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Biomedical subjects

P Glover

Publications and source records attributed to P Glover.

At least 37 records · Page 2Linked to original sources
PubMed1995

An assessment of the intrauterine sound intensity level during obstetric echo-planar magnetic resonance imaging.

In order to assess the sound level experienced by the fetal ear during obstetric magnetic resonance imaging, a fluid filled stomach was used as an experimental model of the gravid uterus. A better than 30 dB attenuation in intensity was recorded across the frequency band of interest for all patient orientations. This was enough to reduce acoustic sound pressure from a level close to the instantaneous damage threshold (120 dB), to an acceptable level (< 90 dB). Direct mechanical coupling through the patient table was also shown to increase uterine sound pressure levels by as much as 10 dB. Much higher peak pressures could be obtained by tapping of abdomen with the fingers.

Acoustics↗
PubMed1995

An educational intervention to increase faculty publication productivity.

BACKGROUND: Writing is an essential skill for academic family physicians. It is essential in all of the academic physicians' roles, and publications are critical for promotion and tenure. This study describes a three-part faculty development instructional program designed to teach writing skills. The instructional program was repeated over a 3-year period involving two different institutions with departments of family medicine. METHODS: Educational interventions included seminars, workshops, and independent practice, with feedback from senior advisors. The practice and feedback sections centered on the faculty members' own written products. RESULTS: This series resulted in the publication of 16 papers from 13 of the 40 faculty participants. CONCLUSIONS: Our experience suggests that a writing series is one effective method that departments of family medicine may use to facilitate the writing productivity of faculty.

Authorship↗
PubMed1994

Potent clastogenicity of the human carcinogen etoposide to the mouse bone marrow and mouse lymphoma L5178Y cells: comparison to Salmonella responses.

The suspect human carcinogen, etoposide, is known to be genotoxic, producing both gene and chromosomal mutations, probably by virtue of its ability to inhibit topoisomerase II activity. The present paper describes assays conducted using the Salmonella assay, the mouse lymphoma tk+/- assay (gene and chromosomal mutation analysis and molecular analysis of tk-/- mutants) and the mouse bone marrow micronucleus assay. Nonreproducible, weak, dose-related increases in mutation frequency in strain TA98 (but not TA1538 or TA1537) of Salmonella typhimurium were observed. Etoposide was highly mutagenic at the heterozygous thymidine kinase (tk+/-) locus of L5178Y mouse lymphoma cells at concentrations below 0.1 micrograms/ml. Mostly small colony mutants were induced, consistent with the potent clastogenicity also observed. Molecular analysis of mutants indicated that 83% and 92% of large and small colony mutants, respectively, had lost the entire target gene sequence. Chromosomally aberrant L5178Y cells were approximately 2 to 600-fold more prevalent than small tk-/- mutant colonies. This suggests that the viable target for etoposide-mediated clastogenesis in the selective assay is approximately one-fifth of chromosome 11b, itself being approximately one-fortieth of the mouse genome. An unusually potent response was observed for etoposide in the mouse bone marrow micronucleus assay (63.1 +/- 18 MPE/1,000 PE 24 hours after an oral dose of 1 mg/kg). The minimum detectable dose level in the assay was between 0.01 and 0.1 mg/kg. At dose levels between 1 and 15 mg/kg, an inverse dose response was observed. This reduction in assay response was not due to the small concommitant decrease in the incidence of polychromatic erythrocytes, a conclusion based on studies with N-methyl-N-nitrosourea. Animals sampled 48 hours after dosing with etoposide (10 mg/kg) had no polychromatic erythrocytes in the bone marrow. These observations for the micronucleus assay await explanation. The chemical structure of etoposide is displayed and discussed within the context of such strong mutagenic activity being associated with a nonelectrophilic agent.

Animals↗
PubMed1991

RF cavity resonator and split-resonator designs.

A simple high-pass cavity resonator has been constructed for NMR imaging use at 500 MHz. A capacitative circuit arrangement is used to drive the device. A novel split-coil or half-resonator design is also introduced for lower-frequency operation with applications in whole-body medical imaging.

Equipment Design↗
PubMed1991

Mutagenicity of 2-amino-N6-hydroxyadenine (AHA) at three loci in L5178Y/tk+/- mouse lymphoma cells: molecular and preliminary cytogenetic characterizations of AHA-induced tk-/- mutants.

2-Amino-N6-hydroxyadenine (AHA) is a remarkably efficient and specific inducer of point mutations in Neurospora, with few or no larger scale events being detected (de Serres et al., 1985). In the present studies, AHA is shown to be a potent point mutagen at the tk +/-, hprt+ and Na+/K+ ATPase loci in L5178Y/tk (+/-)-3.7.2C mouse lymphoma cells. Both large and small colony tk-/- mutants were analyzed at the molecular level and a preliminary assessment was made of small colony mutant karyotypes (230 bands/haploid metaphase cell; large colony mutants typically have normal karyotypes and were not analyzed). AHA induced greatly delayed (7-9 cell doublings) cytotoxicity, suggestive of a mutational mechanism (e.g., base-pair substitution) requiring DNA replication prior to its phenotypic expression. Approximately one-third of the tk -/- mutants formed small colonies, a phenotype which is typically associated with alterations to chromosome 11b, the site of the functional tkb allele in the parental cells. However, banded karyotypes have provided convincing evidence for alterations chromosome 11b in only 2 of the 7 small colony mutants analyzed. Southern blot analysis showed that 78% (21/27) of these small colony mutants have retained the Nco-1 6.3-kb band, which is diagnostic of the tkb allele. This makes AHA unique among the mutagens examined so far in inducing small colony mutants without inducing large losses of tkb DNA. Although a dose-dependent increase in the proportion of small colony mutants was noted, no significant dose-dependent differences were seen at the molecular level in the relatively few mutants analyzed. The majority of AHA-induced tk -/- mutants formed large colonies. Southern blot analysis showed that 86% (25/29) of these had retained the Nco-1 6.3-kb band which is diagnostic of the tkb allele. It is concluded that AHA induces primarily micromutations (less than 100 base pairs), probably through a base-pair substitution mechanism, at the tk, hprt and Na+/K+ ATPase loci in this system, with some larger scale damage (kilobases of DNA at the molecular level; chromosome 11b damage at the cytogenetic level) also occurring.

Adenine↗
PubMed1990

Molecular aspects of chemical mutagenesis in L5178Y/tk +/- mouse lymphoma cells.

Southern blot analyses were performed on DNA from at least 10 large and 10 small colony thymidine kinase-deficient (tk -/-) mutants induced by each of 10 mutagens [2-amino-N6-hydroxyadenine (AHA), ethyl methanesulfonate (EMS), methyl methanesulfonate, 2-acetylaminofluorene, methotrexate, caffeine, methapyrilene, 4-(9-acridinylamino)-methanesulfo-m-anisidide, hycanthone methanesulfonate and procarbazine]. Two molecular mutant genotypes were recognized upon digestion with NcoI and subsequent probing with a 1.1 kb cDNA insert from plasmid pMtk 4: (i) no detectable alteration, and (ii) the absence of the functional tkb allele as indicated by the absence of the 6.3 kb fragment. In combination with the previously established chromosomal nature of most small colony tk -/- mutants, this permitted the classification of these 10 mutagens according to the relative proportions of each of four classes of genetic damage they induced. AHA and EMS gave mutational spectra consistent with their point mutational effects in other systems. The other eight mutagens induced mostly small colony mutants, most of which had lost the entire original tkb allele. Methotrexate induced high frequencies of large colony mutants at the tk locus, most of which lacked the tkb allele, although it is weakly or non-mutagenic at the hemizygous hprt locus in these same cells. At least three of these mutagens-methotrexate, caffeine, methapyrilene (and possibly procarbazine)--lack structural alerts for DNA reactivity, implying a major class of non-DNA primary targets for mutagenicity in mammalian cells that interact secondarily with the chromosome. These results are discussed in relation to the known differences in sensitivity among various short-term tests for genotoxicity.

Animals↗
PubMed1990

Estimation of lung volume in infants by echo planar imaging and total body plethysmography.

Echo planar imaging (an extremely fast method of magnetic resonance imaging) was used to measure lung volume in a group of nine infants, all of whom had had respiratory problems. The mean echo planar imaging estimate of total lung volume was 44 +/- 9 ml/kg. In each case the right lung was larger than the left (ratio 52.8:47.2%). The mean thoracic gas volume was 36 +/- 8 ml/kg. The entire sequence of images of the thorax (about 400) takes five minutes to complete, infants require no sedation, and there are no side effects.

Female↗
PubMed1989

Snapshot imaging at 0.5 T using echo-planar techniques.

Echo-planar imaging using a magnetic field strength of 0.5 T has resulted in an improvement in image quality compared with recent images published at 0.1 T. The sensitivity of the technique to main magnetic field inhomogeneity and transient eddy currents has necessitated innovations in gradient and radiofrequency coil design. These improvements are described, and new variations in the echo-planar pulse sequence which provide better contrast and allow separate imaging of water and fat distributions are presented.

Abdomen↗
PubMed1989

Whole-body echo-planar MR imaging at 0.5 T.

The ultra-high-speed echo-planar imaging technique produces instant snapshot magnetic resonance images in exposure times ranging from approximately 10 to 100 msec. A particular variant, the modulus blipped echo-planar single-pulse technique (MBEST), possesses two advantages: First, it makes the technique experimentally more robust; second, it introduces inherent T2 weighting in the images. The authors have used MBEST with an exposure time of 64 msec to explore the potential range of clinical applications in a series of normal volunteers. Applications include evaluation of the heart, renal function, and gastrointestinal tract. All images were obtained with proton resonances at 22 MHz.

Abdomen↗
PubMed1988

Improvements in snap-shot nuclear magnetic resonance imaging.

New variants of the ultra-high-speed echo-planar imaging technique have been used to obtain snap-shot images of adult patients and volunteers at 0.1 T. Modified pulsed-gradient sequences together with non-linear signal sampling and activity screened gradients have greatly improved the image quality obtainable by single-shot methods. A particular variant, modulus blipped echo-planar single-pulse technique (MBEST), although slightly slower than the blipped echo-planar single-pulse technique (BEST), is experimentally more robust and incorporates intrinsic T2 weighting. An account of these improvements together with some experimental results is presented.

Adult↗
PubMed1987

Real-time movie imaging from a single cardiac cycle by NMR.

Using a 1-m-bore superconductive magnet at 0.1 T, whole-body transverse images through adult humans have been obtained at repetition times of 57 ms. The techniques used were minor variations of echo-planar imaging (EPI) employing large pulsed gradients to provide complete coverage of the plane in phase space, and low-angle RF excitation sequences allowing rapid repetition of the experiment. In addition active magnetic screening of the gradient coils was implemented to protect the surrounding magnet from the eddy currents induced by the necessarily fast switching of the large gradient fields.

Adult↗