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1.
Radiography (Lond) ; 29 Suppl 1: S81-S86, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36828748

RESUMO

INTRODUCTION: The healthcare support needs of the lesbian, gay, bisexual (LGB) and transgender community are becoming an emerging area of healthcare research. Providing person-centred care is World Health Organisation policy and as such it is important that Radiography services can demonstrate areas in which they are working with people to design, develop and feedback on the services that they receive. This research aimed to establish how cancer treatment impacted on the identities of LGB people, their experiences of care, and their engagement with developing a practitioner guide. METHODS: This cooperative inquiry is underpinned by person-centred philosophy and participatory research principles. Participants were nine lesbian, gay, and bisexual people affected by cancer. Each engaged in two facilitated, audio-recorded conversations to explore their experiences of cancer care. An analytical framework based on Mezirow's Transformational Theory was used to organise the data, followed by detailed content analysis to develop themes. RESULTS: Participants included men and women, aged 45-68, who had experienced different cancers. They explored how cancer treatment had impacted on them, and worked with the researcher and stakeholders to establish a seven-recommendation practitioner guide aimed at improving LGB people's care experiences. Their accounts revealed a broad range of issues that both corroborate and build on existing evidence. Themes highlighted expectations and experiences of both assumptions and prejudice in healthcare interactions. These experiences, along with misinterpretation of relationships with significant others, led to feelings of discomfort and reserve about self-expression. Findings of the research are presented in the following key areas: Dilemmas of attending oncology appointments; Inclusive experiences of care; and Formulation of the practitioner guide. CONCLUSION: The research findings enabled development of a national practitioner guide with the participants and key stakeholders to raise awareness of the needs of LGB persons affected by cancer and support better care. IMPLICATIONS FOR PRACTICE: By providing real-life accounts this research adds to understanding of how LGB persons interact with services, developing evidence to support cultural competence within the profession of Radiography and oncology services more broadly.


Assuntos
Homossexualidade Feminina , Neoplasias , Minorias Sexuais e de Gênero , Masculino , Humanos , Feminino , Bissexualidade , Atenção à Saúde , Neoplasias/terapia
3.
Nat Commun ; 13(1): 2989, 2022 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-35637190

RESUMO

Erebus volcano, Antarctica, with its persistent phonolite lava lake, is a classic example of an evolved, CO2-rich rift volcano. Seismic studies provide limited images of the magmatic system. Here we show using magnetotelluric data that a steep, melt-related conduit of low electrical resistivity originating in the upper mantle undergoes pronounced lateral re-orientation in the deep crust before reaching shallower magmatic storage and the summit lava lake. The lateral turn represents a structural fault-valve controlling episodic flow of magma and CO2 vapour, which replenish and heat the high level phonolite differentiation zone. This magmatic valve lies within an inferred, east-west structural trend forming part of an accommodation zone across the southern termination of the Terror Rift, providing a dilatant magma pathway. Unlike H2O-rich subduction arc volcanoes, CO2-dominated Erebus geophysically shows continuous magmatic structure to shallow crustal depths of < 1 km, as the melt does not experience decompression-related volatile supersaturation and viscous stalling.

4.
Curr Oncol ; 24(6): e494-e502, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29270058

RESUMO

BACKGROUND: As cure rates for breast cancer improve, there is increasing evidence that late effects of treatment-and impaired fertility in particular-are emerging as important concerns among young breast cancer survivors. Older reports have evaluated the occurrence of amenorrhea after treatment, but few data have been reported about the incidence of biochemical evidence for impaired ovarian function in patients who do not become overtly menopausal. METHODS: We conducted a cross-sectional study evaluating anti-Müllerian hormone (amh) in premenopausal chemotherapy-treated breast cancer survivors and control patients. Random serum levels of amh and other relevant clinical data were collected for 100 premenopausal chemotherapy-treated breast cancer survivors and 76 control subjects. Subgroup analyses were performed for women with regular menstrual cycles at the time of amh testing. RESULTS: After adjustment for age, amh was significantly lower in the overall group of patients receiving chemotherapy (p = 0.002) and in the subgroup reporting normal cycles (p = 0.03). Cyclophosphamide produced a significant dose-dependent reduction in amh (p < 0.001); trastuzumab was associated with increased amh in survivors with normal cycles. Overall, serum amh in survivors was roughly equivalent to that measured in control patients 12 years older. CONCLUSIONS: Young breast cancer survivors often experience significant impairment of ovarian function despite having normal menstrual cycles after treatment. Those results have important implications for patient counselling and the timing of possible referral to a fertility specialist.

5.
Parasite Immunol ; 39(10)2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28748530

RESUMO

Humoral immunity develops in the spleen during blood-stage Plasmodium infection. This elicits parasite-specific IgM and IgG, which control parasites and protect against malaria. Studies in mice have elucidated cells and molecules driving humoral immunity to Plasmodium, including CD4+ T cells, B cells, interleukin (IL)-21 and ICOS. IL-6, a cytokine readily detected in Plasmodium-infected mice and humans, is recognized in other systems as a driver of humoral immunity. Here, we examined the effect of infection-induced IL-6 on humoral immunity to Plasmodium. Using P. chabaudi chabaudi AS (PcAS) infection of wild-type and IL-6-/- mice, we found that IL-6 helped to control parasites during primary infection. IL-6 promoted early production of parasite-specific IgM but not IgG. Notably, splenic CD138+ plasmablast development was more dependent on IL-6 than germinal centre (GC) B-cell differentiation. IL-6 also promoted ICOS expression by CD4+ T cells, as well as their localization close to splenic B cells, but was not required for early Tfh-cell development. Finally, IL-6 promoted parasite control, IgM and IgG production, GC B-cell development and ICOS expression by Tfh cells in a second model, Py17XNL infection. IL-6 promotes CD4+ T-cell activation and B-cell responses during blood-stage Plasmodium infection, which encourages parasite-specific antibody production.


Assuntos
Linfócitos B/imunologia , Linfócitos T CD4-Positivos/imunologia , Interleucina-6/imunologia , Ativação Linfocitária/imunologia , Malária/imunologia , Plasmodium chabaudi/imunologia , Animais , Anticorpos Antiprotozoários/imunologia , Citocinas/metabolismo , Feminino , Imunidade Humoral/imunologia , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Proteína Coestimuladora de Linfócitos T Induzíveis/metabolismo , Interleucina-6/genética , Interleucinas/imunologia , Malária/parasitologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Baço/imunologia , Sindecana-1/metabolismo
6.
Acad Radiol ; 24(2): 232-245, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28395794

RESUMO

We present an overview of the Centers for Quantitative Imaging Excellence (CQIE) program, which was initiated in 2010 to establish a resource of clinical trial-ready sites within the National Cancer Institute (NCI)-designated Cancer Centers (NCI-CCs) network. The intent was to enable imaging centers in the NCI-CCs network capable of conducting treatment trials with advanced quantitative imaging end points. We describe the motivations for establishing the CQIE, the process used to initiate the network, the methods of site qualification for positron emission tomography, computed tomography, and magnetic resonance imaging, and the results of the evaluations over the subsequent 3 years.


Assuntos
Imageamento por Ressonância Magnética/normas , Neoplasias/diagnóstico , Tomografia por Emissão de Pósitrons/normas , Tomografia Computadorizada por Raios X/normas , Institutos de Câncer/normas , Ensaios Clínicos como Assunto/normas , Desenho de Equipamento , Humanos , National Cancer Institute (U.S.) , Neoplasias/terapia , Imagens de Fantasmas , Estados Unidos
8.
J Anim Sci ; 94(12): 5239-5247, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28046168

RESUMO

The AA requirements of reproducing females are likely influenced by genetics, number of embryos and fetuses, and their nutritional needs during development. Hence, it is important to determine the change in AA concentration during development. Fetuses from a total of 26 second-parity sows were used to determine their AA composition at various stages of pregnancy. Yorkshire × Landrace sows were bred to Duroc boars and killed at 45, 62, 80, and 100 d of gestation, and fetal weights were determined. The pigs from 6 litters were killed prior to nursing the sow. The number of fetuses ranged from 10 to 13 pigs/litter. Pigs were combined by litter, ground, and freeze-dried, and AA was determined by gas chromatography. Litter was the experimental unit, and statistics were conducted using the GLM model of SAS with the best fitting regression equation estimates for each AA determined. Individual pigs (average/litter), litter, grams per 100 g total AA, and the ratio of each AA to Lys were statistically determined. Although the regression of individual pigs and litters were significant in a quadratic, cubic, or quartic manner ( < 0.01 to < 0.05), the general trend was a quadratic increase in total essential AA (EAA) and nonessential AA (NEAA) from 45 d to birth. All AA increased rapidly from 80 d of gestation, and more than 50% of total fetal growth occurred from 80 d to birth. Three AA (Arg, Leu, and Lys) constituted more than half of the total EAA from 80 d of gestation to birth compared with the other EAA. Overall, the NEAA increased more rapidly as pregnancy progressed than the EAA, with Pro, Hyp, and Gly increasing at a faster rate. When expressed in a ratio of Lys to the other AA, both Arg and Leu had a greater ratio increase than Lys. These results demonstrated that 50% of the total amount of EAA in the fetal pig increased during the last 2 wk of gestation and that Arg and Leu increased at a greater rate than Lys. The NEAA increased at a faster rate than the EAA throughout pregnancy.


Assuntos
Aminoácidos/análise , Desenvolvimento Fetal , Suínos/fisiologia , Aminoácidos/metabolismo , Animais , Cruzamento , Feminino , Peso Fetal , Feto , Tamanho da Ninhada de Vivíparos , Masculino , Paridade , Gravidez , Reprodução
10.
Prenat Diagn ; 35(9): 859-63, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25989740

RESUMO

OBJECTIVES: Prenatal diagnosis of critical congenital heart disease, which requires surgical or catheter intervention in the first 30 days of life, allows for delivery at a specialized center and can reduce preoperative morbidity and mortality. We sought to identify the risk factors for a missed prenatal diagnosis of critical congenital heart disease. METHODS: Patients presenting to the Children's Hospital of Wisconsin with critical congenital heart disease from 2007 to 2013 were included. Those with a prenatal diagnosis were compared with those with a postnatal diagnosis. RESULTS: The cohort included 535 patients with prenatal diagnosis made in 326 (61%). The prenatal diagnostic rate improved from 44% in 2007 to 69% in 2013. Independent factors associated with a postnatal diagnosis were a lesion that required a view other than a four chamber view to make the diagnosis (p < 0.0001), absence of another organ system anomaly (p < 0.0001), and living in a higher poverty (p = 0.02) or lower population density communities (p = 0.002). CONCLUSIONS: While the prenatal diagnostic rate for critical congenital heart disease is improving, those living in impoverished or rural communities are at highest risk of not having a diagnosis made prenatally. Interventions to improve prenatal detection of congenital heart disease should target these vulnerable areas.


Assuntos
Diagnóstico Tardio/estatística & dados numéricos , Disparidades em Assistência à Saúde/estatística & dados numéricos , Cardiopatias Congênitas/diagnóstico por imagem , Ultrassonografia Pré-Natal , Feminino , Cardiopatias Congênitas/terapia , Humanos , Recém-Nascido , Masculino , Análise Multivariada , Gravidez , Estudos Retrospectivos , Fatores de Risco , Fatores Socioeconômicos , Wisconsin
11.
J Anim Sci ; 93(3): 1149-56, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26020892

RESUMO

Graded levels of a trace mineral premix containing an organic (Bioplex) source of Cu, Fe, Mn, and Zn was evaluated with additional treatments containing organic Zn or Fe. Grower-finisher pigs were fed from 25 to 115 kg BW. The number of pigs in the experiment, the breeding/genetics of the pigs, the management, and the average age of the pigs were previously reported. The experiment was conducted as a randomized complete block design in 7 replicates. Treatments were 1) basal diet without supplemental Cu, Fe, Mn, and Zn; 2) basal diet + 2.5 mg/kg Cu, 50 mg/kg Fe, 1.5 mg/kg Mn, and 40 mg/kg Zn (50% NRC); 3) basal diet + 5 mg/kg Cu, 100 mg/kg Fe, 3 mg/kg Mn, and 80 mg/kg Zn (100% NRC); 4) basal diet + 25 mg Zn/kg; 5) basal diet + 50 mg Zn/kg; and 6) basal diet + 50 mg Fe/kg. Selenium and I were added to all diets at 0.3 and 0.14 mg/kg, respectively. Diets were composed of corn-soybean meal, dicalcium phosphate, and limestone with phytase added to enhance mineral availability. Three pigs per pen were bled at 55, 80, and 115 kg BW and plasma was analyzed for microminerals. When the average replicate BW was 115 kg, 3 pigs per pen of an equal gender ratio were killed. The liver, kidney, and heart were removed and analyzed for microminerals. Liver, duodenum, and jejunal metallothionein and the antioxidant enzymes in the liver containing these microminerals were determined. The results demonstrated that plasma minerals were unaffected at the 3 BW intervals. Liver and duodenum metallothionein protein were greater ( < 0.05) as dietary micromineral levels increased but jejunum metallothionein did not change as microminerals increased. The activity of Cu/Zn superoxide dismutase (SOD) was not affected as the levels of the micromineral increased, whereas the activity of Mn SOD increased slightly ( < 0.05) to the 50% NRC treatment level. Liver Zn (relative and total) increased ( < 0.05) as dietary micromineral levels increased and also when Zn was added singly to the diet. Liver, kidney, and heart Cu and Mn concentrations were similar at the various micromineral levels. The activities of liver enzymes containing graded levels of Zn were not affected by dietary microminerals at 115 kg BW. These results indicate that the supplemental levels of Cu, Fe, and Mn were not necessary for grower-finisher pigs and that these innate microminerals in a corn-soybean meal diet were adequate, whereas a need for supplemental Zn was demonstrated.


Assuntos
Fígado/efeitos dos fármacos , Fígado/enzimologia , Metalotioneína/metabolismo , Minerais/metabolismo , Minerais/farmacologia , Suínos/metabolismo , Animais , Cobre/análise , Cobre/metabolismo , Cobre/farmacologia , Suplementos Nutricionais , Feminino , Intestino Delgado/química , Ferro/análise , Ferro/metabolismo , Ferro/farmacologia , Rim/química , Masculino , Manganês/análise , Manganês/metabolismo , Manganês/farmacologia , Minerais/análise , Miocárdio/química , National Academy of Sciences, U.S. , Superóxido Dismutase/metabolismo , Estados Unidos , Zinco/análise , Zinco/metabolismo , Zinco/farmacologia
12.
J Anim Sci ; 93(1): 185-96, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25568367

RESUMO

Two experiments were conducted to determine the effects of increasing the dietary Zn content on growth performance, carcass characteristics, plasma Zn, and ileal mucosal inflammation mRNA expression of finishing pigs fed diets containing ractopamine HCl (RAC; Elanco Animal Health, Greenfield, IN). In Exp. 1, 312 pigs (327 × 1050; PIC, Hendersonville, TN; 94 kg BW) were used in a 27-d study. There were 2 pigs per pen and 26 pens per treatment. Treatments included a corn-soybean meal diet (control; 0.66% standardized ileal digestible [SID] Lys); a diet (0.92% SID Lys) with 10 mg/kg RAC; and the RAC diet plus 50, 100, or 150 mg Zn/kg from ZnO or 50 mg Zn/kg from a Zn AA complex (ZnAA; Availa-Zn; Zinpro, Eden Prairie, MN). All diets also contained 83 mg Zn/kg from ZnSO4 in the trace mineral premix. Pigs fed the RAC diet without added Zn had increased (P < 0.05) ADG, G:F, HCW, carcass yield, and loin weight compared with pigs fed the control diet. Increasing Zn from ZnO in diets containing RAC tended to increase (linear, P = 0.067) G:F and loin weight (quadratic, P = 0.064). Pigs fed diets with 50 mg Zn/kg from ZnAA tended to have increased (P = 0.057) ADG compared with pigs fed the RAC diet. In Exp. 2, 320 pigs (327 × 1050; PIC; 98 kg BW) were used in a 35-d study. There were 2 pigs per pen and 20 pens per treatment. Treatments included a control diet (0.66% SID Lys); a diet (0.92% SID Lys) with 10 mg/kg RAC; or the RAC diet plus 75, 150, and 225 mg Zn/kg from ZnO or ZnAA. All diets also contained 55 mg Zn/kg from ZnSO4 from the trace mineral premix. Pigs fed the RAC diet had increased (P < 0.05) ADG, G:F, HCW, loin depth, percentage lean, and liver weight compared with pigs fed the control diet. No Zn level or source effects or level × source interactions were observed for growth performance. A Zn level × source interaction (quadratic, P = 0.007) was observed in liver Zn concentrations. This resulted from liver Zn concentrations plateauing at 150 mg Zn/kg when ZnO was supplemented, while there was a linear increase when using ZnAA. Increasing Zn in diets containing RAC increased (linear, P < 0.05) plasma Zn on d 18 and 32. The expression of IL-1ß was increased (P = 0.014) in mucosa of pigs fed the RAC diet compared with those fed the control diet. Expression of IL-1ß decreased (linear, P = 0.026) in the mucosa of pigs fed increasing added Zn. In conclusion, adding Zn to diets containing RAC resulted in a trend for improved growth performance of pigs in 1 of 2 experiments. Also, additional Zn increased plasma Zn and reduced IL-1ß.


Assuntos
Composição Corporal/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Suplementos Nutricionais , Ileíte/metabolismo , Fenetilaminas/farmacologia , RNA Mensageiro/metabolismo , Suínos/crescimento & desenvolvimento , Zinco/farmacologia , Ração Animal , Fenômenos Fisiológicos da Nutrição Animal , Animais , Dieta/veterinária , Íleo/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Mucosa Intestinal/metabolismo , Fígado/metabolismo , RNA Mensageiro/genética , Suínos/metabolismo , Zinco/administração & dosagem , Zinco/metabolismo
13.
Epidemiol Infect ; 143(7): 1477-85, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25195643

RESUMO

There exists an urgent need to develop iterative risk assessment strategies of zoonotic diseases. The aim of this study is to develop a method of prioritizing 98 zoonoses derived from animal pathogens in Japan and to involve four major groups of stakeholders: researchers, physicians, public health officials, and citizens. We used a combination of risk profiling and analytic hierarchy process (AHP). Profiling risk was accomplished with semi-quantitative analysis of existing public health data. AHP data collection was performed by administering questionnaires to the four stakeholder groups. Results showed that researchers and public health officials focused on case fatality as the chief important factor, while physicians and citizens placed more weight on diagnosis and prevention, respectively. Most of the six top-ranked diseases were similar among all stakeholders. Transmissible spongiform encephalopathy, severe acute respiratory syndrome, and Ebola fever were ranked first, second, and third, respectively.


Assuntos
Interpretação Estatística de Dados , Prioridades em Saúde , Zoonoses/prevenção & controle , Animais , Feminino , Doença pelo Vírus Ebola/prevenção & controle , Humanos , Incidência , Japão , Masculino , Doenças Priônicas/prevenção & controle , Saúde Pública , Medição de Risco , Síndrome Respiratória Aguda Grave/prevenção & controle , Inquéritos e Questionários
14.
Immunol Cell Biol ; 93(2): 198-212, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25385067

RESUMO

Interleukin-17A (IL-17A) is a pro-inflammatory cytokine that has an important role at mucosal sites in a wide range of immune responses including infection, allergy and auto-immunity. γδ T cells are recognized as IL-17 producers, but based on the level of CD3 expression, we now define the remarkable ability of a CD3(bright) γδ T-cell subset with an effector memory phenotype to rapidly produce IL-17A, but not interferon-γ. CD3(bright) γδ T cells uniformly express the canonical germline encoded Vγ6/Vδ1(+) T-cell receptor. They are widely distributed with a preferential representation in the lungs and skin are negatively impacted in the absence of retinoic acid receptor-related orphan receptor gammat expression or endogenous flora. This population responded rapidly to various stimuli in a mechanism involving IL-23 and NOD-like receptor family, pyrin domain containing 3 (NLRP3)-inflammasome-dependent IL-1ß. Finally, we demonstrated that IL-17-producing CD3(bright) γδ T cells responded promptly and strongly to pneumococcal infection and during skin inflammation. Here, we propose a new way to specifically analyze IL-17-producing Vγ6/Vδ1(+) T cells based on the level of CD3 signals. Using this gating strategy, our data reinforce the crucial role of this γδ T-cell subset in respiratory and skin disorders.


Assuntos
Complexo CD3/metabolismo , Interleucina-17/biossíntese , Receptores de Antígenos de Linfócitos T gama-delta/metabolismo , Linfócitos T/imunologia , Sequência de Aminoácidos , Aminoquinolinas/farmacologia , Animais , Complexo CD3/química , Proteínas de Transporte/metabolismo , Células Germinativas/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Imiquimode , Imunidade , Inflamassomos/efeitos dos fármacos , Inflamassomos/metabolismo , Interleucina-1beta/metabolismo , Interleucina-23 , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Subpopulações de Linfócitos/efeitos dos fármacos , Subpopulações de Linfócitos/imunologia , Masculino , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Proteína 3 que Contém Domínio de Pirina da Família NLR , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Fenótipo , Pele/efeitos dos fármacos , Pele/imunologia , Linfócitos T/efeitos dos fármacos
16.
Drug Saf ; 38(1): 87-100, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25539877

RESUMO

BACKGROUND: Pharmacovigilance signal detection largely relies on individual case reports, but longitudinal health data are being explored as complementary information sources. Research to date has focused on the ability of epidemiological methods to distinguish established adverse drug reactions (ADRs) from unrelated adverse events. OBJECTIVE: The aim of this study was to evaluate a process for structured clinical and epidemiological assessment of temporally associated drugs and medical events in electronic medical records. METHODS: Pairs of drugs and medical events were selected for review on the basis of their temporal association according to a calibrated self-controlled cohort analysis in The Health Improvement Network. Six assessors trained in pharmacovigilance and/or epidemiology evaluated seven drugs each, with up to 20 medical events per drug. A pre-specified questionnaire considered aspects related to the nature of the temporal pattern, demographic features of the cohort, concomitant medicines, earlier signs and symptoms, and possible confounding by underlying disease. This informed a classification of drug-event pairs as known ADRs, meriting further evaluation, or dismissed. RESULTS: The number of temporally associated medical events per drug ranged from 11 to 307 (median 50) for the 42 selected drugs. Out of the 509 relevant drug-event combinations subjected to the assessment, 127 (25 %) were classified as known ADRs. Ninety-one (24 %) of the remaining pairs were classified as potential signals meriting further evaluation and 291 (76 %) were dismissed. Suggestive temporal patterns and lack of clear alternative explanations were the most common reasons that drug-event pairs were classified as meriting further evaluation. Earlier signs and symptoms and confounding by the underlying disease were the most common reasons that drug-event pairs were dismissed. CONCLUSIONS: Exploratory analysis of electronic medical records can detect important potential safety signals. However, effective signal detection requires that statistical signal detection be combined with clinical and epidemiological review to achieve an acceptable false positive rate.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Registros Eletrônicos de Saúde/estatística & dados numéricos , Farmacovigilância , Humanos , Estudos Prospectivos , Inquéritos e Questionários
17.
Medchemcomm ; 5(9): 1337-1346, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25431648

RESUMO

To investigate panitumumab-IRDye800 as an intraoperative optical imaging agent for epidermal growth factor receptor (EGFR)-expressing cancers, we developed clinical-quality panitumumab-IRDye800 and evaluated its specificity and sensitivity to visualize tumors by fluorescence imaging in a variety of mouse xenograft models with different levels of EGFR-expression. Panitumumab was chemically conjugated to NIR-dye (Li-COR 800CW) at well-defined and limited substitution ratio (1:1-2) for the characterization of fluorescence signals. Yield and purity of the conjugate was 80±5% and 95±2% respectively (n= 6). Quality control (QC) tests showed that product was suitable for clinical development. Female athymic nude xenograft tumor bearing mice (n=5 per tumor model) with very low (BT-474), moderate (MDA-MB-231), and high (MDA-MB-468) EGFR-expression levels were administered panitumumab-IRDye800 formulations (100 µg of mAb in 100 µL of 0.9% saline) via tail-vein injection. Animal imaging and biodistribution experiments were conducted on the FMT 2500 (Perkin Elmer) fluorescence scanner at 24, 48, 72, 96, and 144 hours post injection. Immuno-fluorescence images of panitumumab-IRDye conjugate recorded in mouse xenograft models showed a good correlation (R2 = 0.91) between EGFR-expression level and tumor uptake. Uptake of panitumumab labeled with IR-Dye or [89Zr] in different tumor xenografts with high, medium, and low EGFR expression, as measured by fluorescence or radioactive counts are highly correlated (r2= 0.99). This preclinical in-vivo study proved that panitumumab-IRDye800 is specific and optical imaging in conjunction with this probe is sensitive enough to detect EGFR-expressing tumors.

18.
J Anim Sci ; 92(10): 4486-93, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25149347

RESUMO

Inclusion of up to 0.38% S in diets that contain 30% distillers dried grains with solubles (DDGS) has no negative effect on growth performance of growing-finishing pigs, but there is no information about the effects of dietary S on accumulation of S in tissues in pigs. Therefore, the objective of this experiment was to determine if the concentration of S in diets containing DDGS affects carcass characteristics, loin quality, or tissue mineral concentrations in growing-finishing pigs. A total of 120 barrows (34.2 ± 2.3 kg BW) were allotted to 3 dietary treatments with 10 replicate pens and 4 pigs per pen in a randomized complete block design. Pigs were fed grower diets for 42 d and finisher diets for 42 d. At the conclusion of the experiment, the pig in each pen with the BW closest to the pen average was slaughtered. The control diet was based on corn and soybean meal and the finisher diet contained 0.14% S, 0.19 mg/kg Se, and 15.3 mg/kg Cu. The DDGS diet was formulated with corn, soybean meal, and 30% DDGS and the finisher diet with DDGS contained 0.16% S, 0.32 mg/kg Se, and 14.0 mg/kg Cu. The DDGS plus S (DDGS-S) diet was similar to the DDGS diet, except that 1.10% CaSO4 (16.2% S) was included in this diet, and the finisher diet with DDGS-S contained 0.37% S, 0.35 mg/kg Se, and 13.8 mg/kg Cu. Results indicated that organ weights and loin quality, 24-h pH, drip loss, loin subjective color, marbling, and firmness did not differ among treatments, but loin a* was greater (P < 0.05) for pigs fed the control diet than for pigs fed the DDGS-S diet. Concentrations of S in hair, liver, heart, loin, and all other tissues did not differ among treatments, but urinary S concentration was greater (P < 0.05) for pigs fed the DDGS-S diet than for pigs fed the other diets. Pigs fed the DDGS diet or the DDGS-S diet had greater (P < 0.01) concentrations of Se in hair, liver, heart, and loin than pigs fed the control diet, but liver concentrations of Cu did not differ among treatments. In conclusion, inclusion of 30% DDGS in diets fed to growing-finishing pigs did not influence carcass characteristics or tissue S concentrations regardless of S concentration in the diet, and excess dietary S was excreted in the urine. However, because of the greater concentration of Se in DDGS than in corn and soybean meal and, therefore, greater concentrations in DDGS-containing diets, tissue concentrations of Se were increased in pigs fed diets that contained DDGS. In contrast, dietary DDGS did not influence liver concentrations of Cu.


Assuntos
Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal/fisiologia , Dieta/veterinária , Grão Comestível/metabolismo , Enxofre/farmacologia , Sus scrofa/crescimento & desenvolvimento , Tecido Adiposo/efeitos dos fármacos , Animais , Composição Corporal/efeitos dos fármacos , Cobre/metabolismo , Carne , Selênio/metabolismo , Glycine max/química , Suínos , Zea mays/química
19.
Eur J Vasc Endovasc Surg ; 48(2): 147-52, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24882423

RESUMO

OBJECTIVES: Despite a decreasing incidence of abdominal aortic aneurysm (AAA), the cost-effectiveness of AAA ultrasound screening can be improved by reducing the screening costs and increasing the uptake rates. The BVI 9600 (BVI) is a promising tool for this purpose as it is inexpensive and can detect AAA without a trained operator. This study aims to investigate whether the BVI can be used to detect AAA for the purpose of a low-cost outreach screening approach. METHODS: A total of 142 subjects had their abdominal aortae measured by five sonographers using the BVI and a conventional ultrasound machine. The examination included four anterior-posterior measurements at four equally spaced scanning locations from the xiphisternum to the umbilicus. The measurements produced by each machine were compared using Bland-Altman plots, followed by an analysis of the AAA detection performance. RESULTS: The BVI measured the aortic diameter to within 0.88-1.56 cm of the true diameter, exceeding the 0.5 cm "clinically acceptable difference" (CAD). Its accuracy was poorer when measuring the aneurysmal aortae (mean difference -0.56 cm, variability 1.72 cm) than normal aortae (mean difference 0.02 cm, variability 0.76 cm). Nine out of 52 aneurysms were not detected due to undersizing measurement and non-visualization of the aortae. CONCLUSIONS: At present, the BVI is not sufficiently accurate to detect AAA for screening purposes. A number of technical features require improvement.


Assuntos
Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Dilatação Patológica , Desenho de Equipamento , Humanos , Variações Dependentes do Observador , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Ultrassonografia
20.
J Anim Sci ; 92(4): 1582-94, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24663209

RESUMO

Zinc is the trace element involved in more biological functions than any other micromineral in the nutrition of the newly weaned pig. Its role in growth via protein synthesis and antioxidant defense makes it a key nutrient in the diet of the newly weaned nursery pig for maximum lean tissue growth and health. In this study, 500 pigs (5 pigs/pen) were weaned at approximately 18 d of age and fed 0, 25, 50, 75, or 100 mg/kg of Zn supplied as organic or inorganic Zn or 50 mg Zn/kg combination with 50% Zn from each source. Pigs were killed at 0, 10, and 35 d of the study to determine mineral tissue concentrations and antioxidant activity in the liver and the amount of metallothionein (MT) protein in the liver, duodenum, and jejunum. Growth performance did not differ for the pigs supplemented with Zn but were greater than those fed the basal diet with no added Zn (P ≤ 0.05). Hepatic Zn concentration was numerically maximized with 75 mg/kg of organic Zn, but 100 mg/kg of Zn of inorganic Zn was necessary to achieve a similar concentration. At d 10, Mn superoxide dismutase in pigs fed no supplemental Zn was lower than when pigs were fed organic Zn (P ≤ 0.05). Hepatic MT responded in a linear manner with organic Zn (P ≤ 0.01) and pigs fed the basal diet had less than those supplemented with Zn (P ≤ 0.01). Duodenal MT was greater at d 10 with organic Zn (P ≤ 0.01) than pigs fed the basal diet, and at d 35, there was a linear response to both organic and inorganic Zn (P ≤ 0.01). As expected, jejunal MT was reduced compared to this protein in the duodenum. The provision of Zn at 50 mg/kg from either source resulted in greater jejunal MT than when Zn was fed as a combination of both sources at the same concentration (P ≤ 0.05). Our data indicate that the needs of the nursery pig, that is, Zn requirements for health and well-being, have changed since the data used to establish the 2012 Nutrient Requirements of Swine (NRC, 2012) was published. Organic minerals are shown in this study to be managed biologically in a different manner than inorganic Zn (sulfate) in the young pig. The newly weaned pig, while changing nutritional sources and physical environments, has extremely high biological demand for antioxidant defense. Our data show that to maximize growth, health, and well-being, 75 mg/kg of organic Zn in a complex nursery diet benefits today's fast growing pigs with a very high lean tissue composition.


Assuntos
Suínos/crescimento & desenvolvimento , Zinco/farmacologia , Ração Animal , Animais , Antioxidantes/metabolismo , Dieta/veterinária , Suplementos Nutricionais , Feminino , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Masculino , Necessidades Nutricionais , Suínos/metabolismo , Zinco/administração & dosagem , Zinco/química
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