Biomedical subjects

J Keegan

Publications and source records attributed to J Keegan.

At least 19 recordsLinked to original sources

PubMed2000

The E23 early gene of Drosophila encodes an ecdysone-inducible ATP-binding cassette transporter capable of repressing ecdysone-mediated gene activation.

At the onset of Drosophila metamorphosis, the steroid hormone 20-OH ecdysone directly induces a small number of early puffs in the polytene chromosomes of the larval salivary gland. Proteins encoded by the early genes corresponding to these transcriptional puffs then regulate the activity of both the early puffs themselves and a much larger set of late puffs. Three of these early genes encode transcription factors that play critical regulatory roles during metamorphosis. Here we report the cloning, DNA sequence, genomic structure, ecdysone inducibility, and temporal expression of an early gene residing in the 23E early puff and denoted E23 (Early gene at 23). In contrast to other early genes, E23 encodes a protein with similarity to ATP-binding cassette transporters. Using heat shock-inducible transgenes, we found that E23 overexpression not only produces phenotypic abnormalities and lethality, but also interferes with ecdysone-mediated gene activation, demonstrating that E23 is capable of modulating the ecdysone response. Our results suggest the existence of a previously unrecognized regulatory mechanism for modulating steroid hormone signaling in Drosophila.

ATP-Binding Cassette Transporters↗

PubMed2000

Coronary artery imaging in grown up congenital heart disease: complementary role of magnetic resonance and x-ray coronary angiography.

BACKGROUND: There is a high incidence of anomalous coronary arteries in subjects with congenital heart disease. These abnormalities can be responsible for myocardial ischemia and sudden death or be damaged during surgical intervention. It can be difficult to define the proximal course of anomalous coronary arteries with the use of conventional x-ray coronary angiography. Magnetic resonance coronary angiography (MRCA) has been shown to be useful in the assessment of the 3-dimensional relationship between the coronary arteries and the great vessels in subjects with normal cardiac morphology but has not been used in patients with congenital heart disease. METHODS AND RESULTS: Twenty-five adults with various congenital heart abnormalities were studied. X-ray coronary angiography and respiratory-gated MRCA were performed in all subjects. Coronary artery origin and proximal course were assessed for each imaging modality by separate, blinded investigators. Images were then compared, and a consensus diagnosis was reached. With the consensus readings for both magnetic resonance and x-ray coronary angiography, it was possible to identify the origin and course of the proximal coronary arteries in all 25 subjects: 16 with coronary anomalies and 9 with normal coronary arteries. Respiratory-gated MRCA had an accuracy of 92%, a sensitivity of 88%, and a specificity of 100% for the detection of abnormal coronary arteries. The MRCA results were more likely to agree with the consensus for definition of the proximal course of the coronary arteries (P<0.02). CONCLUSIONS: For the assessment of anomalous coronary artery anatomy in patients with congenital heart disease, the use of the combination of MRCA with x-ray coronary angiography improves the definition of the proximal coronary artery course. MRCA provides correct spatial relationships, whereas x-ray angiography provides a view of the entire coronary length and its peripheral run-off. Furthermore, respiratory-gated MRCA can be performed without breath holding and with only limited subject cooperation.

Adult↗

PubMed2000

Direct identification and quantitation of prednisone in the presence of overlapping hydrocortisone by liquid chromatography with electrospray and atmospheric-pressure chemical-ionisation mass spectrometry.

The paper describes the application of liquid chromatography interfaced to a triple quadrupole mass spectrometer utilising the multiple reaction monitoring (MRM) mode. The technique was shown to provide detection limits lower than 0.01% for the analysis of prednisone in the presence of hydrocortisone. Prednisone was mixed in concentrations from 0.500 to 0.0005 ppm (corresponding to 1% to 0.001% of the hydrocortisone concentration). These solutions were assayed using MRM observing the product ion transitions of 359.2-->147.1 and 359.2-->171.2 and was shown to be capable of detecting co-eluting impurities at concentrations of less than 0.001% of the major component. The assay of prednisone was shown to be linear over the range 0.500-0.0005 ppm with a correlation coefficient of 0.999 and a precision of 6.9% at the concentration of 0.005 ppm. The analysis was carried out using both atmospheric pressure chemical ionisation (APCI) and electrospray ionisation (ESI) as an interface. However, for these compounds APCI provided significantly more sensitive data compared to ESI.

Atmospheric Pressure↗

PubMed2000

A comparison between segmented k-space FLASH and interleaved spiral MR coronary angiography sequences.

A direct comparison of segmented fast low-angle short (FLASH) imaging and interleaved spiral magnetic resonance coronary angiography (MRCA) during free respiration using navigator echo has been performed. MRCA images were acquired in 30 normal subjects and 15 patients with coronary artery disease (CAD). Images of the right coronary artery were acquired during free respiration using navigator echo gating for both a segmented k-space FLASH sequence (8 views/segment, segment duration 105 msec) and an interleaved spiral sequence (20 interleaves, spiral read-out period 19 msec). Image quality was scored by three independent blinded observers, and coronary artery signal-to-noise ratio (SNR) and coronary artery/epicardial fat contrast-to-noise ratio (CNR) were measured. There was a significant improvement in image quality when coronary images were acquired with the interleaved spiral sequence (spiral 2. 3 vs. FLASH 1.8; P = 0.002). This was associated with an increase in the coronary artery SNR (16.6 +/- 6.9 vs. 11.8 +/- 5.0; P < 0.001), the coronary artery/epicardial fat CNR (12.5 +/- 6.1 vs. 7.4 +/- 4.0, P < 0.001), and the image resolution (256 x 256 vs. 256 x 128). However, there was a 12% increase in acquisition time for the interleaved spiral sequence. Image quality, SNR, CNR, and resolution can be improved using an interleaved spiral sequence. These improvements are secondary to the intrinsic characteristics of spiral imaging and the short acquisition period, which reduces the effects of both cardiac and respiratory motion.

Adult↗

PubMed2000

Left ventricular quantification in heart failure by cardiovascular MR using prospective respiratory navigator gating: comparison with breath-hold acquisition.

Cardiovascular magnetic resonance (CMR) is the reference standard for the assessment of cardiac function. Faster sequences, such as breath-hold (BH) fast low-angle shot, have made CMR more clinically acceptable and cost effective. In a significantly large patient group, however, holding their breath is difficult, resulting in poor-quality images. We compared prospective navigator-echo respiratory gating (NE), which allows image acquisition during free breathing, and BH imaging in 14 patients with heart failure and 10 normal volunteers. There was good agreement between both NE and BH volumes, mass, and ejection fraction. The image quality of both NE basal and apical slices was significantly better than the corresponding BH slices in both the heart failure (P < 0.01) and normal groups (P < 0.05). The NE image acquisition was more time efficient than the BH acquisition in the heart failure group (P < 0. 01), with no difference in the normal group (P = 0.2). Thus, prospective navigator-echo gating, previously only described in coronary artery imaging, can be used in the assessment of cardiac function. It is particularly useful in patients who find it difficult to hold their breath in whom NE provides good-quality, time-efficient images.

Electrocardiography↗

PubMed2000

Phase ordering with automatic window selection (PAWS): a novel motion-resistant technique for 3D coronary imaging.

Navigator acceptance imaging methods are hindered by the loss in scan efficiency which results from the changes in the breathing pattern of a subject over time. The diminishing variance algorithm (DVA), which does not use a predefined acceptance window, is less influenced by such changes. The use of phase ordering and weighting techniques has been shown to significantly improve image quality over nonordered window methods. However, the use of an acceptance window is inherent in all these techniques as a decision to accept or reject data must still be made. A technique is presented which is resistant to changes in breathing while allowing the use of phase ordering to provide effective motion artifact reduction in optimal time. The basic principle is described and illustrated for this automatic window-selection technique with in vitro results to demonstrate the feasibility of this method. Results of an in vivo study are also presented which demonstrate significant improvement in image quality over the DVA (p < 0.01) and hybrid-ordered phase encoding methods (p < 0.05).

Algorithms↗

PubMed2000

Interleaved spiral cine coronary artery velocity mapping.

Navigator-echo controlled interleaved spiral cine coronary-artery velocity maps were acquired in eight free-breathing volunteers. Good quality data were achieved in all subjects with phasic flow being clearly demonstrated. The improved efficiency of spiral k-space coverage compared to that of more conventional spin-warp techniques resulted in a mean scan time for 256 x 256 pixel-matrix studies of 94 sec (range 69 - 123 sec, SD = 20 sec), the navigator acceptance rate being typically 40-45%. Repeat scans in five subjects showed a high degree of reproducibility, with no significant differences occurring in the peak velocities (14.6+/-1.4 cm/sec vs. 14.5+/-1.5 cm/sec, P = ns) nor in the mean velocities measured over all cine phases (8.3+/-2.1 cm/sec vs. 8.7+/-1.6 cm/sec, P = ns). The potential benefits of using this sequence for assessing coronary blood flow and flow reserve are discussed. Magn Reson Med 43:787-792, 2000.

Blood Flow Velocity↗

PubMed1999

Magnetic resonance navigator echo diaphragm monitoring in patients with suspected diaphragm paralysis.

Real-time magnetic resonance (MR) navigator echo (NE) monitoring of the diaphragm is now possible. Using this technique, temporal changes in diaphragm position can be analyzed in a non-invasive fashion, without x-ray exposure. In this preliminary study, we have optimized three NE parameters (the NE column area, the NE repeat time, and the location of the NE on the diaphragm surface), and demonstrated the clinical application of MR NE diaphragm monitoring in patients with suspected diaphragm paralysis. The NE parameters were defined in 10 healthy volunteers, and diaphragm traces were scored for variance in NE diaphragm position registration. Using the optimal NE column parameters, we investigated four patients with diaphragm paralysis, one of whom required positive pressure ventilation while in the MR scanner, to show the utility of this technique. The NE diaphragm position registration was significantly affected by the area of the NE column, with poor position registration for the smallest column area (2.25 cm2 vs. 4 cm2 vs. 6.25 cm2, variance 6.3 vs. 0.6 vs. 0.3, P = 0.006). Diaphragm position registration was also significantly affected by the NE repeat time, with misregistration for the shortest repeat time (250 msec vs. 500 msec vs. 1000 msec, variance 11.9 vs. 0.6 vs. 1.0, P = 0.02), and data clipping, with loss of end-expiratory and end-inspiratory position registration, for the longest repeat time. Finally, if the NE was positioned too anteriorly, the diaphragm traces were of poor quality (anterior vs. dome vs. posterior, variance 11.8vs. 0.6vs. 3.2, P < 0.001). Application of the technique confirmed diaphragm paralysis in all four patients. The technique can be applied during positive pressure ventilation if necessary. The optimal NE parameters for diaphragm monitoring at 0.5 T were: column area, 400 mm2; NE repeat time; 500 msec; NE column positioned on the diaphragm dome. MR NE diaphragm monitoring provides a safe, non-invasive method of assessing diaphragm motion in patients with suspected diaphragm paralysis and may prove useful for long-term follow-up and monitoring of therapeutic interventions in these subjects.

Adult↗

PubMed1999

Safety and preliminary findings with the intravascular contrast agent NC100150 injection for MR coronary angiography.

In this Phase I clinical study, a novel ultrasmall superparamagnetic iron oxide contrast agent, NC100150 Injection (Nycomed Imaging, Oslo, Norway, a part of Nycomed Amersham), was used in two-dimensional magnetic resonance coronary angiography (MRCA). Safety and imaging data were acquired from 18 healthy male volunteers at both 0.5 and 1.5 T, before and after the administration of NC100150 Injection. Through-plane and in-plane images of the right coronary artery were analyzed. The postcontrast imaging sequences used prepulses and a high flip angle, to introduce T1 weighting. At 1.5 T (TE 2.6 msec), the through-plane coronary artery signal-to-noise ratio (SNR) (P = 0.04), coronary artery-to-fat signal difference-to-noise ratio (SDNR) (P = 0.001), coronary artery-to-myocardium SDNR (P<0.001), and coronary artery delineation (P<0.001) were improved by the administration of NC100150 Injection. For in-plane imaging, coronary artery delineation improved, but there were no significant changes in the SNR and SDNR. At 0.5 T, with the longer TE (6.7 msec) imaging sequence used, there was a reduction in the SNR (P = 0.01), the fat SDNR (through-plane P = 0.02; in-plane P = 0.25), and the coronary artery diameter (P<0.01 in both imaging planes). There was a trend toward improvement in the myocardial SDNR and coronary artery delineation. In conclusion, NC 100150 Injection was given safely to 18 healthy subjects, with no major adverse reactions. Coronary artery delineation was improved in both imaging planes at 1.5 T, with a trend toward improvement at 0.5 T. At 1.5 T, with a short TE imaging sequence, the marked T1 shortening effects of NC100150 Injection were dominant, leading to an improvement in the quantitative parameters for the through-plane images. At 0.5 T, with a longer TE imaging sequence, the T2* effects of the contrast agent played a role in reducing the quantitative image parameters. With further optimization of imaging sequences, to take advantage of the long-lived intravascular T1 shortening effect of NC100150 Injection, further improvements in MRCA will be possible.

Adult↗

PubMed1999

Differences between normal subjects and patients with coronary artery disease for three different MR coronary angiography respiratory suppression techniques.

A comparison between three magnetic resonance coronary angiography (MRCA) respiratory motion suppression techniques was performed for both normal subjects and patients with coronary artery disease (CAD). MRCA images were acquired in 17 normal subjects and 15 patients with CAD, using conventional breath-hold MRCA, navigator echo (NE)-guided breath-hold MRCA (LED feedback), and NE-gated MRCA during free respiration. Image quality, diaphragm registration, and total acquisition time were assessed. Overall, there was poor diaphragm registration for conventional breath-holding compared with free respiration (P < 0.001). CAD patients found it significantly more difficult to perform a steady breath-hold (P = 0.04) or attain the same diaphragm position over multiple breath-holds than normal subjects (P = 0.02). All normal subjects, but only 3 of the 15 CAD patients, were able to perform the LED feedback technique (P < 0.001). For normal subjects, image quality was similar between the three respiratory suppression techniques (P = 0.3), while for CAD patients there was an improvement in image quality, for images acquired during free respiration (breath-hold vs. free respiration, P < 0.01). There was no significant difference in the total acquisition times between the breath-hold and free respiration techniques (P = 0.2). There were substantial differences in the effectiveness of MRCA respiratory suppression techniques between normal subjects and CAD patients. In patients, only NE-gated MRCA performed well, requiring minimal cooperation with no increase in total acquisition time. Validation of NE-MRCA techniques should always be performed in patients, as well as normal subjects, to ensure correct evaluation of the technique for the target population.

Adult↗

PubMed1999

First-pass myocardial perfusion imaging and equilibrium signal changes using the intravascular contrast agent NC100150 injection.

In this phase I clinical study, the new ultrasmall superparamagnetic iron oxide contrast agent, NC100150 Injection (Nycomed AS, Oslo, Norway, a part of Nycomed Amersham), was assessed for first-pass magnetic resonance myocardial perfusion studies and its ability to produce equilibrium signal changes, as a possible indicator of myocardial blood volume. Data were acquired in 18 healthy male volunteers at 0.5 T and 1.5 T. At both field strengths, first-pass studies using T1-weighted sequences were acquired. Long TE spin-echo echoplanar imaging (EPI) was used at 0.5 T and short TE fast low-angle shot (FLASH) imaging at 1.5 T. With both sequences, T1 effects dominated the images for low doses, and time intensity curves potentially suitable for perfusion analysis were generated. At higher doses, T2 and T2* effects were observed. At 1.5 T, these predominantly affected the blood pool signal; however, at 0.5 T the myocardial signal was also involved, reflecting the relative T2 and T2* sensitivity of the spin-echo EPI sequence as a result of the long TE and long readout window, respectively. Equilibrium changes were assessed at both field strengths using T1-weighted FLASH sequences and in addition at 1.5 T using T2*-weighted gradient-echo EPI. With the T1-weighted images at both field strengths, signal changes were observed in all subjects; however, no dose-response relationship could be shown. With the T2*-weighted EPI there was significantly lower signal (P < 0.05) with the 3 and 4 mg/kg doses than with the 2 mg/kg dose. In conclusion, NC100150 Injection is useful for first-pass myocardial perfusion using T1-weighted sequences; however, low doses in combination with short TE sequences are required to minimize sensitivity to T2* effects. Equilibrium signal changes can also be induced in the myocardium. More work is required to optimize the imaging sequences and dose of NC100150 Injection for first-pass studies and also to determine whether the equilibrium signal changes can be used to measure myocardial blood volume changes in ischemic heart disease.

Adult↗

PubMed1999

Coronary artery imaging in a 0.5-Tesla scanner: implementation of real-time, navigator echo-controlled segmented k-space FLASH and interleaved-spiral sequences.

Coronary angiography techniques have been implemented on a 0.5-Tesla scanner with a view to performing coronary artery imaging. Slice-followed, segmented k-space FLASH sequences and interleaved-spiral sequences have been employed with acquisitions under real-time navigator echo control with patient feed back, enabling poor signal-to-noise levels to be overcome by averaging data acquired over multiple, variable-length, reproducible breath holds. Good-quality, millimetre-resolution coronary images were obtained in ten normal subjects with both techniques. The mean percent of data segments or interleaves acquired with the navigator echo within the 5-mm diaphragm acceptance window was 57% [standard deviation (S.D.), 11%; range, 38-85%], and the average image-acquisition times were 123+/-22 sec and 71+/-14 sec for segmented FLASH and interleaved-spiral imaging, respectively. In addition to shorter acquisition times, the interleaved-spiral sequence has superior temporal resolution, allowing the acquisition of limited, multislice data sets. However, the sequence is particularly sensitive to the off-resonance effects of residual epicardial fat surrounding the artery and to field nonuniformities, both of which lead to image blurring and, unlike segmented FLASH acquisitions (which are very robust), the spiral data sets generally require postprocessing.

Adult↗

PubMed1999

3D coronary artery imaging with phase reordering for improved scan efficiency.

Three-dimensional (3D) coronary imaging has the potential to overcome problems resulting from vessel tortuosity and to reduce partial volume effects. With these techniques, however, acquisition times are long and respiratory motion artifacts problematical. This work describes the development of a method that applies phase encode reordering to 3D acquisitions, allowing larger navigator acceptance windows to be used, with a consequent reduction in acquisition time. This method is compared with navigator acceptance window methods (the acceptance-rejection algorithm and the diminishing variance algorithm) and the retrospective respiratory gating technique, both in vitro and in vivo. The use of phase reordering with a 10 mm acceptance window provided a significant increase in scan efficiency over a non-reordered 5 mm method (P<0.001) with no significant change in image quality, and a significant increase in image quality compared with a non-reordered image acquired in the same time (P<0.05). A significant improvement in both image quality and scan efficiency was demonstrated over the retrospective respiratory gating method (P<0.05).

Adult↗

PubMed1999

Motion-selective encoding for fast cine imaging.

In magnetic resonance (MR) cine imaging applications, it is common that only a fraction of the field of view is used for delineating dynamic features whereas surrounding static structures are merely served as landmarks for three-dimensional orientation. This paper presents a method of using motion-selective encoding for fast cine imaging. By the use of a simple RF saturation pulse, the imaging field of view was divided into two areas, one with motion and the other without. This allowed the static material to be imaged by fast ungated acquisition and dynamic structures by reduced phase encoding. Issues related to phase error correction were addressed and the proposed algorithm was validated using images acquired from five normal subjects. The saving in imaging time was dependent on the size of the moving structures and a 35% reduction in imaging time did not cause visually noticeable changes in image quality. The application of the technique is limited to cine images with large surrounding static structures and a theoretical analysis of maximum savings in imaging time in relation to the size of the moving structures within the image field of view is provided. Magn Reson Med 42:430-435, 1999.

Adult↗

PubMed1998

New helper cells and matched early region 1-deleted adenovirus vectors prevent generation of replication-competent adenoviruses.

The presence of replication-competent adenoviruses (RCAs) in batches of replication-defective adenovirus (Ad) vectors is a major problem for the application of these vectors in gene therapy. RCAs are generated by recombination between sequences in the Ad vector and homologous Ad sequences in the helper cells, resulting in the acquisition by the vector of early region 1. To prevent the formation of RCAs, we have developed helper cell lines, which we named PER, and matched Ad vectors that do not have sequence overlap. PER cells contain the Ad serotype 5 (Ad5) E1A- and E1B-encoding sequences (Ad5 nucleotides 459-3510) under the control of the human phosphoglycerate kinase (PGK) promoter. We demonstrate that PER cells synthesize high levels of the Ad5 E1A and E1B proteins. The yields from PER cells of E1-deleted Ads are similar to those obtained from earlier helper cells, such as 911 and 293 cells. Propagation of matched Ad vectors, which lack Ad5 nucleotides 459-3510, in one of the PER clones, PER.C6, does not result in the generation of RCAs, in contrast to propagation in 293 cells. We conclude that the combination of PER.C6 cells and nonoverlapping E1-deleted adenoviral vectors eliminates the problem of RCA generation by homologous recombination, and allows cost-effective production of safe, clinical-grade batches of recombinant Ad vectors.

Adenovirus E1A Proteins↗

PubMed1998

Three-dimensional coronary MR angiography using zonal echo planar imaging.

Using an adapted two-dimensional spatially selective RF excitation scheme, a novel yet practical three-dimensional (3D) zonal echo-planar imaging technique for MR coronary angiography has been developed. The robustness of the technique compared with the two-dimensional (2D) segmented fast low angle shot (FLASH) method was evaluated using the right coronary artery images of 16 asymptomatic volunteers with a 0.5-T mobile scanner. Each 3D acquisition required multiple breath-holds, and real-time navigator echoes were used to ensure consistent breath-holding. Advantages of the technique include an improved signal-to-noise ratio, clearer depiction of tortuous coronary vessels due to decreased partial volume effects, and reduced motion blurring by the use of a short echo-planar readout.

Adult↗

PubMed1998

Community-based mental health care: bridging the gap between community care and primary care.

Australian nursing is undergoing major changes in practice, education and research in a climate of burgeoning health-care costs, and changing priorities and service directions. The government is searching for new ways to deliver services that are appropriate and equitable while focusing on containing costs. These are signs that it is an opportune time for nurses to test new roles, and one suggested way to provide extra cost-effective service is through the use of nurse practitioners. In order to improve the delivery of mental health services, the nurse practitioner specializing in mental health can provide a link between the community and the primary care provided by general practitioners. A proposed model for nurse practitioners in mental health is presented as a means of bridging this gap.

Community Health Nursing↗

PubMed1997

Non-breath-hold lung magnetic resonance imaging with real-time navigation.

Magnetic resonance imaging (MRI) with navigating techniques based on consecutive breath-holds demand a level of respiratory control that is often beyond the capability of patients with lung disease. The objectives of this investigation were to develop and evaluate a navigating technique for lung MRI that does not rely on patient cooperation. Navigating techniques were implemented at 0.5 T using conventional imaging techniques of short echo-time and imaging during normal breathing in the diastolic phase of the cardiac cycle. A column of spins, orthogonal to the diaphragm, was excited both immediately before and after the imaging segment. These signals were processed in real time to provide the position of the lung-diaphragm interface. An imaging segment was considered correctly acquired only when the interface position was within the acceptance window both before and after the acquisition of the segment. A distribution of lung-diaphragm interface positions obtained during normal respiration was employed to define the acceptance window. In the case of multislice techniques, the position of the lung-diaphragm interface immediately before the imaging segment was also employed to decide which phase-encoding step to acquire next, therefore reducing the apparent frequency of the respiratory motion. A distribution of interface positions, updated in real time, served as a reference for the allocation of phase-encoding steps according to diaphragm position. The lung images obtained represent a significant advance in image quality, improving further the ability of MR to detect and monitor pulmonary disease. Motion artifacts were reduced, and images reliably demonstrated smaller vessels, which are not normally visible without navigation.

Computer Systems↗