fértil y embarazadas. El aceite de semilla de chía (Salvia hispánica) contiene en una gran cantidad de AGPI ω-3 (60-65% del total de AG) y su aceite podría representar una nueva fuente de este tipo de AG. El objetivo de este estudio fue comparar la aceptabilidad de un aceite de canola (10% ALA) y chía (63% ALA) en embarazadas chilenas. Se estudió una muestra de 41 embarazadas quienes respondieron una encuesta de aceptabilidad (escala hedónica), una encuesta de tendencia de consumo modificada y una prueba de conocimiento respecto a los AGPI ω-3. Los resultados indicaron que el 57% de las embarazadas reconoció correctamente los alimentos fuentes de AGPI ω-3 y 12.2% de ellas cumplió con sus requerimientos dietarios. Las características que presentaron los mayores puntajes fueron la apariencia del aceite de chía, y el sabor del aceite de canola. Sin embargo, no existió diferencia significativa entre la aceptabilidad de ambos aceites evaluados. Se concluye que el aceite de chía podría ser utilizado como una alternativa dietaria de buena fuente de ALA en embarazadas.


Assuntos
Humanos , Sensação , Óleos de Plantas , Ácidos Linoleicos , Ingestão de Alimentos , Gestantes , Dieta Saudável
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