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1.
AJNR Am J Neuroradiol ; 40(12): 2102-2110, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31780462

RESUMO

BACKGROUND AND PURPOSE: Aneurysm growth has been related to higher rupture risk. A better understanding of the characteristics related to growth may assist in the treatment decisions of unruptured intracranial aneurysms. This study aimed to identify morphologic and hemodynamic characteristics associated with aneurysm growth and to determine whether these characteristics deviate further from those of stable aneurysms after growth. MATERIALS AND METHODS: We included 81 stable and 56 growing aneurysms. 3D vascular models were segmented on CTA, MRA, or 3D rotational angiographic images. With these models, we performed computational fluid dynamics simulations. Morphologic (size, size ratios, and shape) and hemodynamic (inflow, vorticity, shear stress, oscillatory shear index, flow instability) characteristics were automatically calculated. We compared the characteristics between aneurysms that were stable and those that had grown at baseline and final imaging. The significance level after Bonferroni correction was P < .002. RESULTS: At baseline, no significant differences between aneurysms that were stable and those that had grown were detected (P > .002). Significant differences between aneurysms that were stable and those that had grown were seen at the final imaging for shear rate, aneurysm velocity, vorticity, and mean wall shear stress (P < .002). The latter was 11.5 (interquartile range, 5.4-18.8 dyne/cm2) compared with 17.5 (interquartile range, 11.2-29.9 dyne/cm2) in stable aneurysms (P = .001). Additionally, a trend toward lower area weighted average Gaussian curvature in aneurysms that had grown was observed with a median of 6.0 (interquartile range, 3.2-10.7 cm-2) compared with 10.4 (interquartile range, 5.0-21.2 cm-2) in stable aneurysms (P = .004). CONCLUSIONS: Morphologic and hemodynamic characteristics at baseline were not associated with aneurysm growth in our population. After growth, almost all indices increase toward values associated with higher rupture risks. Therefore, we stress the importance of longitudinal imaging and repeat risk assessment in unruptured aneurysms.


Assuntos
Hemodinâmica/fisiologia , Aneurisma Intracraniano/patologia , Aneurisma Intracraniano/fisiopatologia , Idoso , Angiografia Cerebral/métodos , Progressão da Doença , Feminino , Humanos , Imageamento Tridimensional/métodos , Aneurisma Intracraniano/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Medição de Risco
2.
J Neuroimaging ; 29(4): 487-492, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31002750

RESUMO

BACKGROUND AND PURPOSE: Aneurysm hemodynamics play an important role in aneurysm growth and subsequent rupture. Within the available hemodynamic characteristics, particle residence time (PRT) is relatively unexplored. However, some studies have shown that PRT is related to thrombus formation and inflammation. The goal of this study is to evaluate the association between PRT and aneurysm rupture and morphology. METHODS: We determined the PRT for 113 aneurysms (61 unruptured, 53 ruptured) based on computational fluid dynamic models. Virtual particles were injected into the parent vessel and followed during multiple cardiac cycles. PRT was defined as the time needed for 99% of the particles that entered an aneurysm to leave the aneurysm. Subsequently, we evaluated the association between PRT, rupture, and morphology (aneurysm type, presence of blebs, or multiple lobulations). RESULTS: PRT showed no significant difference between unruptured (1.1 seconds interquartile range [IQR .39-2.0 seconds]) and ruptured aneurysms (1.2 seconds [IQR .47-2.3 seconds]). PRT was influenced by aneurysm morphology. Longer PRTs were seen in bifurcation aneurysms (1.3 seconds [IQR .54-2.4 seconds], P = .01) and aneurysms with blebs or multiple lobulations (1.92 seconds [IQR .94-2.8 seconds], P < .001). Four of five partially thrombosed aneurysms had a long residence time (>1.9 seconds). CONCLUSIONS: Our study shows an influence of aneurysm morphology on PRT. Nevertheless, it suggests that PRT cannot be used to differentiate unruptured and ruptured aneurysms.


Assuntos
Aneurisma Roto/diagnóstico por imagem , Angiografia Cerebral/métodos , Processamento de Imagem Assistida por Computador/métodos , Aneurisma Intracraniano/diagnóstico por imagem , Adulto , Idoso , Feminino , Hemodinâmica/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade
3.
AJNR Am J Neuroradiol ; 39(5): 910-915, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29599169

RESUMO

BACKGROUND AND PURPOSE: Hemodynamics are thought to play a role in intracranial aneurysm growth and rupture. Computational fluid dynamics is frequently performed to assess intra-aneurysmal hemodynamics, using generalized flow waveforms of healthy volunteers as inflow boundary conditions. The purpose of this study was to assess differences in inflow conditions for different aneurysmal parent artery locations and variations of circle of Willis configurations. MATERIALS AND METHODS: In a series of 96 patients with 103 aneurysms, velocity measurements were acquired using 2D phase-contrast MR imaging perpendicular to the aneurysmal parent arteries in the circle of Willis. Circle of Willis configurations were inspected for variations using multiple overlapping thin-slab-acquisition MRAs. Flow rates, velocity magnitudes, and pulsatility indices were calculated for each parent artery location in subgroups of complete and incomplete circle of Willis configurations. RESULTS: Flow rates, velocity magnitudes, and pulsatility indices were significantly different among aneurysmal parent arteries. Incomplete circle of Willis configurations were observed in 24% of the cases. Significantly lower basilar artery flow rates were observed in configurations with hypoplastic P1 segments. Significantly higher A1 flow rates were observed in configurations with a hypoplastic contralateral A1 segment. CONCLUSIONS: Inflow conditions vary substantially between aneurysmal parent arteries and circle of Willis configurations. We have created a collection of parent artery-specific inflow conditions tailored to the patient-specific circle of Willis configuration that can be used in future computational fluid dynamics studies analyzing intra-aneurysmal hemodynamics.


Assuntos
Circulação Cerebrovascular/fisiologia , Círculo Arterial do Cérebro/fisiopatologia , Hemodinâmica/fisiologia , Aneurisma Intracraniano/fisiopatologia , Adulto , Idoso , Círculo Arterial do Cérebro/patologia , Feminino , Humanos , Hidrodinâmica , Aneurisma Intracraniano/patologia , Masculino , Pessoa de Meia-Idade
4.
Environ Monit Assess ; 188(8): 463, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27406208

RESUMO

In June 2008, a surveillance study for metals in honeybees was performed in the Netherlands. Randomly, 150 apiaries were selected. In each apiary, five colonies were sampled. Per apiary, the hive samples were pooled. The apiary sample was analysed for Al, As, Ba, Cd, Co, Cr, Cu, Li, Mn, Mo, Ni, Sb, Se, Sn, Sr, Ti, V and Zn. All metals could be detected in all apiaries. As, Li, Sb, Sn and V were detected in part of the apiaries. The overall picture showed a regional pattern. In apiaries in the east of the Netherlands, Al, Ba, Cr, Mn, Mo, Ni, Se and Ti are found in higher concentrations compared to the west. In-region variation was demonstrated, indicating local effects. The vicinity of the apiaries was mapped afterwards and characterised as land uses of >50 % agricultural area, >50 % wooded area, >50 % urban area and mixed land use within a circle of 28 km(2) around the apiary. The results indicated that in apiaries located in >50 % wooded areas, significantly higher concentrations of Al, Ba, Cd, Cr, Cu, Li, Mn, Mo, Ni, Sb, Sr, Ti and Zn were found compared to agricultural, urban and mixed land use areas. We conclude that (1) the ratio between metal concentrations varies per region, demonstrating spatial differences, and (2) there is in-region local variation per metal. The results indicate the impact of land use on metal concentrations in honeybees. For qualitative bioindication studies, regional, local and land use effects should be taken into account.


Assuntos
Abelhas , Poluentes Ambientais/análise , Metais/análise , Animais , Arsênio/análise , Monitoramento Ambiental , Países Baixos
5.
J Labelled Comp Radiopharm ; 59(4): 175-86, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26991121

RESUMO

The 24th annual symposium of the International Isotope Society's United Kingdom Group took place at the Møller Centre, Churchill College, Cambridge, UK on Friday 6th November 2015. The meeting was attended by 77 delegates from academia and industry, the life sciences, chemical, radiochemical and scientific instrument suppliers. Delegates were welcomed by Dr Ken Lawrie (GlaxoSmithKline, UK, chair of the IIS UK group). The subsequent scientific programme consisted of oral presentations, short 'flash' presentations in association with particular posters and poster presentations. The scientific areas covered included isotopic synthesis, regulatory issues, applications of labelled compounds in imaging, isotopic separation and novel chemistry with potential implications for isotopic synthesis. Both short-lived and long-lived isotopes were represented, as were stable isotopes. The symposium was divided into a morning session chaired by Dr Rebekka Hueting (University of Oxford, UK) and afternoon sessions chaired by Dr Sofia Pascu (University of Bath, UK) and by Dr Alan Dowling (Syngenta, UK). The UK meeting concluded with remarks from Dr Ken Lawrie (GlaxoSmithKline, UK).

6.
AJNR Am J Neuroradiol ; 36(10): 1927-33, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26089313

RESUMO

BACKGROUND AND PURPOSE: Rupture risk of intracranial aneurysms may depend on hemodynamic characteristics. This has been assessed by comparing hemodynamic data of ruptured and unruptured aneurysms. However, aneurysm geometry may change before, during, or just after rupture; this difference causes potential changes in hemodynamics. We assessed changes in hemodynamics in a series of intracranial aneurysms, by using 3D imaging before and after rupture. MATERIALS AND METHODS: For 9 aneurysms in 9 patients, we used MRA, CTA, and 3D rotational angiography before and after rupture to generate geometric models of the aneurysm and perianeurysmal vasculature. Intra-aneurysmal hemodynamics were simulated by using computational fluid dynamics. Two neuroradiologists qualitatively assessed flow complexity, flow stability, inflow concentration, and flow impingement in consensus, by using flow-velocity streamlines and wall shear stress distributions. RESULTS: Hemodynamics changed in 6 of the 9 aneurysms. The median time between imaging before and after rupture was 678 days (range, 14-1461 days) in these 6 cases, compared with 151 days (range, 34-183 days) in the 3 cases with unaltered hemodynamics. Changes were observed for flow complexity (n = 3), flow stability (n = 3), inflow concentration (n = 2), and region of flow impingement (n = 3). These changes were in all instances associated with aneurysm displacement due to rupture-related hematomas, growth, or newly formed lobulations. CONCLUSIONS: Hemodynamic characteristics of intracranial aneurysms can be altered by geometric changes before, during, or just after rupture. Associations of hemodynamic characteristics with aneurysm rupture obtained from case-control studies comparing ruptured with unruptured aneurysms should therefore be interpreted with caution.


Assuntos
Aneurisma Roto/diagnóstico , Aneurisma Roto/fisiopatologia , Hemodinâmica/fisiologia , Aneurisma Intracraniano/diagnóstico , Aneurisma Intracraniano/fisiopatologia , Adolescente , Adulto , Angiografia Cerebral/métodos , Diagnóstico Diferencial , Feminino , Humanos , Hidrodinâmica , Imageamento Tridimensional , Angiografia por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Modelagem Computacional Específica para o Paciente , Estresse Mecânico , Adulto Jovem
7.
Chem Commun (Camb) ; 51(19): 4055-8, 2015 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-25660394

RESUMO

A pretargeted imaging strategy based on the HaloTag dehalogenase enzyme is described. Here, a HaloTag-Trastuzumab conjugate has been used as the primary agent targeting HER2 expression, and three new radiolabelled HaloTag ligands have been used as secondary agents, two of which offer dual-modality (SPECT/optical) imaging capability.


Assuntos
Anticorpos Monoclonais Humanizados/metabolismo , Halogênios/metabolismo , Hidrolases/metabolismo , Imagem Óptica/métodos , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Linhagem Celular Tumoral , Humanos , Ligantes , Trastuzumab
8.
Mol Plant Microbe Interact ; 27(4): 336-48, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24313955

RESUMO

Plant pathogens secrete effectors to manipulate their host and facilitate colonization. Fusarium oxysporum f. sp. lycopersici is the causal agent of Fusarium wilt disease in tomato. Upon infection, F. oxysporum f. sp. lycopersici secretes numerous small proteins into the xylem sap (Six proteins). Most Six proteins are unique to F. oxysporum, but Six6 is an exception; a homolog is also present in two Colletotrichum spp. SIX6 expression was found to require living host cells and a knockout of SIX6 in F. oxysporum f. sp. lycopersici compromised virulence, classifying it as a genuine effector. Heterologous expression of SIX6 did not affect growth of Agrobacterium tumefaciens in Nicotiana benthamiana leaves or susceptibility of Arabidopsis thaliana toward Verticillium dahliae, Pseudomonas syringae, or F. oxysporum, suggesting a specific function for F. oxysporum f. sp. lycopersici Six6 in the F. oxysporum f. sp. lycopersici- tomato pathosystem. Remarkably, Six6 was found to specifically suppress I-2-mediated cell death (I2CD) upon transient expression in N. benthamiana, whereas it did not compromise the activity of other cell-death-inducing genes. Still, this I2CD suppressing activity of Six6 does not allow the fungus to overcome I-2 resistance in tomato, suggesting that I-2-mediated resistance is independent from cell death.


Assuntos
Proteínas Fúngicas/metabolismo , Fusarium/fisiologia , Regulação Fúngica da Expressão Gênica/fisiologia , Agrobacterium tumefaciens/genética , Agrobacterium tumefaciens/metabolismo , Sequência de Aminoácidos , Arabidopsis/microbiologia , Colletotrichum/genética , Colletotrichum/metabolismo , Proteínas Fúngicas/química , Proteínas Fúngicas/genética , Deleção de Genes , Solanum lycopersicum/microbiologia , Dados de Sequência Molecular , Nicotiana/microbiologia , Verticillium/fisiologia , Virulência
9.
Curr Mol Med ; 13(10): 1591-602, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24206133

RESUMO

Many cancer therapeutics, including radiation therapy, damage DNA eliciting the DNA damage response (DDR). Clinical assays that characterise the DDR could be used to personalise cancer treatment by indicating the extent of damage to tumour and normal tissues and the nature of the cellular response to that damage. The phosphorylated histone γH2AX is generated early in the response to DNA double-strand breaks, the most deleterious form of DNA damage. Translational researchers are developing tissue sampling and assay strategies to apply the measurement of γH2AX to a range of clinical questions, including that of tumour response. The presence of γH2AX is also associated with other cell states including replication stress, hypoxia and apoptosis, which could influence the relationship between γH2AX and clinical endpoints. This review aims to assess the potential of γH2AX as a practical and clinically useful biomarker of tumour and normal tissue responses to therapy.


Assuntos
Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/metabolismo , Diagnóstico por Imagem , Monitoramento de Medicamentos , Histonas/metabolismo , Neoplasias/diagnóstico , Neoplasias/metabolismo , Dano ao DNA , Humanos , Neoplasias/tratamento farmacológico
10.
J Insect Physiol ; 59(4): 487-93, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23439242

RESUMO

Varroa destructor in combination with one or more stressors, such as low food availability or chemical exposure, is considered to be one of the main causes for honey bee colony losses. We examined the interactive effect of pollen availability on the protein content and body weight of young bees that emerged with and without V. destructor infestation. With reduced pollen availability, and the coherent reduced nutritional protein, we expected that V. destructor infestation during the pupal stage would have a larger negative effect on bee development than without infestation. Moreover, when raised with ample pollen available after emergence, infested pupae were expected not to be able to compensate for early losses due to V. destructor. We found that both V. destructor infestation and reduced pollen availability reduced body weight, abdominal protein level, and increased the head to abdomen protein ratio. The availability of pollen did indeed not result in compensation for reduced mass and protein content caused by V. destructor infestation in young bees after 1 week of their adult life. Both V. destructor and nutrition are top concerns for those studying honey bee health and this study demonstrates that both have substantial effects on young bees and that ample available pollen cannot compensate for reduced mass and protein content caused by V. destructor parasitism.


Assuntos
Abelhas/fisiologia , Abelhas/parasitologia , Pólen , Varroidae/fisiologia , Animais , Abelhas/crescimento & desenvolvimento , Feminino , Proteínas/metabolismo , Pupa/crescimento & desenvolvimento , Pupa/parasitologia , Pupa/fisiologia
11.
Cell Death Dis ; 3: e441, 2012 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-23222511

RESUMO

Combined radiochemotherapy is the currently used therapy for locally advanced pancreatic ductal adenocarcinoma (PDAC), but normal tissue toxicity limits its application. Here we test the hypothesis that inhibition of ATR (ATM-Rad3-related) could increase the sensitivity of the cancer cells to radiation or chemotherapy without affecting normal cells. We tested VE-822, an ATR inhibitor, for in vitro and in vivo radiosensitization. Chk1 phosphorylation was used to indicate ATR activity, γH2AX and 53BP1 foci as evidence of DNA damage and Rad51 foci for homologous recombination activity. Sensitivity to radiation (XRT) and gemcitabine was measured with clonogenic assays in vitro and tumor growth delay in vivo. Murine intestinal damage was evaluated after abdominal XRT. VE-822 inhibited ATR in vitro and in vivo. VE-822 decreased maintenance of cell-cycle checkpoints, increased persistent DNA damage and decreased homologous recombination in irradiated cancer cells. VE-822 decreased survival of pancreatic cancer cells but not normal cells in response to XRT or gemcitabine. VE-822 markedly prolonged growth delay of pancreatic cancer xenografts after XRT and gemcitabine-based chemoradiation without augmenting normal cell or tissue toxicity. These findings support ATR inhibition as a promising new approach to improve the therapeutic ration of radiochemotherapy for patients with PDAC.


Assuntos
Proteínas de Ciclo Celular/antagonistas & inibidores , Isoxazóis/administração & dosagem , Neoplasias Pancreáticas/radioterapia , Inibidores de Proteínas Quinases/administração & dosagem , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Pirazinas/administração & dosagem , Radiossensibilizantes/administração & dosagem , Animais , Proteínas Mutadas de Ataxia Telangiectasia , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Quinase 1 do Ponto de Checagem , Dano ao DNA/efeitos dos fármacos , Dano ao DNA/efeitos da radiação , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Fosforilação/efeitos dos fármacos , Fosforilação/efeitos da radiação , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Tolerância a Radiação
12.
Equine Vet J ; 42(6): 547-51, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20716196

RESUMO

REASONS FOR PERFORMING STUDY: The flexion test is used routinely as part of lameness and prepurchase examinations. However, little is known about the mechanisms that cause a positive response to a flexion test. OBJECTIVE: To determine which anatomical regions play a role in a positive outcome of a flexion test of the distal aspect of a forelimb in a nonlame horse. METHODS: Eight clinically sound Dutch Warmblood horses were subjected to a standardised flexion test (force 250 N, time 60 s) inducing a consistent lameness. To discriminate between different areas of the distal aspect of a forelimb, effects of various nerve blocks on the outcome of the flexion test were investigated. Low palmar digital, palmar at the abaxial aspects of the base of the proximal sesamoids, high palmar, ulnar and low 4-point nerve blocks were performed. Flexion test induced lameness was scored before and after each nerve block in separate sessions. RESULTS: The low palmar digital nerve blocks and nerve blocks of the palmar nerves at the abaxial aspect of the base of the proximal sesamoid bones had no significant effect on the flexion test induced lameness score. The ulnar, high palmar and, most dramatically, the low 4-point nerve blocks all caused a significant (P<0.05) reduction in the flexion test induced lameness score. CONCLUSIONS: Anatomical structures (soft tissue nor synovial structures) located distal to the metacarpophalangeal joint appear to contribute only minimally to the outcome of a positive flexion test of the distal aspect of a forelimb in a clinically nonlame horse. The structures in the region of, and including, the metacarpophalangeal joint appear to contribute most to a positive flexion test of the distal aspect of a forelimb in a nonlame horse. POTENTIAL RELEVANCE: The flexion test of the distal aspect of a forelimb may be sensitive for investigating the metacarpophalangeal joint region in horses free from lameness, but may be less relevant for structures distal to this region.


Assuntos
Membro Anterior/anatomia & histologia , Coxeadura Animal/diagnóstico , Exame Físico/veterinária , Animais , Fenômenos Biomecânicos , Cavalos , Bloqueio Nervoso/veterinária , Amplitude de Movimento Articular
14.
Bone ; 44(4): 590-5, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19162254

RESUMO

Osteoporosis (OP) is characterized by low bone mass and weak bone structure, which results in increased fracture risk. It has been suggested that osteoporotic bone is strongly adapted to the main loading direction and less adapted to the other directions. In this study, we hypothesized that osteoporotic femoral heads have 1) an increased anisotropy; 2) a more heterogenic distribution of bone volume fraction (BV/TV) throughout the femoral head; and, 3) a more heterogenic distribution of the trabecular thickness (Tb.Th.) throughout the femoral head, as compared to non-osteoporotic bone. To test these hypotheses, we used 7 osteoporotic femoral heads from patients who fractured their femoral neck and 7 non-fractured femoral heads from patients with osteoarthrosis (OA). Bone structural parameters from the entire trabecular region were analyzed using microCT. We found that the degree of anisotropy was higher in the fractured femoral heads, i.e. 1.72, compared to a value of 1.61 in the non-fractured femoral heads. The BV/TV and Tb.Th. and their variations throughout the femoral head, however, were all significantly lower in the fractured group. Hence, the first hypothesis was confirmed, whereas the other two were rejected. Interestingly, the variation of Tb.Th. throughout the femoral head provided a 100% discrimination between the OP and OA groups, i.e. for the same BV/TV, all fractured cases had a less heterogenic distribution. In conclusion, our results suggest that bone loss in OP takes place uniformly throughout the femoral head, leading to an overall decrease in bone mass and trabecular thickness. Furthermore, the variation of Tb.Th. in the femoral head could be an interesting parameter to improve the prediction of fracture risk in the proximal femur.


Assuntos
Cabeça do Fêmur/diagnóstico por imagem , Cabeça do Fêmur/patologia , Fraturas Ósseas/etiologia , Osteoporose/complicações , Idoso , Idoso de 80 Anos ou mais , Anisotropia , Feminino , Humanos , Valor Preditivo dos Testes , Fatores de Risco , Microtomografia por Raio-X
15.
Vet Radiol Ultrasound ; 48(5): 471-4, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17899985

RESUMO

[123I]-iodo-L-phenylalanine was successfully evaluated for gamma camera imaging in vivo in tumor-bearing athymic mice and in humans with brain tumors. Here, we report the use of this tracer in two dogs with synovial cell sarcoma of the tarsus. [123I]-iodo-L-phenylalanine was quantitatively prepared as a kit formulation using the Cu(1+) +-assisted nucleophilic exchange. Rapid [123I]-2-iodo-L-phenylalanine tumor accumulation was observed with good tumor to background contrast and rapid clearance in these two dogs. This radiopharmaceutical is a promising alternative tumor tracer to overcome the known limitations of 18F-fluorodeoxyglucose and, when labelled with radioiodine-131, has the potential to be used for therapeutic purposes.


Assuntos
Doenças do Cão/diagnóstico por imagem , Radioisótopos do Iodo , Compostos Radiofarmacêuticos , Sarcoma Sinovial/veterinária , Animais , Diagnóstico Diferencial , Cães , Feminino , Fíbula/diagnóstico por imagem , Masculino , Radiografia , Sarcoma Sinovial/diagnóstico por imagem , Tíbia/diagnóstico por imagem , Tomografia Computadorizada de Emissão de Fóton Único/veterinária
16.
S. Afr. fam. pract. (2004, Online) ; 49(1): 1-6, 2007. tab
Artigo em Inglês | AIM (África) | ID: biblio-1269818

RESUMO

"Background: Effective teamwork between doctors and clinical nurse practitioners (CNP) is essential to the provision of quality primary care in the South African context. The Worcester Community Health Centre (CHC) is situated in a large town and offers primary care to the rural Breede Valley Sub-District of the Western Cape. The management of the CHC decided to create dedicated practice teams offering continuity of care; family-orientated care; and the integration of acute and chronic patients. The teams depended on effective collaboration between the doctors and the CNPs.Methods: A co-operative inquiry group; consisting of two facility managers; an administrator; and medical and nursing staff; met over a period of nine months and completed three cycles of planning; action; observation and reflection. The inquiry focused on the question of how more effective teams of doctors and clinical nurse practitioners offering clinical care can be created within a typical CHC.Results: The CHC had established three practice teams; but met with limited success in maintaining the teams over time. The group found that; in order for teams to work; the following are needed: A clear and shared vision and mission amongst the staff. The vision was championed by one or two leaders rather than developed collaboratively by the staff. Continuity of care was supported by the patients and doctors; but the CNPs felt more ambivalent. Family-orientated care within practices met with limited success. Integration of care was hindered by physical infrastructure and the assumptions regarding the care of ""chronics"". Enhanced practitioner-patient relationships were reported by the two teams that had staff consistently available. Significant changes in the behaviour and roles of staff. Some doctors perceived the nurse as an ""assistant"" who could be called on to run errands or perform tasks. Doctors perceived their own role as that of comprehensively managing patients in a consultation; while the CNPs still regarded themselves as nurses who should rotate to other duties and perform a variety of tasks; thus oscillating between the role of practitioner and nurse. The doctors felt responsible for seeing a certain number of patients in the time they were available; while the CNPs felt responsible for getting all the patients through the CHC. The doctors did not create space for mentoring the CNPs; who were often seen as an intrusion and a threat to patient privacy and confidentiality when requesting a consultation. For the CNPs; however; the advantage of practice teams was considered to be greater accessibility to the doctor for joint consultation. The identification of doctors and CNPs with each other as part of a functioning team did not materialise. Effective management of the change process implied the need to ensure sufficient staff were available to allow all teams to function equally throughout the day; to be cognisant of the limitations of the building design; to introduce budgeting that supported semi-autonomous practice teams and to ensure that the staff were provided with ongoing opportunities for dialogue and communication. The implications of change for the whole system should be considered; and not just that for the doctors and nurses.Conclusions: Key lessons learnt included the need to engage with a transformational leadership style; to foster dialogical openness in the planning process and to address differences in understanding of roles and responsibilities between the doctors and the CNPs. The unreliable presence of doctors within the practice team; due to their hospital duties; was a critical factor in the breakdown of the teams.. The CHC plans to further develop practice teams; to learn from the lessons so far and to continue with the co-operative inquiry."


Assuntos
Comportamento Cooperativo , Atenção à Saúde , Hospitais Públicos , Equipe de Enfermagem , Relações Médico-Paciente , Médicos , Atenção Primária à Saúde , Setor Público
17.
Q J Nucl Med Mol Imaging ; 50(3): 155-66, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16868531

RESUMO

AIM: Radiopharmaceuticals can be used to exploit differences between microorganisms in order to distinguish fungal from bacterial infection. Chitin, abundant in the cell wall of fungi, is not present in mammalian or bacterial cells and therefore represents a highly specific target to localize fungal infection. In this study, we have examined the potential of chitin-binding protein (CBP21) from Serratia marcescens as a specific radiotracer for the detection of invasive fungal infections. METHODS: CBP21 was labeled with 99mTc via hydrazinonicotinamide (HYNIC) and its characteristics were analyzed. In vitro binding studies with polymorphic chitin forms and microorganisms (fungi as well as bacteria) were performed. In vivo biodistribution of the compound was studied in immunocompromised mice with bacterial and fungal infections in the left and right thigh muscle, respectively, using 99mTc-HYNIC-myoglobin as size-matched control and 67Ga-citrate as positive control. Scintigraphic images were acquired at 1 and 7 h postinjection of the tracer. RESULTS: 99mTc-HYNIC-CBP21 was labeled with a radiochemical yield of 61% and a specific activity of 22.3 MBq/nmol. Highest in vitro binding percentages were found with beta-chitin (86.8+/-2.4%). Binding interactions to fungi were higher than to bacteria (P<0.05). In vivo, best ratios of fungal infection versus bacterial infection were seen at 5 and 7 h (3.6+/-1.2 and 2.9+/-1.4, respectively) postinjection of the tracer. Maximum uptake of the tracer in fungal infections (0.63+/-0.11%ID/g) at 7 h was significantly (P<0.05) higher than uptake seen in bacterial infections (0.34+/-0.11%ID/g) or the uptake of 99mTc-HYNIC-myoglobin (P<0.05) in the same infections (0.35+/-0.11%ID/g, respectively, 0.3+/-0.01%ID/g). CONCLUSIONS: This study shows that 99mTc-HYNIC-CBP21 is able to specifically interact with chitin in vitro. Scintigraphy and postmortem in vivo data indicate that 99mTc-HYNIC-CBP21 is able to distinguish fungal infection from bacterial infection probably due to a specific interaction of the protein with the chitin in the fungal cell wall.


Assuntos
Infecções Bacterianas/diagnóstico por imagem , Infecções Bacterianas/metabolismo , Proteínas de Bactérias/farmacocinética , Proteínas de Transporte/farmacocinética , Micoses/diagnóstico por imagem , Micoses/metabolismo , Animais , Estudos de Viabilidade , Peptídeos e Proteínas de Sinalização Intracelular , Marcação por Isótopo , Camundongos , Especificidade de Órgãos , Ensaio Radioligante , Cintilografia , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/farmacocinética , Tecnécio/química , Tecnécio/farmacocinética , Distribuição Tecidual
18.
Br J Radiol ; 78(928): 338-42, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15774595

RESUMO

Tumour volume is an important therapeutic endpoint for mouse tumour models in the evaluation of new chemotherapeutic drugs and in pre-clinical evaluation of new radioimmunotherapy pharmaceuticals. In this study, two 1 T MRI-based methods both using T1-T2 hybrid weighting, a manual method (determination of the area per slice) and a semi-automated method (using thresholding), are compared with two classical methods, the abovementioned calliper method and volumetry by water displacement after dissection of the tumour. Interoperator and intraoperator differences for both MRI-based methods were good (no differences p<0.05 using a repeated measures analysis of variance (ANOVA) test). Correlation between the different methods was excellent. No significant differences were obtained (p<0.05), except for the semi-automated method, because it automatically excludes necrotic regions from the tumour. Therefore, we conclude that both manual and semi-automated tumour volumetry in subcutaneous tumour bearing athymic mice by low-field MRI are accurate and reliable methods. The semi-automated method is especially useful for larger tumour volumes, since it accounts for necrotic areas within the tumour.


Assuntos
Imageamento por Ressonância Magnética/métodos , Neoplasias/diagnóstico , Animais , Imageamento Tridimensional , Masculino , Camundongos , Camundongos Nus
19.
Mol Plant Microbe Interact ; 18(1): 15-23, 2005 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15672814

RESUMO

I-3-Mediated resistance of tomato against Fusarium wilt disease caused by Fusarium oxysporum f. sp. lycopersici depends on Six1, a protein that is secreted by the fungus during colonization of the xylem. Among natural isolates of F. oxysporum f. sp. lycopersici are several that are virulent on a tomato line carrying only the I-3 resistance gene. However, evasion of I-3-mediated resistance by these isolates is not correlated with mutation of the SIX1 gene. Moreover, the SIX1 gene of an I-3-virulent isolate was shown to be fully functional in that i) the gene product is secreted in xylem sap, ii) deletion leads to a further increase in virulence on the I-3 line as well as reduced virulence on susceptible lines, and iii) the gene confers full avirulence on the I-3 line when transferred to another genetic background. Remarkably, all I-3-virulent isolates were of race 1, suggesting a link between the presence of AVR1 and evasion of I-3-mediated resistance.


Assuntos
Fusarium/patogenicidade , Solanum lycopersicum/genética , Solanum lycopersicum/microbiologia , Proteínas Fúngicas/genética , Fusarium/genética , Genes de Plantas/fisiologia , Imunidade Inata/genética , Filogenia , Doenças das Plantas/microbiologia , Virulência/genética
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