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Biomedical subjects

Gary Cook

Publications and source records attributed to Gary Cook.

16 recordsLinked to original sources

Self-activated liquid-crystal cells with photovoltaic substrates.

We show that photovoltaic fields are capable of efficiently reorienting liquid crystals, leading to new concepts of optically addressable light modulators. Using an arrangement consisting of a liquid-crystal layer between LiNbO3:Fe photovoltaic substrates, we observed spatial filtering due to self-phase modulation in a planar-oriented cell and nonlinear transmission between crossed polarizers in a twist-oriented cell. These processes do not require an external electric field. The substrates are arranged such that light propagates along the +c axis in each substrate, allowing a secondary process of power transfer to occur through contradirectional photorefractive two-beam coupling.

Journal Article↗

Readmission after hysterectomy and prophylactic low molecular weight heparin: retrospective case-control study.

OBJECTIVE: To determine whether use of tinzaparin, a low molecular weight heparin introduced for prophylactic management of deep vein thrombosis, increases the risk of serious postoperative bleeding leading to a higher than expected 28 day readmission rate after discharge for hysterectomy. DESIGN: Retrospective case-control study using computerised hospital inpatient data and review of case notes. SETTING: District general hospital. SUBJECTS: 2108 patients undergoing hysterectomy between August 1997 and March 2003 MAIN OUTCOME MEASURES: Readmission and reoperation associated with bleeding. RESULTS: 54 cases of serious postoperative bleeding were identified, 46 of which were readmissions. These 54 cases were compared with 179 controls. Regression analysis indicated a positive relation between prophylaxis with tinzaparin and serious postoperative bleeding. There was a significant twofold increase in odds (odds ratio 2.02, 95% confidence interval 1.02 to 4.05) after adjustment for type of operation, age, and type of pain relief. CONCLUSIONS: In the prophylactic treatment of thromboembolic disease after hysterectomy, compared with calci-heparin, tinzaperin is associated with a twofold increase in risk of serious postoperative bleeding.

Adult↗

Preparation and use of 131I magic gel as a dosimeter for targeted radionuclide therapy.

Clinical interest in targeted radiotherapy is increasing, but accurate dosimetry studies are difficult to achieve. The aim of this study was to investigate the preparation and use of a "normoxic" polymer gel (with a tissue-equivalent density), known as MAGIC gel, and magnetic resonance imaging (MRI) for nonsealed source dosimetry. MAGIC gel samples were mixed with deionized water (MAGIC95) or a solution of 131I (131I-MAGIC95). By measuring the radioinduced variations of R2 values (relaxivity) of irradiated gels, we analyzed the response of MAGIC95 and MAGIC samples to external photon beam or 131I irradiation (131I-MAGIC95). MRI showed that a homogeneous dose distribution from 131I can be achieved if the MAGIC gel, at a temperature of approximately 35 degrees C, is mixed in 131I solution and the resulting mixture shaken gently for 30 minutes. It is important that the vials are completely filled, as residual air reduces polymerization and causes spontaneous polymerization stripes. Responses of MAGIC95 or MAGIC gels to external photon beam irradiation are similar. The variations of R2 values for 131I-MAGIC95 gel depend on the absorbed dose and not on the duration of the irradiation being reproducible from one batch of gel to another. MAGIC gel responses to 131I or external beam irradiation (EBI) are different. Our preliminary results suggest that radiolabeled "normoxic" polymer can be easily and safely produced. Radiolabeled MAGIC gel may, therefore, be suitable for the creation of phantoms dedicated to nonsealed source dosimetry.

Ascorbic Acid↗

Tumor targeting by an aptamer.

UNLABELLED: Aptamers are small oligonucleotides that are selected to bind tightly and specifically to a target molecule. We sought to determine whether aptamers have potential for in vivo delivery of radioisotopes or cytotoxic agents. METHODS: TTA1, an aptamer to the extracellular matrix protein tenascin-C, was prepared in fluorescent and radiolabeled forms. After in vivo administration, uptake and tumor distribution of Rhodamine Red-X-labeled aptamer was studied by fluorescence microscopy. In glioblastoma (U251) and breast cancer (MDA-MB-435) tumor xenografts, biodistribution and imaging studies were performed using TTA1 radiolabeled with (99m)Tc. Tenascin-C levels and tumor uptake were studied in a variety of additional human tumor xenografts. To assess the effect of radiometal chelate on biodistribution, mercapto-acetyl diglycine (MAG(2)) was compared with diethylenetriaminepentaacetic acid and with MAG(2)-3,400-molecular-weight PEG (PEG(3,400)). RESULTS: Intravenous injection of fluorescent aptamer TTA1 produced bright perivascular fluorescence in a xenografted human tumor within 10 min. In the ensuing 3 h, fluorescence diffused throughout the tumor. Labeled with (99m)Tc, TTA1 displayed rapid blood clearance, a half-life of less than 2 min, and rapid tumor penetration: 6% injected dose (%ID)/g at 10 min. Tumor retention was durable, with 2.7 %ID/g at 60 min and a long-lived phase that stabilized at 1 %ID/g. Rapid tumor uptake and blood clearance yielded a tumor-to-blood ratio of 50 within 3 h. Both renal and hepatic clearance pathways were observed. Using the (99m)Tc-labeled aptamer, images of glioblastoma and breast tumors were obtained by planar scintigraphy. Aptamer uptake, seen in several different human tumors, required the presence of the target protein, human tenascin-C. Modification of the MAG(2) radiometal chelator dramatically altered the uptake and clearance patterns. CONCLUSION: TTA1 is taken up by a variety of solid tumors including breast, glioblastoma, lung, and colon. Rapid uptake by tumors and rapid clearance from the blood and other nontarget tissues enables clear tumor imaging. As synthetic molecules, aptamers are readily modified in a site-specific manner. A variety of aptamer conjugates accumulate in tumors, suggesting imaging and potentially therapeutic applications.

Animals↗

Spatial distribution of power coupling in self-pumped photorefractive reflection gratings.

The spatial distribution of the power transfer achieved by contradirectional two-beam coupling using self-pumped photorefractive reflection gratings is investigated in two materials with different photorefractive gain coefficients, LiNbO3:Fe and KNbO3:Fe. Incremental portions of the volume grating are erased optically by inducing thin optical damage planes, reducing the overall two-beam coupling efficiency. By monitoring the effect of local grating disruption, the distribution of power transfer is spatially resolved throughout the crystal, and the results are found to be in agreement with our theoretical predictions.

Journal Article↗

The incorporation of SPECT functional lung imaging into inverse radiotherapy planning for non-small cell lung cancer.

BACKGROUND AND PURPOSE: Patients with non-small cell lung cancer (NSCLC) often have inhomogeneous lung perfusion. Radiotherapy planning computed tomography (CT) scans have been accurately co-registered with lung perfusion single photon emission computed tomography (SPECT) scans to design radiotherapy treatments which limit dose to healthy 'perfused' lung. PATIENTS AND METHODS: Patients with localised NSCLC had CT and SPECT scans accurately co-registered in the planning system. The SPECT images were used to define a volume of perfused 'functioning' lung (FL). Inverse planning software was used to create 3D-conformal plans, the planning objective being either to minimise the dose to whole lungs (WL) or to minimise the dose to FL. RESULTS: Four plans were created for each of six patients. The mean difference in volume between WL and FL was 1011.7 cm(3) (range 596.2-1581.1cm(3)). One patient with bilateral upper lobe perfusion deficits had a 16% reduction in FLV(20) (the percentage volume of functioning lung receiving >or=20 Gy). The remaining patients had inhomogeneous perfusion deficits such that inverse planning was not able to sufficiently optimise beam angles to avoid functioning lung. CONCLUSION: SPECT perfusion images can be accurately co-registered with radiotherapy planning CT scans and may be helpful in creating treatment plans for patients with large perfusion deficits.

Carcinoma, Non-Small-Cell Lung↗

Positron emission tomography for target volume definition in the treatment of non-small cell lung cancer.

The additional benefit of positron emission tomography (PET) in the initial staging of non-small cell lung cancer (NSCLC) has generated interest in 18F-fluorodeoxyglucose (FDG) PET as a means of defining the extent of primary lung tumour for radiotherapy treatment planning (RTP). A review of published data suggests that PET results in a reduction in the CT-derived GTV for NSCLC primary target volume in 15% of the patients. This is principally due to the ability of PET to distinguish tumour from atelectasis. However, the difficulty of tumour edge definition, limited spatial resolution and tumour motion during image acquisition currently limits the accuracy of PET in target volume delineation in NSCLC without adjacent lung consolidation. This is compounded by the lack of data correlating PET with spatial pathology at the primary tumour site. With the current technical limitations, it is not established that PET can add accuracy to the CT-defined primary target delineation in RTP of NSCLC. It is hoped that advances in PET and combined PET/CT imaging may overcome some of the technical limitations. Future use of PET for primary tumour delineation in NSCLC will also be critically dependent on the detailed studies of imaging-pathology correlation.

Carcinoma, Non-Small-Cell Lung↗

Positron emission tomography and bone metastases.

The use of 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in the evaluation and management of patients with malignancy continues to increase. However, its role in the identification of bone metastases is far from clear. FDG has the advantage of demonstrating all metastatic sites, and in the skeleton it is assumed that its uptake is directly into tumor cells. It is probable that for breast and lung carcinoma, FDG-PET has similar sensitivity, although poorer specificity, when compared with the isotope bone scan, although there is conflicting evidence, with several articles suggesting that it is less sensitive than conventional imaging in breast cancer. There is convincing evidence that for prostate cancer, FDG-PET is less sensitive than the bone scan and this may be tumor specific. There is very little data relating to lymphoma, but FDG-PET seems to perform better than the bone scan. There is an increasing body of evidence relating to the valuable role of FDG-PET in myeloma, where it is clearly better than the bone scan, presumably because FDG is identifying marrow-based disease at an early stage. There are, however, several other important variables that should be considered. The morphology of the metastasis itself appears to be relevant. At least in breast cancer, different patterns of FDG uptake have been shown in sclerotic, lytic, or lesions with a mixed pattern, Furthermore, the precise localization of a metastasis in the skeleton may be important with regard to the extent of the metabolic response induced. Previous treatment is highly relevant and it has been found that although the majority of untreated bone metastases are positive on PET scans and have a lytic pattern on computed tomography (CT), after treatment, incongruent CT-positive/PET-negative lesions are significantly more prevalent and generally are blastic, which presumably reflects a direct effect of treatment. Finally, the aggressiveness of the tumor itself may be relevant. The most important question, however, is irrespective of whether a lesion is seen on x-ray, CT, or bone scan and irrespective of lytic of blastic morphology: if the FDG-PET study is negative, what is the clinical relevance of that lesion?

Bone Neoplasms↗

Metastatic thyroid carcinoma causing superior vena caval obstruction diagnosed on I-131 scan.

An 80-year-old woman was referred for a painless mass arising in right side of her neck of 4 months' duration. Ultrasound revealed a multinodular goiter, but cytology confirmed a follicular carcinoma. Thyroid function was normal. Total thyroidectomy was performed with evidence of tumor infiltration into the strap muscles extending up to the right submandibular gland and right internal jugular vein, which was completely occluded. Radioiodine was considered as the treatment of choice postoperatively. This is an unusual case of SVC obstruction caused by tumor embolus diagnosed on I-131 scan.

Adenocarcinoma, Follicular↗

Dissociation between global markers of bone formation and direct measurement of spinal bone formation in osteoporosis.

UNLABELLED: Regional bone metabolism measured using 18F-fluoride PET was assessed in 72 postmenopausal women classified as normal, osteopenic, or osteoporotic. Lower values of regional bone formation activity at the lumbar spine were seen in osteoporotic women, whereas global markers of bone formation were significantly increased. INTRODUCTION: Evaluations of global bone remodeling have revealed that increased bone turnover is a feature of patients with osteoporosis. The noninvasive functional imaging technique of 18F-fluoride positron emission tomography (PET) allows the direct quantitative assessment of bone metabolism at specific sites in the skeleton, including the clinically important site of the lumbar spine. MATERIALS AND METHODS: The aim of this study was to compare regional skeletal kinetics in 72 postmenopausal women (mean age, 61 years) classified as normal, osteopenic, or osteoporotic according to their BMD T score at the lumbar spine. Each woman had a dynamic PET scan of the lumbar spine after injection of 90 MBq 18F-fluoride ion and measurements of biochemical markers of bone formation and resorption. The arterial plasma input function was derived using aorta arterial activity from the PET image. Time-activity curves were obtained by placing regions of interest over the lumbar vertebrae. A three-compartmental model was used to calculate bone blood flow (K1) and the net plasma clearance of tracer to bone mineral (Ki), reflecting regional osteoblastic activity (ml/minutes/ml). Rate constants k2, k3, and k4, which describe transport between plasma, the extracellular fluid (ECF) compartment, and the bone mineral compartment, were also measured. RESULTS: The net uptake of fluoride to the bone mineral compartment (Ki) was significantly lower in the osteoporotic group compared with both the osteopenic and normal groups, with a mean difference of 0.005 ml/minutes/ml (16.7%). The fraction of the tracer in the extravascular tissue space that underwent specific binding to bone mineral (k3/k2 + k3) was also significantly reduced in the women classified as osteoporotic. In contrast, levels of bone-specific alkaline phosphatase (BSALP) were significantly higher in the osteoporotic group compared with the normal and osteopenic groups by 35% and 27%, respectively. A significant negative correlation (r = -0.41) was observed between levels of BSALP and the fraction of the tracer that underwent specific binding to bone mineral. CONCLUSION: Lower values of Ki, a measurement of regional bone formation activity, were seen in women classified as osteoporotic, whereas levels of BSALP, a measure of global bone formation, were significantly increased. These findings are suggestive of increased global skeletal bone turnover in women with postmenopausal osteoporosis but with relatively reduced regional bone formation at the predominantly trabecular site of the lumbar spine.

Absorptiometry, Photon↗

Addition of 18F-FDG-PET scans to radiotherapy planning of thoracic lymphoma.

BACKGROUND AND PURPOSE: FDG-PET possesses greater sensitivity and accuracy than computed tomography (CT) in detecting diseased lymph nodes. Though the FDG-PET scans are acquired for similar diagnostic reasons as CT, they are not used in the radiotherapy (RT) planning process. Successful tumourcidal dose is usually delivered but large volumes of normal and non-malignant tissues are irradiated due to the nature of lymphoma and also to the subjectivity of the field determining process. This study tries to lessen the subjectivity of the field determining process by the addition of currently acquired PET to the conventional thoracic lymphoma RT. The differences between retrospectively delineated volumes from CT and FDG-PET were compared and the effect of this additional information was evaluated. MATERIALS AND METHODS: Seventeen FDG-PET scans were registered to corresponding CT scans using rigid-body registration with negligible intra-observer variability. Comparisons were made between the volumes, lateral extensions and the most inferior point of the delineated gross tumour volumes (GTVs). RESULTS: For 1/17 patient data, no diseased volumes were delineated and in 6/17, no volumes were delineated on PET and yet in CT, masses up to 367.2 cm3 were outlined. From the 10 positive-CT and PET data, the GTV(PET) were smaller than GTV(CT) in six cases. Greater than 3.0 cm lateral disease extension differences were observed in 4/10 cases. Inferior tumour extents were confirmed in 6/10 cases whereas in 2/10 patients GTV(CT) was greater than 12.0 cm inferior compared to GTV(PET). CONCLUSIONS: FDG-PET data can be introduced to current thoracic lymphoma RT planning protocol with minimal intervention and changes. The subjectivity in the RT planning of thoracic lymphoma would be decreased with the addition of currently acquired FDG-PET data.

Adolescent↗

Diagnostic 131I whole body scanning after thyroidectomy and ablation for differentiated thyroid cancer.

OBJECTIVE: To assess the value of the diagnostic whole body (131)I scan after thyroidectomy and (131)I ablation. DESIGN: Retrospective analysis of all patients with differentiated thyroid cancer treated in one centre between 1990 and 2000. RESULTS: A total of 153 consecutive patients who underwent diagnostic scanning following ablative therapy were identified. This diagnostic scan was positive in 20 patients (13%) and faintly positive in 16 patients (11%). The majority (117 patients) had negative scans. Of the 20 patients with positive scans, four received no further treatment, nine showed no abnormal uptake following a second ablative (131)I dose and seven had uptake in the thyroid bed (six) or in neck nodes (one) after repeat ablation. OUTCOME: In the group with positive scans, the four patients who received no further treatment and the nine with a negative second ablation scan remained disease free during follow-up. No patient with a positive diagnostic scan received additional (131)I therapy which would not otherwise have been given based on the clinical findings, serum thyroglobulin (Tg) values or the presence of anti-Tg antibodies. Ten of the patients with negative scans developed recurrent disease which was always detected clinically or by a rising serum Tg value. CONCLUSIONS: Diagnostic whole body (131)I scans add little extra information and in our experience do not influence patient management. They should be reserved for patients in whom serum Tg levels are unreliable because of the presence of antibodies or when there is clinical suspicion of tumour.

Aged↗

Patient perceptions of professionalism in dentistry.

The purpose of this study was to examine how patients perceived the professionalism of University of Minnesota School of Dentistry students, faculty, and staff. Professionalism is defined by the authors as an image that will promote a successful relationship with the patient. Patients within comprehensive care clinics were asked to assess physical attributes and behaviors of the dental care providers using a questionnaire. The patients read statements dealing with characteristics of the dental care providers and responded as to whether they agreed, were neutral, or disagreed with the statement. The surveyed population consisted of 103 males and 97 females, 64 percent of whom lacked insurance coverage. Fifty-one percent of the patients were between the ages of forty-four and sixty-nine, but the overall age distribution was dispersed over a range of eighteen to one hundred. Our research found that all dental care providers displayed a professional appearance as well as behavior. The attire of the dental care provider affected the comfort and anxiety levels of patients, as did first impressions of both students and faculty. Most patients reported that students and faculty displayed effective time management and used appropriate language during the appointment. Finally, hairstyle, makeup, and jewelry appeared to have little effect on patients' opinions of the various dental care providers.

Adolescent↗

Acyclic analogues of adenosine bisphosphates as P2Y receptor antagonists: phosphate substitution leads to multiple pathways of inhibition of platelet aggregation.

Activation by ADP of both P2Y(1) and P2Y(12) receptors in platelets contributes to platelet aggregation, and antagonists at these receptor subtypes have antithrombotic properties. In an earlier publication, we have characterized the SAR as P2Y(1) receptor antagonists of acyclic analogues of adenine nucleotides, containing two phosphate groups on a symmetrically branched aliphatic chain, attached at the 9-position of adenine. In this study, we have focused on antiaggregatory effects of P2Y antagonists related to a 2-chloro-N(6)-methyladenine-9-(2-methylpropyl) scaffold, containing uncharged substitutions of the phosphate groups. For the known nucleotide (cyclic and acyclic) bisphosphate antagonists of P2Y(1) receptors, there was a significant correlation between inhibition of aggregation induced by 3.3 microM ADP in rat platelets and inhibition of P2Y(1) receptor-induced phospholipase C (PLC) activity previously determined in turkey erythrocytes. Substitution of the phosphate groups with nonhydrolyzable phosphonate groups preserved platelet antiaggregatory activity. Substitution of one of the phosphate groups with O-acyl greatly reduced the inhibitory potency, which tended to increase upon replacement of both phosphate moieties of the acyclic derivatives with uncharged (e.g., ester) groups. In the series of nonsymmetrically substituted monophosphates, the optimal antagonist potency occurred with the phenylcarbamate group. Among symmetrical diester derivatives, the optimal antagonist potency occurred with the di(phenylacetyl) group. A dipivaloyl derivative, a representative uncharged diester, inhibited ADP-induced aggregation in both rat (K(I) 3.6 microM) and human platelets. It antagonized the ADP-induced inhibition of the cyclic AMP pathway in rat platelets (IC(50) 7 microM) but did not affect hP2Y(1) receptor-induced PLC activity measured in transfected astrocytoma cells. We propose that the uncharged derivatives are acting as antagonists of a parallel pro-aggregatory receptor present on platelets, that is, the P2Y(12) receptor. Thus, different substitution of the same nucleoside scaffold can target either of two P2Y receptors in platelets.

Adenosine Diphosphate↗