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Biomedical subjects

A Cheng

Publications and source records attributed to A Cheng.

At least 37 records · Page 2Linked to original sources

Prospective clinical evaluation of an electronic portal imaging device.

PURPOSE: To determine whether the clinical implementation of an electronic portal imaging device can improve the precision of daily external beam radiotherapy. METHODS AND MATERIALS: In 1991, an electronic portal imaging device was installed on a dual energy linear accelerator in our clinic. After training the radiotherapy technologists in the acquisition and evaluation of portal images, we performed a randomized study to determine whether online observation, interruption, and intervention would result in more precise daily setup. The patients were randomized to one of two groups: those whose treatments were actively monitored by the radiotherapy technologists and those that were imaged but not monitored. The treating technologists were instructed to correct the following treatment errors: (a) field placement error (FPE) > 1 cm; (b) incorrect block; (c) incorrect collimator setting; (d) absent customized block. Time of treatment delivery was recorded by our patient tracking and billing computers and compared to a matched set of patients not participating in the study. After the patients radiation therapy course was completed, an offline analysis of the patient setup error was planned. RESULTS: Thirty-two patients were treated to 34 anatomical sites in this study. In 893 treatment sessions, 1,873 fields were treated (1,089 fields monitored and 794 fields unmonitored). Ninety percent of the treated fields had at least one image stored for offline analysis. Eighty-seven percent of these images were analyzed offline. Of the 1,011 fields imaged in the monitored arm, only 14 (1.4%) had an intervention recorded by the technologist. Despite infrequent online intervention, offline analysis demonstrated that the incidence of FPE > 10 mm in the monitored and unmonitored groups was 56 out of 881 (6.1%) and 95 out of 595 (11.2%), respectively; p < 0.01. A significant reduction in the incidence of FPE > 10 mm was confined to the pelvic fields. The time to treat patients in this study was 10.78 min (monitored) and 10.10 min (unmonitored). Features that were identified that prevented the technologists from recognizing more errors online include poor image quality inherent to the portal imaging device used in this study, artifacts on the portal images related to table supports, and small field size lacking sufficient anatomical detail to detect FPEs. Furthermore, tools to objectively evaluate a portal image for the presence of field placement error were lacking. These include magnification factor corrections between the simulation of portal image, online measurement tools, image enhancement tools, and image registration algorithms. CONCLUSION: The use of an electronic portal imaging device in our clinic has been implemented without a significant increase in patient treatment time. Online intervention and correction of patient positioning occurred rarely, despite FPEs of > 10 mm being present in more than 10% of the treated fields. A significant reduction in FPEs exceeding 10 mm was made in the group of patients receiving pelvic radiotherapy. It is likely that this improvement was made secondarily to a decrease in systematic error and not because of online interventions. More significant improvements in portal image quality and the availability of online image registration tools are required before substantial improvements can be made in patient positioning with online portal imaging.

Brain Neoplasms

Free radical mediated x-ray damage of model membranes.

The damaging effects of synchrotron-derived x rays on aqueous phospholipid dispersions have been evaluated. The effect of degree of lipid hydration, phospholipid chemical structure, mesophase identity, aqueous medium composition, and incident flux on the severity and progress of damage was quantified using time-resolved x-ray diffraction and chromatographic analysis of damage products. Electron spin resonance measurements of spin-trapped intermediates generated during irradiation suggest a free radical-mediated process. Surprisingly, radiation damage effects revealed by x-ray diffraction were imperceptible when the lamellar phases were prepared under water-stressed conditions, despite the fact that x-ray-induced chemical breakdown of the lipid occurred regardless of hydration level. Of the fully hydrated lipid systems studied, saturated diacyl-phosphatidylcholines were most sensitive to radiation damage compared to the ester- and ether-linked phosphatidylethanolamines and the ether-linked phosphatidylcholines. The inclusion of buffers or inorganic salts in the dispersing medium had only a minor effect in reducing damage development. A small inverse dose-rate effect was found when the x-ray beam intensity was changed 15-fold. These results contribute to our understanding of the mechanism of radiation damage, to our appreciation of the importance of monitoring both structure and composition when evaluating biomaterials radiation sensitivity, and to the development of strategies for eliminating or reducing the severity of damage due to an increasingly important source of x rays, synchrotron radiation. Because damage is shown to be free radical mediated, these results have an important bearing on age-related accumulation of free radicals in cells and how these might compromise membrane integrity, culminating in cell death.

1,2-Dipalmitoylphosphatidylcholine

The risks of hip fracture in older people from private homes and institutions.

This study aimed to determine whether the incidence of hip fracture is greater among those living in institutions compared with those living in private homes. Over two and a half years of surveillance, 1832 hip fractures were identified, of which 58% were sustained by those living in private homes and 42% by those living in institutions. The risks of hip fracture, unadjusted for age and sex, were 10.5 times greater for those living in institutions compared with those living in private homes. After adjusting for age and sex, these greatly increased risks were maintained, although for both men and women the risks decreased with age, such that at ages over 90 years the risks were not significantly different. Given these findings, hip fracture prevention strategies that focus particularly on individuals within institutions are highly commended.

Aged

Systematic verification of a three-dimensional electron beam dose calculation algorithm.

A three-dimensional electron beam dose calculation algorithm implemented on a commercial radiotherapy treatment planning system is described. The calculation is based on the M. D. Anderson Hospital (M.D.A.H.) pencil beam model, which uses the Fermi-Eyges theory of thick-target multiple Coulomb scattering. To establish the calculation algorithm's accuracy as well as its limitations, it was systematically and extensively tested and evaluated against a set of benchmark measurements. Various levels of dose and spatial tolerances were used to validate the calculation quantitatively. Results are presented in terms of the percentage of data points meeting a specific tolerance level. The algorithm's ability to accurately simulate commonly used clinical setup geometries, including standard or extended SSDs, blocked fields, irregular surfaces, and heterogeneities, is demonstrated. Regions of disagreement between calculations and measurements are also shown. The clinical implication of such disagreements is addressed, and the algorithmic assumptions involved are discussed.

Algorithms

Telecardiology: supporting the decision-making process in general practice.

To assess the initial phase of a telecardiology diagnostic service for general practitioners (GPs), we provided 93 GPs in 26 health centres with direct telephone access to a cardiologist, and equipped them with hand-held, automatic standard 12-lead electrocardiogram (ECG) transmitters for on-line cardiac consultations and ECG interpretation in their daily practice. Clinical details, reason for consultation and the ECG signal were transmitted from the GPs' practices or the patients' homes. A consultation followed and a full report, including ECG print-out, was then sent to the GP. During an 18-month study period, 2563 consultations were carried out. The system allowed the identification of 479 patients (19%) with urgent cardiac problems and the remaining 2084 (81%) in whom admission or outpatient investigation was unnecessary. Following the study, we distributed a questionnaire asking the GPs to rate the quality, define the use and consider the benefit of the service to their daily practice. We conclude that a telecardiology diagnosis and ECG interpretation service is simple, reliable and efficacious in routine primary care. It offers instant access to cardiac assessment and supports the decision-making process of GPs. A preliminary cost comparison with a conventional referral indicated that a teleconsultation was substantially cheaper. We expect that the future incorporation of teleechocardiography would expand the scope of telecardiology even further and allow comprehensive cardiology consultations.

Cardiology

Fletcher Challenge-University of Auckland Heart & Health Study: design and baseline findings.

AIMS: The aims of this prospective observational study are to determine the relationship of sociodemographic factors, psychological factors and several factors measured in blood, with the risk of coronary heart disease (CHD) in a New Zealand population. METHODS: Participants were recruited from two sources: employees of the Fletcher Challenge Group and individuals listed on the general electoral roll for the Auckland region. Baseline and follow up risk factor data were obtained from a questionnaire, blood samples and a simple physical examination. Outcome data on deaths and hospitalisations due to coronary heart disease will be obtained primarily through linkage of participant identifiers to data collected nationally by the New Zealand Health Information Service. RESULTS: A total of 10,529 individuals agreed to participate (8011 from Fletcher Challenge and 2518 from the electoral roll), representing a response rate of 74%. Within the study population, there was a broad distribution of sociodemographic characteristics including ethnicity-10% of participants were Maori and 5% were of Pacific Islands origin. There was also wide heterogeneity of coronary heart disease risk as judged from the distributions of established risk factors at baseline-5% of participants had evidence of existing coronary heart disease, a quarter were current smokers, a sixth were nondrinkers, almost a half were overweight, a fifth had blood pressure > or = 150/95 mmHg or were receiving antihypertensive treatment and a sixth had cholesterol levels > or = 6.5 mmol/L. CONCLUSIONS: This is the first, large scale prospective observational study of the determinants of coronary heart disease in a New Zealand population. The study participants represent a broad cross section of society, with wide variation in sociodemographic characteristics and coronary heart disease risk. Initial results concerning the relationships of primary interest should be available within 5 years when sufficient coronary heart disease events have been documented to allow reliable analyses.

Adult

Tissue- and species-specific expression of sp56, a mouse sperm fertilization protein.

Mouse sperm recognize and bind to ZP3, one of three glycoproteins in the egg's zona pellucida. A mouse sperm protein, sp56, was identified that has the characteristics expected of the sperm protein responsible for recognition of ZP3. The complementary DNA encoding sp56 was isolated, and its primary sequence indicates that sp56 is a member of a superfamily of protein receptors. It was shown that sp56 expression is restricted to mouse spermatids and that the presence or absence of sp56 on sperm from different species accounts for species specificity of sperm-egg recognition in mice.

Amino Acid Sequence

Alteration in nicotine binding sites in Parkinson's disease, Lewy body dementia and Alzheimer's disease: possible index of early neuropathology.

High-affinity nicotine binding, considered to primarily reflect the presence of CNS alpha 4 beta 2 nicotinic receptor subunits, was examined autoradiographically in brain regions most severely affected by Alzheimer and Parkinson types of pathology. In the midbrain, the high density of binding associated with the pars compacta of the substantia nigra was extensively reduced (65-75%, particularly in the lateral portion) in both Lewy body dementia and Parkinson's disease. Since loss of dopaminergic neurons in Lewy body dementia was only moderate (40%), loss or down-regulation of the nicotinic receptor may precede degeneration of dopaminergic neurons in this region. In the dorsolateral tegmentum, where diffuse cholinergic perikarya are located, nicotine binding was highly significantly decreased in both Lewy body dementia and Parkinson's disease with almost no overlap between the normal and disease groups, indicative of a major pathological involvement in or around the pedunculopontine cholinergic neurons. In the hippocampus, binding was decreased around the granular layer in Lewy body dementia and Alzheimer's disease, although unchanged in the stratum lacunosum moleculare, where binding was relatively higher. Dense bands of receptor binding in the presubiculum and parahippocampal gyrus--areas of highest binding in human cortex--were diminished in Alzheimer's disease but not Lewy body dementia. In temporal neocortex there were reductions in Alzheimer's disease throughout the cortical layers but in Lewy body dementia only in lower layers, in which Lewy bodies are concentrated. Abnormalities of the nicotinic receptor in the diseases examined appear to be closely associated with primary histopathological changes: dopaminergic cell loss in Parkinson's disease and Lewy body dementia, amyloid plaques and tangles in subicular and entorhinal areas in Alzheimer's disease. Loss or down-regulation of the receptor may precede neurodegeneration.

Acetylcholinesterase

Kinetics of lipid phase changes.

In the past two years, the kinetics of transitions involving the assorted lamellar and inverted hexagonal and cubic phases in bulk hydrated lipid systems have been established using a variety of physical techniques. In several cases, the kinetic data have lead to a transition mechanisms being deciphered.

Crystallization

Immuno-colloidal gold labeled surface replica, and its application to detect sp56, the egg recognition and binding protein, on the mouse spermatozoon.

Using immuno-colloidal gold surface replicas (IGSR), we developed a method to demonstrate surface antigens in a whole view of a cell at the EM level. In this study, a monoclonal antibody (MAB) 7C5 directed against sp56, which is a mouse sperm protein (M(r) = 56,000 daltons) and has specific affinity for the zona pellucida, was used as primary antibody. Fixed mouse spermatozoa were incubated with primary antibody and colloidal gold-labeled secondary antibody on a slide glass. Used gold particles were 10, 20 or 30 nm in diameter. The spermatozoa were then critical point dried, and replicated with platinum and carbon. Replicas were examined with a transmission EM. The result suggests that sp56 is located on the outer surface of the plasma membrane covering approximately 2/3 of dorsal edge of the sperm head, but it is virtually absent in the tapered apical tip. When 10 and 20 nm colloidal particles were used, about 500 particles were observed on one side of the flat sperm head. Although the large 30 nm particles were easily recognized in low magnification figures, the attached number on the sperm head was generally lower than the number of 10 or 20 nm particles observed. By this method, we could effectively demonstrate the localization of a surface antigen in a wide cell view with clear landmarks.

Animals

Scrub typhus pneumonitis with delayed resolution.

A 35-year-old lady was admitted to hospital with fever and dry cough. Chest radiograph showed bilateral basal infiltrate. Her Weil-Felix test was strongly positive (OX-K > 1:160) and her fever came down with intravenous tetracycline. There was no improvement in the lung shadow and spirometry showed a severe restrictive defect. Open lung biopsy confirmed the diagnosis of interstitial pneumonitis. CT of thorax 6 months after presentation showed partial resolution of the interstitial shadow.

Adult

Is weekly port filming adequate for verifying patient position in modern radiation therapy?

PURPOSE: The objective of this study is to use daily electronic portal imaging to evaluate weekly port filming in detecting patient set-up position. METHODS AND MATERIALS: A computer-based portal alignment method was used to quantify the field displacements on 191 digitized weekly port films and 848 daily electronic portal images in 21 radiation therapy patients. An electronic portal image data set as a control for actual daily treatment position was used to evaluate weekly port films with respect to same-day field displacement, rate of field placement error detection, and prediction of subsequent daily field displacements. RESULTS: The field displacements measured on a port film frequently deviated from the corresponding field displacements on the electronic portal image obtained in the same treatment set-up. A linear regression analysis showed that the curves fitted to the same-day field displacements had slopes that differed significantly from unity (p < 0.001). Overall, the respective frequencies of field placement error, beyond clinical tolerance limits of 5, 7, and 10 mm (corresponding to head and neck, thoracic, and pelvic sites) for port filming and electronic portal imaging were 11% and 14% (p = 0.4) in the X-direction (lateral or anteroposterior) and 24% and 13% (p = .0001) in the Y-direction (caphalad-caudad). When the data were broken down by anatomical region, this discrepancy was found to be mainly due to the differences in the thorax, and head and neck image data sets. For thoracic fields, error in Y-shifts was 28% by port filming, but only 9% by portal imaging (p = 0.01). In the head and neck region, 18% of the port films exceeded tolerance, whereas only 6% of the electronic portal images did (p = 0.0001). Field displacements on the treatment set-ups between the acquisition of port films were not predicted by those films. CONCLUSION: There are discrepancies between the field displacements and field placement errors detected by weekly port films and daily electronic portal images. This study suggests that improved methods of treatment verification may be necessary in modern radiation therapy.

Diagnostic Imaging

Kinetics and mechanism of the barotropic lamellar gel/lamellar liquid crystal phase transition in fully hydrated dihexadecylphosphatidylethanolamine: a time-resolved x-ray diffraction study using pressure jump.

The kinetics and mechanism of the barotropic lamellar gel (L beta')/lamellar liquid crystal (L alpha) phase transition in fully hydrated 1,2-dihexadecyl-sn-glycero-3-phosphoethanolamine (DHPE) has been studied using time-resolved x-ray diffraction (TRXRD). The phase transition was induced by pressure jumps of varying amplitudes in both the pressurization and depressurization directions at controlled temperature (78 degrees C). Both low- and wide-angle diffracted x rays were recorded simultaneously in live time using an x-ray-sensitive image intensifier coupled to a CCD camera and Super-VHS videotape recorder. Such an arrangement allowed for the direct and quantitative characterization of the long- (lamellar repeat spacing) and short-range order (chain packing) during a kinetic experiment. The image-processed live-time x-ray diffraction data were fitted using a nonlinear least-squares model, and the parameters of the fits were monitored continuously throughout the transition. The pressure-induced transitions from the L alpha to the L beta' phase and from the L beta' to the L alpha phase was two-state (no formation of intermediates apparent during the transition) to within the sensitivity limits of the method. The corresponding transit time (the time during which both phases coexist) associated with the long- and short-range order of the pressurization-induced L alpha-to-L beta' phase transition decreased to a limiting value of approximately 50 ms with increasing pressure jump amplitude. This limiting value was close to the response time of the detector/recording system. Thus, the intrinsic transit time of this transition in fully hydrated DHPE at 78 degrees C was less than or equal to 50 ms. In contrast, the depressurization-induced L beta'-to-L alpha phase transition was slower, taking approximately 1 s to complete, and occurred with no obvious dependence of the transit time on pressure jump amplitude. In the depressurization jump experiment, the lipid responded rapidly to the pressure jump in the L beta' phase up to the rate-determining L beta'-to-L alpha transition. Such behavior was examined carefully, as it could complicate the interpretation of phase transition kinetic measurements.

Crystallization

Sperm-egg recognition in the mouse: characterization of sp56, a sperm protein having specific affinity for ZP3.

Recognition between mammalian gametes occurs when the plasma membrane of the sperm head binds to the zona pellucida (ZP), an extracellular coat surrounding eggs. ZP3, one of three glycoproteins in the ZP, is the egg protein recognized by sperm. A mouse sperm surface protein, sp56 (M(r) = 56,000), has been identified on the basis of its specific affinity for ZP3 (Bleil, J. D., and P. M. Wassarman. 1990. Proc. Natl. Acad. Sci. USA. 87:5563-5567). Studies presented here were designed to characterize mouse sperm sp56 and to further test whether or not this protein specifically recognizes ZP3. sp56 was purified by both ZP3 affinity chromatography and by ion exchange chromatography followed by size-exclusion chromatography. The purified native protein eluted from size-exclusion columns as a homomultimer (M(r) approximately 110,000). Each monomer of the protein contains intramolecular disulfide bonds, consistent with its extracellular location. Immunohistochemical and immunoblotting studies, using monoclonal antibodies, demonstrated that sp56 is a peripheral membrane protein located on the outer surface of the sperm head plasma membrane, precisely where sperm bind ZP3. Results of crosslinking experiments demonstrated that the ZP3 oligosaccharide recognized by sperm has specific affinity for sp56. Collectively, these results suggest that sp56 may be the sperm protein responsible for sperm-egg recognition in the mouse.

Amino Acid Sequence

The incidence of ophthalmopathy after radioiodine therapy for Graves' disease: prognostic factors and the role of methimazole.

Radioactive iodine-131 (RAI) has been reported to be associated with a high incidence of development or exacerbation of Graves' ophthalmopathy (GO). This is thought to be associated with a surge of autoantibodies after RAI therapy. The role of methimazole (MMI), which possesses immunomodulatory action, in the prevention of GO was explored by studying 114 patients with Graves' disease. They were assigned randomly to receive either RAI alone or adjunctive antithyroid drugs, which consisted of MMI and L-T4 as a block-replacement therapy for 12 months and were followed for 2 yr. Thirty-five patients (30.7%) had GO at presentation. Twenty-one (18%) patients developed new GO, and six had worsening of preexisting GO. The development of hypothyroidism (P < 0.01) and an elevation of TSH (P < 0.05) were associated with increased risk of development or exacerbation of GO. The chance of development or exacerbation of GO is higher in those with no ophthalmopathy than in those with preexisting GO at presentation (P = 0.002). The incidence of development or exacerbation of GO was similar in the two treatment groups (RAI, 22.8%; adjunctive antithyroid drugs, 23.7%; P = NS). MMI was able to suppress the surge of TSH receptor antibody (TRAB) after RAI, but a surge in TRAB was not of prognostic significance for the development of GO after RAI. Patients who developed or had exacerbation of GO actually had lower TRAB at presentation (P = 0.02). We conclude that hypothyroidism with elevated TSH is an important adverse factor for the development or exacerbation of GO, and MMI was unable to prevent the development or exacerbation of GO after RAI.

Adult

An evaluation of two methods of anatomical alignment of radiotherapy portal images.

PURPOSE: Two techniques have been developed at our institution to allow anatomical registration of digitized portal images to a simulation film. Accuracy of the portal image alignment methods is tested and single intrauser and multiple interuser variation is examined using each technique. METHODS AND MATERIALS: Method one requires the identification of anatomical fiducial points on a simulation image and its corresponding portal image. The parameters required to align the corresponding points are calculated by a least squares fit algorithm. Method two uses an anatomical template generated from the simulation image and superimposing it upon a portal image. The template is then adjusted by a computer mouse to obtain the best subjective anatomical fit on the portal image. Megavoltage portal images of a skull phantom with various known shifts and eight clinical image files were aligned by each method. Each data set was aligned several times by both a single user and multiple users. RESULTS: Alignment of the anatomical phantom portal images demonstrates an accuracy of less than 0.8 +/- 0.9 mm and 0.7 +/- 1.0 degrees with either method. As out of plane rotation increased from 0 to 5 degrees, simulating out of plane malpositioning, alignment orthogonal to the plane of rotation worsened to 1.5 +/- 1.1 mm with the point method and 2.4 +/- 1.6 mm with the template method. Alignment parallel to the axis of the gantry rotation was insensitive to this change and remained constant as did the rotational alignment parameters. For the clinical image files the magnitude of variation for a single user is typically less than +/- 1 mm or +/- 1 degree. The magnitude of variation of alignment increased when multiple users aligned the same image files. The variation was dependent upon anatomical site and to a lesser degree the method of alignment used. The root mean square deviation of translational shifts range from +/- 0.68 mm when using the template method in the pelvis to as high as +/- 2.94 mm with the template method to align abdominal portal images. In the thorax and pelvis translational alignments along the horizontal axis were more precise than along the vertical axis. Multiple user variability was in part due to poor image quality, user experience, non rigidity of the anatomical features, and the difficulty in locating an exact point on a continuous anatomical structure. CONCLUSION: In well controlled phantom studies both the fiducial point and template method provide similar and adequate results. The phantom studies show that alignment error and variance increase with distortion in anatomical features secondary to out of plane rotations. In clinical situations intrauser variation is small, however, multiple interuser variation is larger. The magnitude of variation is dependent upon the anatomical site aligned.

Computer Simulation