Biomedical subjects

Simon Robinson

Publications and source records attributed to Simon Robinson.

17 recordsLinked to original sources

PubMed2005

Noninvasive targeted imaging of matrix metalloproteinase activation in a murine model of postinfarction remodeling.

BACKGROUND: Time-dependent activation of matrix metalloproteinases (MMPs) after myocardial infarction (MI) contributes to adverse left ventricular (LV) remodeling; however, noninvasive methods to monitor this process serially are needed. METHODS AND RESULTS: MMP-targeted radiotracers were developed that displayed selective binding kinetics to the active MMP catalytic domain. Initial nonimaging studies were performed with a (111)In-labeled MMP-targeted radiotracer ((111)In-RP782) and negative control compound ((111)In-RP788) in control mice (Ctrl) and in mice 1 week after surgically induced MI. Localization of (111)In-RP782 was demonstrated within the MI by microautoradiography. A 334+/-44% increase (P<0.001 versus Ctrl) in relative retention of (111)In-RP782 was confirmed by gamma well counting of myocardium. Subsequent high-resolution dual-isotope planar and hybrid micro-single-photon emission computed tomography/CT imaging studies with an analogous 99mTc-labeled MMP-targeted radiotracer (99mTc-RP805) and 201Tl demonstrated favorable biodistribution and clearance kinetics of 99mTc-RP805 for in vivo cardiac imaging, with robust retention 1 to 3 weeks after MI in regions of decreased 201Tl perfusion. Gamma well counting yielded a similar approximately 300% increase in relative myocardial retention of 99mTc-RP805 in MI regions (Ctrl, 102+/-9%; 1 week, 351+/-77%; 2 weeks, 291+/-45%; 3 weeks, 292+/-41%; P<0.05 versus Ctrl). Myocardial uptake in the MI region was also significantly increased approximately 5-fold when expressed as percentage injected dose per gram tissue. There was also a significant 2-fold increase in myocardial activity in remote regions relative to control mice, suggesting activation of MMPs in regions remote from the MI. CONCLUSIONS: This novel noninvasive targeted MMP radiotracer imaging approach holds significant diagnostic potential for in vivo localization of MMP activation and tracking of MMP-mediated post-MI remodeling.

Animals↗

PubMed2005

A comparison of PET imaging characteristics of various copper radioisotopes.

PURPOSE: PET radiotracers which incorporate longer-lived radionuclides enable biological processes to be studied over many hours, at centres remote from a cyclotron. This paper examines the radioisotope characteristics, imaging performance, radiation dosimetry and production modes of the four copper radioisotopes, ( 60)Cu,( 61)Cu,( 62)Cu and( 64)Cu, to assess their merits for different PET imaging applications. METHODS: Spatial resolution, sensitivity, scatter fraction and noise-equivalent count rate (NEC) are predicted for( 60)Cu,( 61)Cu,( 62)Cu and( 64)Cu using a model incorporating radionuclide decay properties and scanner parameters for the GE Advance scanner. Dosimetry for( 60)Cu,( 61)Cu and( 64)Cu is performed using the MIRD model and published biodistribution data for copper(II) pyruvaldehyde bis(N(4)-methyl)thiosemicarbazone (Cu-PTSM). RESULTS: (60)Cu and( 62)Cu are characterised by shorter half-lives and higher sensitivity and NEC, making them more suitable for studying the faster kinetics of small molecules, such as Cu-PTSM.( 61)Cu and( 64)Cu have longer half-lives, enabling studies of the slower kinetics of cells and peptides and prolonged imaging to compensate for lower sensitivity, together with better spatial resolution, which partially compensates for loss of image contrast.( 61)Cu-PTSM and( 64)Cu-PTSM are associated with radiation doses similar to [(18)F]-fluorodeoxyglucose, whilst the doses for( 60)Cu-PTSM and( 62)Cu-PTSM are lower and more comparable with H(2) (15)O. CONCLUSION: The physical and radiochemical characteristics of the four copper isotopes make each more suited to some imaging tasks than others. The results presented here assist in selecting the preferred radioisotope for a given imaging application, and illustrate a strategy which can be extended to the majority of novel PET tracers.

Computer Simulation↗

PubMed2005

The selection of intended actions and the observation of others' actions: a time-resolved fMRI study.

Whenever we plan, imagine, or observe an action, the motor systems that would be involved in preparing and executing that action are similarly engaged. The way in which such common motor activation is formed, however, is likely to differ depending on whether it arises from our own intentional selection of action or from the observation of another's action. In this study, we use time-resolved event-related functional MRI to tease apart neural processes specifically related to the processing of observed actions, the selection of our own intended actions, the preparation for movement, and motor response execution. Participants observed a finger gesture movement or a cue indicating they should select their own finger gesture to perform, followed by a 5-s delay period; participants then performed the observed or self-selected action. During the preparation and readiness for action, prior to initiation, we found activation in a common network of higher motor areas, including dorsal and ventral premotor areas and the pre-supplementary motor area (pre-SMA); the more caudal SMA showed greater activation during movement execution. Importantly, the route to this common motor activation differed depending on whether participants freely selected the actions to perform or whether they observed the actions performed by another person. Observation of action specifically involved activation of inferior and superior parietal regions, reflecting involvement of the dorsal visual pathway in visuomotor processing required for planning the action. In contrast, the selection of action specifically involved the dorsal lateral prefrontal and anterior cingulate cortex, reflecting the role of these prefrontal areas in attentional selection and guiding the selection of responses.

Adult↗

PubMed2005

Role of inflammation in cardiopulmonary health effects of PM.

The relationship between increased exposure to PM and adverse cardiovascular effects is well documented in epidemiological studies. Inflammation in the lungs, caused by deposited particles, can be seen as a key process that could mediate adverse effects on the cardiovascular system. There are at least three potential pathways that could lead from pulmonary inflammation to adverse cardiovascular effects. Firstly, inflammation in the lung could lead to systemic inflammation, which is well known to be linked to sudden death from cardiovascular causes. Systemic inflammation can lead to destabilization by activation of inflammatory processes in atheromatous plaques. Secondly, inflammation can cause an imbalance in coagulation factors that favor propagation of thrombi if thrombosis is initiated. Thirdly, inflammation could affect the autonomic nervous system activity in ways that could lead to alterations in the control of heart rhythm which could culminate in fatal dysrhythmia.

Air Pollutants↗

PubMed2005

Prevalence of pus in radiologically diseased sinuses in patients undergoing surgery for chronic rhinosinusitis.

OBJECTIVE: To establish the prevalence of pus in radiologically diseased sinuses in patients undergoing sinus surgery and to correlate this with the bacterial load in the sinuses. STUDY DESIGN AND SETTING: A prospective study performed on adult patients with the diagnosis of chronic sinusitis undergoing endoscopic sinus surgery at an Adelaide group of academic hospitals. In 45 consecutive and unselected patients, a radiologically diseased sinus was surgically opened, and a specially designed suction aspirator was placed into the sinus under endoscopic control. These aspirates were Gram stained and cultured to quantify the polymorphonuclear neutrophil count, bacterial flora, and bacterial colony count. The CT scans of all patients were graded by using the Lund-Mackay scoring system. RESULTS: A variety of bacteria, most commonly staphylococci, were cultured from a radiologically diseased sinus in 88% of patients. There was no correlation between the bacterial colony count and presence of pus, and only 11% of patients had microscopic evidence of inflammation in sinus aspirates. There was no correlation between the Lund-Mackay CT score and the presence of pus in the sinus. CONCLUSIONS: The majority of patients undergoing surgery for chronic sinusitis did not have a purulent exudate, and there was no correlation with the bacterial load. The usefulness of antibiotics in the treatment of chronic rhinosinusitis, in the absence of macroscopic pus, is questionable.

Adult↗

PubMed2005

Murine mammary adenocarcinoma cells transfected with p53 and/or Flt3L induce antitumor immune responses.

Transfection of tumors with tumor-associated antigens (Ags) or cytokines can increase immunogenicity and slow down tumor growth. However, the effect of cotransfection with genes that encode a tumor-associated Ag, such as the tumor suppressor gene p53, and a cytokine has been rarely investigated. We report that transfection of 4T1 mammary tumor cells (p53-null) with the dendritic cell (DC) growth factor, fms-like tyrosine kinase 3 ligand (Flt3L), significantly delayed their growth in vivo, resulting in the rejection of 100% of the tumors formed by injection of tumor cells cotransfected with Flt3L and p53. Immunization with irradiated 4T1 cells transfected with Flt3L induced DC infiltration of the immunization site and significantly increased the antitumor T-cell responses. Further, immunization with irradiated 4T1 cells cotransfected with p53 and Flt3L significantly increased p53-specific immune responses, as compared to vaccination with 4T1 cells transfected with either Flt3L or p53 alone. These responses included increased activity against clone 66 (Cl-66), a sister tumor to 4T1 with high murine mutant p53 expression levels. Challenge with Cl-66 revealed that immunization with irradiated 4T1-Flt3L-p53 cells significantly slowed growth, prolonged survival, and resulted in complete remissions. Further, immunization with irradiated 4T1-Flt3L also slowed Cl-66 growth, although to a lesser extent than 4T1-Flt3L-p53. We suggest that immunization with DCs transfected with the Flt3L transgene and a tumor Ag may potentially heighten T-cell responses and therapeutic activity.

Adenocarcinoma↗

PubMed2005

Canine fossa puncture and clearance of the maxillary sinus for the severely diseased maxillary sinus.

OBJECTIVES: To assess the impact of canine fossa puncture (CFP) with clearance of the maxillary sinus during endoscopic sinus surgery on the subjective and objective outcomes as defined by quality of life questionnaires, endoscopic findings, endoscopic aspirate for culture and sensitivity, and magnetic resonance imaging (MRI) evaluation. STUDY DESIGN: Retrospective, cross-sectional study. METHODS: Twenty-five patients who had undergone canine fossa were compared to 12 patients who had undergone routine endoscopic middle meatal clearance of the maxillary sinus. At an average postoperative time point of 19.9 months, all patients were administered the chronic sinusitis survey (CSS) and a visual analogue scale (VAS). At this visit, patients underwent nasendoscopy, sampling of the ostial region for bacterial and fungal cultures, and MRI of the sinuses. RESULTS: There were 42 sides for analysis from 25 patients on the study arm; the control arm comprised 12 patients with completely opacified maxillary sinuses and 17 sides for analysis. The CSS symptom subscore was better in the CFP group (Mann-Whitney test, P = .02). The overall VAS score was less in the CFP group (Mann-Whitney test, P = .01), indicating better symptom control. No opacification was evident in 61.9% of patients in the CFP group compared with 11.8% in the control arm (chi, P < .001). CONCLUSION: CFP is a useful technique to address the severely diseased maxillary sinus and is associated with significantly better symptom control compared with the transnasal middle meatal antrostomy clearance of the maxillary sinus.

Adult↗

PubMed2005

Endoscopic management of benign tumors extending into the infratemporal fossa: a two-surgeon transnasal approach.

OBJECTIVES/HYPOTHESIS: Preliminary results of the endoscopic two-surgeon technique for the management of benign infratemporal fossa tumors are presented. METHODS: Four patients with juvenile nasopharyngeal angiofibroma, a patient with an inverting papilloma, and a patient with a maxillary nerve schwannoma were reviewed. The average age was 22.7 years; the male-to-female ratio was 5:1. The endoscopic anatomy and surgical technique are presented. RESULTS: The two-surgeon technique allowed complete resection of all six tumors extending into the infratemporal fossa. There has been no recurrence of tumor within the infratemporal fossa, after a mean follow-up of 31.3 months (SD = 11.2 mo). CONCLUSION: The two-surgeon transnasal technique allows benign infratemporal fossa tumors to be resected endoscopically.

Adolescent↗

PubMed2005

Patterns of innervation of the anterior maxilla: a cadaver study with relevance to canine fossa puncture of the maxillary sinus.

OBJECTIVES/HYPOTHESIS: Complications from canine fossa puncture of the maxillary sinus are caused by damage to the anterior superior alveolar nerve (ASAN) and the middle superior alveolar nerve (MSAN). The aim of this study was to elucidate the pattern of ASAN and MSAN within the anterior maxilla and to secondly determine suitable surgical landmarks to aid in accurately localizing the area of the canine fossa least likely to produce complications when a trocar is passed into the maxillary sinus. METHODS: Anatomic dissection of the anterior face of the maxilla from 20 cadaver heads was performed. The pattern and presence of the ASAN and MSAN was identified on each side and tabulated. Landmarks for the safest entry point for canine fossa puncture were determined, and each side had a puncture placed using these landmarks. Any disruption of nerves was noted. RESULTS: Multiple differing patterns of ASAN were identified. The ASAN emerged from its foramen as a single trunk in 30 (75%) sides and in a double trunk in 10 (25%). In 24 (60%), single or multiple branches from the ASAN trunks were identified. A MSAN was identified in 9 (23%) maxillae. The safest entry point for a canine fossa puncture was where a vertical line drawn through the mid-pupillary line was bisected by a horizontal line drawn through the floor of the pyriform aperture. CONCLUSIONS: There is significant variation in the pattern of ASAN and MSAN within the anterior face of the maxilla. By using the newly described landmarks when performing a canine fossa puncture, there is reduced risk of damage to these nerves and provides a reliable point to enter the maxillary sinus.

Cadaver↗

PubMed2004

Robust field map generation using a triple-echo acquisition.

PURPOSE: To establish a fast and robust technique for generating magnetic field maps for the correction of geometric distortions in echo-planar magnetic resonance (MR) images. MATERIALS AND METHODS: Multislice gradient-echo (GE) images were acquired at echo times of 6, 6.5, and 7.5 msec in order to cover a field shift range of +/-666 Hz in the resulting B0 maps. To account for possible phase wrap scenarios, seven phase triples were calculated for each pixel. Linear regression of the phase vs. echo time was performed for each set. The slope of the set with the minimum fitting error was taken as the true magnetic field in the respective pixel. RESULTS: Based on the fitting error distribution, the technique is shown to be feasible and effective for assessing the field distribution in the brain at 3 T, especially in inferior brain areas (amygdalae, hippocampus). Examples of echo-planar images distortion corrected using the calculated field maps are shown. CONCLUSION: The approach presented yields robust estimation of magnetic field maps and requires under a minute of additional acquisition time and only seconds of computational time. As such, it is easily possible to apply image distortion correction in routine functional MR imaging (fMRI) studies, enabling improved coregistration of brain activation maps with structures on anatomical images.

Algorithms↗

PubMed2004

The effect of nasal packing and prednisolone on mucosal healing and reciliation in a sheep model.

STATEMENT OF PROBLEMS: To determine whether topical prednisolone affected sinus mucosal healing in a sheep animal model. METHODS OF STUDY: A standardised sheep model with concurrent Oestrus ovus infection was utilised. Following full thickness nasal mucosal injuries, hyaluronic acid packs soaked with prednisolone were applied to one side of the nasal cavity, with hyaluronic acid packs without prednisolone, to the other. At four weekly intervals, for 16 weeks, mucosal biopsies were taken and analysed for epithelial thickness and length, for cilial height and percentage of ciliated mucosa and mucosal inflammation. RESULTS: Eighteen sheep were utilised, with each acting as its own control. At completion of the study there was no statistical difference between the control or treatment group for the percentage of mucosal epithelialisation (mean: 86.5% vs 92.2%), epithelial thickness (mean: 39.7 microns vs 39.3 microns or the percentage of epithelium ciliated (mean: 26.5% vs 30.8%). Furthermore prednisolone had no effect on mucosal inflammation with the control arm mean score of 3.44 (SD .022) and treatment arm mean of 3.77 (SD 0.21). CONCLUSION: Hyaluronic acid nasal packs soaked in prednisolone failed to improve the speed of mucosal healing or re-ciliation in the sheep model of eosinophilic rhinosinusitis.

Adjuvants, Immunologic↗

PubMed2004

Tele-homecare for chronically ill persons: pilot trials, medical outcomes and future perspectives.

Socio-economic trends including the ageing of populations in the developed world have let to markedly increased interest in improving society's ability to deliver effective care to older and chronically ill patients at home. The paper reports progress from recent European research on three key fronts faced in the diffusion of tele-homecare: Pilot applications to explore the features of as yet untried care domains, full clinical trials to present hard evidence of desired medical outcomes, and R&D to expand the capability of tele-homecare systems to meet the needs of a yet wider variety of chronic illnesses and patient groups.

Aging↗

PubMed2003

Regional, but not systemic recruitment/expansion of dendritic cells by a pluronic-formulated Flt3-ligand plasmid with vaccine adjuvant activity.

Regional recruitment of dendritic cells (DCs) by the local administration of granulocyte macrophage-colony stimulating factor (GM-CSF) or Flt3-ligand (Flt3L) has vaccine adjuvant activity. However, Flt3L, with its DC growth factor activity, has not been extensively studied as a vaccine adjuvant, particularly as a plasmid vector. We report that the intramuscular (IM) injection of a Flt3L plasmid (pNGVL-hFlex), when formulated in a pluronic carrier (SP1017, Supratek Pharma, Inc., Laval, Que., Canada), recruits DC to the injection site and regional lymph nodes (LNs) and augments immune responses to a p17 HIV plasmid vaccine to a greater extent than the injection of a naked DNA vaccine alone. Following IM administration of pNGVL-hFlex, Flt3L mRNA, Flt3L protein and infiltrating DC accumulate at the injection site. The number of DC in the draining LNs are also significantly increased with the greatest increase observed following injection of 2.5 microg of pNGVL-hFlex formulated in 0.01% SP1017. Flow cytometric studies demonstrate that the LN-infiltrating DC is mainly of the CD11c(+)CD11b(-) phenotype (IL-12 producing). Further, the co-injection of pNGVL3-hFlex and p17 HIV plasmids, formulated in SP1017, significantly increases the immune responses to the plasmid vaccine (pVAX-gag). The co-injection of pVAX-gag and pNGVL3-hFlex, formulated in SP1017, significantly increase delayed-type hypersensitivity responses and the numbers of antigen (Ag)-specific interferon-gamma secreting T cells in the spleen (Enzyme Linked Immune Spot (ELISpot) assay), compared to mice immunized with pVAX-gag formulated in SP1017 alone. We conclude that the IM injection of pNGVL-hFlex with SP1017 can increase the number of DC in draining LN and at the site of injection, thereby providing adjuvant activity for a plasmid vaccine resulting in a significantly increased, Ag-specific T cell response.

Adjuvants, Immunologic↗

PubMed2003

Radiation dose to abdominal organs of the mouse due to 90Y in the urinary bladder.

Radiation dosimetry estimates in mice have proven useful in evaluating therapeutic radiopharmaceuticals. Current models for mice do not take into account the dose to abdominal organs from radioactivity in the urinary bladder. Although the dose from this source is probably low for slowly clearing compounds such as antibodies, it may be considerable for small molecule (90)Y conjugates undergoing rapid renal clearance. To evaluate this possibility, we modeled the mouse bladder as a 6 mm sphere, surrounded by a 0.5 mm thick shell. We then calculated the radiation dose that might be received by the shell and by more distant points, using the point kernel method with the Loevinger analytical point kernel. A Monte Carlo calculation using EGS4 was also performed. Surface dose calculations were compared with in vitro experimental data. LiF TLD dosimeters were placed directly under five separated, flat-bottomed, 6-mm diameter wells containing (90)Y on a 96-well plate. Dose versus distance from the mouse urinary bladder was calculated using kinetic data from imaging studies of a renally cleared (111)In analog compound currently under investigation. From this, it was estimated that whole body administration of 34.8 MBq of the (90)Y analog compound would yield a bladder wall dose estimate of approximately 98 Gy. Structures within 2 mm of the bladder would receive additional estimated doses of at least 15 Gy. This radiation dose approaches that which is known from external beam data to cause fibrosis in mice. Because of the greater size of the human bladder compared with that of the mouse relative to the range of (90)Y beta particles, the radiation exposure from the same residence time in man was estimated to be considerably lower. This highlights a potential practical limitation of extrapolating radiotoxicity findings in the mouse to human subjects.

Abdomen↗

PubMed2003

Design, synthesis, and evaluation of radiolabeled integrin alpha v beta 3 receptor antagonists for tumor imaging and radiotherapy.

The goal of this research is the development of tumor imaging and radiotherapeutic agents based on targeting of the integrin alpha(v)beta(3) (vitronectin receptor). Macrocyclic chelator DOTA has been conjugated to peptidomimetic vitronectin receptor antagonist SH066 to give TA138. TA138 and (89)Y-TA138 retain antagonist properties and high affinity for integrin alpha(v)beta(3) (IC(50) = 12 and 18 nM, respectively), and good selectivity versus integrin alpha(IIb)beta(3) (IC(50) > 10,000 nM). TA138 forms stable complexes with (111)In and (90)Y in > 95% RCP. (111)In-TA138 demonstrates high tumor uptake in the c-neu Oncomouse (Charles River Laboratories [Charles River, Canada]) mammary adenocarcinoma model (9.39% ID/g at 2 hours PI) and low background activity. Blood clearance is rapid and excretion is renal. Tumors are visible as early as 0.5 hours PI. Radiotherapy studies in the c-neu Oncomouse model demonstrated a slowing of tumor growth at a dose of 15 mCi/m(2), and a regression of tumors at a dose of 90 mCi/m(2).

Adenocarcinoma↗

PubMed2002

'Tender loving care' as a relational ethic in nursing practice.

In the West, the term 'tender, loving care' (TLC) has traditionally been used as a defining term that characterizes nursing. When this expression informs practice, it can comfort the human spirit at times of fear and vulnerability. Such notions offer meaning and resonance to the 'lived experience' of giving and receiving care. This suggests that, in a nursing context, TLC is rooted firmly in relationship, that is, the dynamic that exists between carer and cared for. Despite this emphasis on relationship, there is a scarcity of literature that draws a connection between TLC and the moral challenge that is so much a part of human interaction. In this article we will address this deficit and present a narrative that places TLC at the centre of moral engagement between nurse and patient; in essence, we offer an alternative means of viewing relational ethics.

Empathy↗

PubMedDate not supplied

An evaluation of effect of pterygopalatine fossa injection with local anesthetic and adrenalin in the control of nasal bleeding during endoscopic sinus surgery.

BACKGROUND: The aim of this study was to determine the effect of pterygopalatine fossa infiltration with lidocaine and adrenalin on bleeding in the surgical field during endoscopic sinus surgery. METHODS: A prospective blind randomized controlled trial was performed. Fifty-five patients were randomized to receive a unilateral transoral infiltration of the pterygopalatine fossa with 2 mL of 2% lidocaine and 1:80,000 adrenalin. The operating surgeon was blinded as to which side had been infiltrated at the start of surgery. The surgical field was graded on a previously validated surgical field grading scale every 15 minutes with the side being operated on alternated every 30 minutes. The pulse, mean arterial blood pressure, and end-tidal CO2 concentration were monitored with each surgical field observation. RESULTS: At each individual time point from 30 minutes to 3.5 hours there was a significant difference in surgical grade between injected and noninjected sides in favor of the injected side (p = 0.01). The difference between surgical grades averaged across all time points was slight but significant. The injected side had an overall mean of 2.59 (SE, 0.22) compared with 2.99 (SE, 0.23) for the noninjected side. Heart rate also was found to correlate independently to surgical grade. CONCLUSION: Injection of the pterygopalatine fossa resulted in an improved surgical field during endoscopic sinus surgery.

Adult↗