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Biomedical subjects

E Ford

Publications and source records attributed to E Ford.

At least 19 recordsLinked to original sources

Development of an integrated diabetes prevention program with First Nations in Canada.

Type 2 diabetes mellitus is a major cause of morbidity and mortality among First Nations in Canada. We used multiple research methods to develop an integrated multi-institutional diabetes prevention program based on the successful Sandy Lake Health and Diabetes Project and Apache Healthy Stores programs. In-depth interviews, a structured survey, demonstration and feedback sessions, group activities, and meetings with key stakeholders were used to generate knowledge about the needs and resources for each community, and to obtain feedback on SLHDP interventions. First Nations communities were eager to address the increasing epidemic of diabetes. Educating children through a school prevention program was the most popular proposed intervention. Remote communities had poorer access to healthy foods and more on-reserve media and services than the smaller semi-remote reserves. While the reserves shared similar risk factors for diabetes, variations in health beliefs and attitudes and environmental conditions required tailoring of programs to each reserve. In addition, it was necessary to balance community input with proven health promotion strategies. This study demonstrates the importance of formative research in developing integrated health promotion programs for multiple communities based on previously evaluated studies.

Community Health Services↗

Developments in megavoltage cone beam CT with an amorphous silicon EPID: reduction of exposure and synchronization with respiratory gating.

We have studied the feasibility of a low-dose megavoltage cone beam computed tomography (MV CBCT) system for visualizing the gross tumor volume in respiratory gated radiation treatments of nonsmall-cell lung cancer. The system consists of a commercially available linear accelerator (LINAC), an amorphous silicon electronic portal imaging device, and a respiratory gating system. The gantry movement and beam delivery are controlled using dynamic beam delivery toolbox, a commercial software package for executing scripts to control the LINAC. A specially designed interface box synchronizes the LINAC, image acquisition electronics, and the respiratory gating system. Images are preprocessed to remove artifacts due to detector sag and LINAC output fluctuations. We report on the output, flatness, and symmetry of the images acquired using different imaging parameters. We also examine the quality of three-dimensional (3D) tomographic reconstruction with projection images of anthropomorphic thorax, contrast detail, and motion phantoms. The results show that, with the proper choice of imaging parameters, the flatness and symmetry are reasonably good with as low as three beam pulses per projection image. Resolution of 5% electron density differences is possible in a contrast detail phantom using 100 projections and 30 MU. Synchronization of image acquisition with simulated respiration also eliminated motion artifacts in a moving phantom, demonstrating the system's capability for imaging patients undergoing gated radiation therapy. The acquisition time is limited by the patient's respiration (only one image per breathing cycle) and is under 10 min for a scan of 100 projections. In conclusion, we have developed a MV CBCT system using commercially available components to produce 3D reconstructions, with sufficient contrast resolution for localizing a simulated lung tumor, using a dose comparable to portal imaging.

Artifacts↗

Effect of respiratory gating on reducing lung motion artifacts in PET imaging of lung cancer.

Positron emission tomography (PET) has shown an increase in both sensitivity and specificity over computed tomography (CT) in lung cancer. However, motion artifacts in the 18F fluorodioxydoglucose (FDG) PET images caused by respiration persists to be an important factor in degrading PET image quality and quantification. Motion artifacts lead to two major effects: First, it affects the accuracy of quantitation, producing a reduction of the measured standard uptake value (SUV). Second, the apparent lesion volume is overestimated. Both impact upon the usage of PET images for radiation treatment planning. The first affects the visibility, or contrast, of the lesion. The second results in an increase in the planning target volume, and consequently a greater radiation dose to the normal tissues. One way to compensate for this effect is by applying a multiple-frame capture technique. The PET data are then acquired in synchronization with the respiratory motion. Reduction in smearing due to gating was investigated in both phantoms and patient studies. Phantom studies showed a dependence of the reduction in smearing on the lesion size, the motion amplitude, and the number of bins used for data acquisition. These studies also showed an improvement in the target-to-background ratio, and a more accurate measurement of the SUV. When applied to one patient, respiratory gating showed a 28% reduction in the total lesion volume, and a 56.5% increase in the SUV. This study was conducted as a proof of principle that a gating technique can effectively reduce motion artifacts in PET image acquisition.

Algorithms↗

Fluoroscopic evaluation of diaphragmatic motion reduction with a respiratory gated radiotherapy system.

We report on initial patient studies to evaluate the performance of a commercial respiratory gating radiotherapy system. The system uses a breathing monitor, consisting of a video camera and passive infrared reflective markers placed on the patient's thorax, to synchronize radiation from a linear accelerator with the patient's breathing cycle. Six patients receiving treatment for lung cancer participated in a study of system characteristics during treatment simulation with fluoroscopy. Breathing synchronized fluoroscopy was performed initially without instruction, followed by fluoroscopy with recorded verbal instruction (i.e., when to inhale and exhale) with the tempo matched to the patient's normal breathing period. Patients tended to inhale more consistently when given instruction, as assessed by an external marker movement. This resulted in smaller variation in expiration and inspiration marker positions relative to total excursion, thereby permitting more precise gating tolerances at those parts of the breathing cycle. Breathing instruction also reduced the fraction of session times having irregular breathing as measured by the system software, thereby potentially increasing the accelerator duty factor and decreasing treatment times. Fluoroscopy studies showed external monitor movement to correlate well with that of the diaphragm in four patients, whereas time delays of up to 0.7 s in diaphragm movement were observed in two patients with impaired lung function. From fluoroscopic observations, average patient diaphragm excursion was reduced from 1.4 cm (range 0.7-2.1 cm) without gating and without breathing instruction, to 0.3 cm (range 0.2-0.5 cm) with instruction and with gating tolerances set for treatment at expiration for 25% of the breathing cycle. Patients expressed no difficulty with following instruction for the duration of a session. We conclude that the external monitor accurately predicts internal respiratory motion in most cases; however, it may be important to check with fluoroscopy for possible time delays in patients with impaired lung function. Furthermore, we observe that verbal instruction can improve breathing regularity, thus improving the performance of gated treatments with this system.

Diaphragm↗

Racial and ethnic differences in the use of cardiovascular procedures: findings from the California Cooperative Cardiovascular Project.

OBJECTIVES: This study used data from the California Cooperative Cardiovascular Project to examine the use of invasive and noninvasive cardiovascular procedures among Whites, African Americans, and Hispanics. METHODS: The use of catheterization, percutaneous transluminal coronary angioplasty (PTCA), coronary artery bypass graft (CABG) surgery, and several noninvasive tests among all patients 65 years or older with a confirmed acute myocardial infarction in nonfederal hospitals from 1994 to 1995 was studied. RESULTS: African Americans (n = 527) were less likely than Whites (n = 9489) to have received catheterization (adjusted odds ratio [OR] = 0.62, 95% confidence interval [CI] = 0.50, 0.76), PTCA (OR = 0.64, 95% CI = 0.49, 0.85), or CABG surgery (OR = 0.42, 95% CI = 0.27, 0.64); somewhat more likely to have received a stress test or an echocardiogram; and equally likely to have received a multiple-gated acquisition scan. Hispanics (n = 689) also were less likely than Whites to have received catheterization (OR = 0.82, 95% CI = 0.68, 0.98) or PTCA (OR = 0.58, 95% CI = 0.45, 0.75). CONCLUSIONS: African Americans were less likely than Whites to undergo costly invasive cardiovascular procedures. In addition, Hispanics were less likely than Whites to have received catheterization and PTCA.

APACHE↗

Seimatoantlerium tepuiense gen. nov., a unique epiphytic fungus producing taxol from the Venezuelan Guyana.

Seimatoantlerium gen. nov., type species, S. tepuiense sp. nov. is proposed for an acervular fungus producing 4-septate, holoblastic conidia with 6-8 unbranched, apical appendages that dehisce as an appendage apparatus and also commonly possessing one or two exogenous basal appendages as well as a pedicel. It is compared with Seimatosporium, Seimatosporiopsis, and other genera. It is epiphytic on Maguireothamnus speciosus, a rubiaceous plant endemic to the tepuis of southeastern Venezuela. It produces the anti-oomycetous anticancer compound, taxol, as shown by immunological and spectroscopic methods. Taxol production is discussed relative to the ability of this fungus to exist in an extremely moist ecosystem, as well as to its relationship to other plant associated fungi.

Antineoplastic Agents, Phytogenic↗

The Oct-1 POU domain activates snRNA gene transcription by contacting a region in the SNAPc largest subunit that bears sequence similarities to the Oct-1 coactivator OBF-1.

The RNA polymerases II and III snRNA gene promoters contain an octamer sequence as part of the enhancer and a proximal sequence element (PSE) as part of the core promoter. The octamer and the PSE bind the POU domain activator Oct-1 and the basal transcription factor SNAPc, respectively. Oct-1, but not Oct-1 with a single E7R mutation within the POU domain, binds cooperatively with SNAPc and, in effect, recruits SNAPc to the PSE. Here, we show that SNAPc recruitment is mediated by an interaction between the Oct-1 POU domain and a small region of the largest subunit of SNAPc, SNAP190. This SNAP190 region is strikingly similar to a region in the B-cell-specific Oct-1 coactivator, OBF-1, that is required for interaction with octamer-bound Oct-1 POU domain. The Oct-1 POU domain-SNAP190 interaction is a direct protein-protein contact as determined by the isolation of a switched specificity SNAP190 mutant that interacts with Oct-1 POU E7R but not with wild-type Oct-1 POU. We also show that this direct protein-protein contact results in activation of transcription. Thus, we have identified an activation target of a human activator, Oct-1, within its cognate basal transcription complex.

Amino Acid Sequence↗

Lung cancer deaths in the United States from 1979 to 1992: an analysis using multiple-cause mortality data.

BACKGROUND: We sought to describe trends in the presence of lung cancer at the time of death in the United States from 1979 to 1992. METHODS: We analysed death certificate reports in the Multiple-Cause Mortality Files compiled by the National Center for Health Statistics, searching for any mention of lung cancer, lung cancer as the underlying cause of death, and comorbid conditions. RESULTS: Of the 29,042,213 decedents in the study period, 1,892,129 (6.5%) had a diagnosis of lung cancer listed on their death certificates; of these 1,892,129 decedents, 1,734,767 (91.7%) had lung cancer listed as the underlying cause of death. Decedents with lung cancer listed as being present but not the underlying cause of death were more likely to be male (relative risk [RR] 1.16, 95% confidence interval [CI]: 1.15-1.17), and older (RR 4.61, 95% CI: 4.35-4.88 for decedents older than 85 compared to those aged less than 44), but less likely to be black than white (RR 0.88, 95% CI: 0.87-0.90). The mortality rate, age-adjusted to the 1980 population, increased 23.0%, from 47.9 per 100,000 in 1979 to 58.9 per 100,000 in 1992. Over the study period, black men had the highest mortality rates (117.3-125.2 per 100,000), followed by white men (81.7-88.7 per 100,000), men of other races (37.4-46.7 per 100,000), white women (22.1-39.1 per 100,000), black women (21.4-38.2 per 100,000), and women of other races (12.6-18.1 per 100,000). Age-adjusted, state specific rates varied threefold, from 30.4 per 100,000 in Utah to 93.9 per 100,000 in Nevada. CONCLUSIONS: We conclude that the underlying cause of death data base, which captures almost 92% of decedents with lung cancer present, accurately tracks lung cancer mortality trends in the US. Mortality rates of lung cancer, which are decreasing among men, continue to increase among women.

Adolescent↗

Characterization of a trimeric complex containing Oct-1, SNAPc, and DNA.

The human small nuclear (sn) RNA promoters contain a proximal sequence element (PSE), which recruits the basal transcription factor SNAPc, and a distal sequence element characterized by an octamer sequence, which recruits the POU domain transcription factor Oct-1. The Oct-1 POU domain and SNAPc bind cooperatively to probes containing a PSE and an octamer sequence, and this effect contributes to efficient transcription in vitro. In vivo, however, Oct-1 regions outside of the POU domain can activate snRNA gene transcription. Here, we have examined whether the role of these regions is to contribute to cooperative binding with SNAPc. We find that they indeed improve cooperative binding, but most of the effect is nevertheless mediated by just the POU domain. This suggests that Oct-1 activates transcription of snRNA genes in at least two steps, recruitment of SNAPc mediated primarily by the POU domain, and a later step mediated by regions outside of the POU domain. We also show that a PSE-binding complex observed in nuclear extracts consists of Oct-1 and SNAPc. Although Oct-1 cannot bind effectively to the PSE probe on its own, in the complex it contacts DNA. Thus, in a nuclear extract, SNAPc can recruit Oct-1 to a probe to which Oct-1 cannot bind on its own.

Base Sequence↗

Development of tolerance in mice to the sedative effects of the neuroactive steroid minaxolone following chronic exposure.

Minaxolone is a potent ligand for the neurosteroid binding site of the GABAA, receptor. In radioligand binding studies to rat brain membranes, minaxolone caused a 69% increase in [3H]muscimol binding and a 25% increase in [3H]flunitrazepam binding and inhibited the binding of [3H]TBOB with an IC50 of 1 microM. In mice, minaxolone (100 mg/kg, orally) had marked sedative effects as indicated by a reduction in locomotor activity. Chronic dosing with minaxolone (100 mg/kg, orally, once daily for 7 days) resulted in a loss of sedative response to an acute dose of the drug, indicating development of tolerance. Chronic dosing with temazepam (10 mg/kg, orally, once daily for 7 days) resulted in the development of tolerance to an acute dose of temazepam; however, the two drugs did not appear to be cross-tolerant, indicating that they may have a different mechanism of action at the level of the GABAA receptor.

Anesthetics↗

The role of the IsK protein in the specific pharmacological properties of the IKs channel complex.

IKs channels are composed of IsK and KvLQT1 subunits and underly the slowly activating, voltage-dependent IKs conductance in heart. Although it appears clear that the IsK protein affects both the biophysical properties and regulation of IKs channels, its role in channel pharmacology is unclear. In the present study we demonstrate that KvLQT1 homopolymeric K+ channels are inhibited by the IKs blockers 293B, azimilide and 17-beta-oestradiol. However, IKs channels induced by the coexpression of IsK and KvLQT1 subunits have a 6-100 fold higher affinity for these blockers. Moreover, the IKs activators mefenamic acid and DIDS had little effect on KvLQT1 homopolymeric channels, although they dramatically enhanced steady-state currents through heteropolymeric IKs channels by arresting them in an open state. In summary, the IsK protein modulates the effects of both blockers and activators of IKs channels. This finding is important for the action and specificity of these drugs as IsK protein expression in heart and other tissues is regulated during development and by hormones.

Animals↗

Visual attention and perception in patients with Huntington's disease: comparisons with other subcortical and cortical dementias.

Shifts in attention were examined in patients with Huntington's disease (HD) using a divided attention paradigm that involved the presentation of global-local stimuli. The HD patients' pattern of performance was compared to the previously reported results of groups of patients with Alzheimer's disease (AD; Filoteo et al., 1992) or Parkinson's disease (PD; Filoteo et al., 1994). Across consecutive trials of the divided attention task, a visual target could appear at either the same global-local level or at a different level. When the target changed levels across consecutive trials, the AD patients demonstrated an impairment in disengaging attention from the level at which the last target appeared, whereas the PD patients were impaired in maintaining their attention at the previously attended level. In contrast to these patterns of performances, the HD patients did not demonstrate a significant impairment in shifting attention between hierarchical levels. Both the AD and the PD patients' abnormal shifting ability was significantly related to the number of errors they made in identifying target stimuli; however, the pattern of the relationship was qualitatively distinct. These results suggest that different attentional mechanisms may underlie AD and PD patients' visual-perceptual deficits. The HD patients' shifting ability was not related to the number of errors they made in identifying target stimuli, suggesting that a different mechanism may account for the visual-perceptual impairments exhibited by these patients.

Aged↗

Education needs in palliative care.

A literature review confirms a need for improved medical education on death, dying, terminal illness, and bereavement, and so palliative care, from 1900 until the present time in the UK, Australia, New Zealand, USA, and Canada. The origins of the hospice movement and its influence are also discussed. Current palliative care teaching is recorded in a table of the courses initiated in medical schools which demonstrates a lack of formal courses. An appreciation of the issues surrounding these topics is required for the appropriate provision of palliative care, most importantly good communication and symptom control. These together with the issues of development of attitudes towards death, delivering bad news of serious illness, recognition of palliative care as a philosophy, psychosocial aspects of care and counselling the bereaved are included in the recommendations for co-ordinated interdepartmental teaching. This acquisition of knowledge, development of attitudes, and improvement of skills in palliative care can be achieved through the use of small group work and role-play exercises as well as formal lectures and experience at a hospice. Rectification of these curricula omissions will provide future doctors in a caring and competent manner with the ability to permit a dignified and 'good' death for the terminally ill.

Australia↗