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Biomedical subjects

E Ramsay

Publications and source records attributed to E Ramsay.

16 recordsLinked to original sources

Adaptive bilateral breast MRI using projection reconstruction time-resolved imaging of contrast kinetics.

PURPOSE: To introduce a bilateral implementation of an adaptive imaging technique in which both dynamic and high resolution breast MR images are acquired simultaneously. MATERIALS AND METHODS: Adaptive three-dimensional bilateral breast imaging in the sagittal plane was achieved by combining two elements: a projection reconstruction time-resolved imaging of contrast kinetics (PR-TRICKS) k-space trajectory and a slab interleaved sequence that imaged alternate breasts every TR. A pilot study was performed to evaluate image quality and contrast uptake behavior, using eight patients with previously identified benign lesions. RESULTS: Adaptive reconstruction demonstrated breast lesions in all eight women with similar image quality and signal-to-noise ratio (SNR) to Cartesian images with comparable imaging parameters. Contrast enhancement curves covering the entire postinjection time period were obtained from the dynamic images and in one case compared to previous enhancement profiles from a conventional Cartesian trajectory. CONCLUSION: Bilateral dynamic and high spatial resolution images with high SNR can be achieved in a clinically feasible manner, providing both kinetic and morphologic analysis with a single data set. This may obviate the need for multiple MRI examinations for a thorough breast MRI workup.

Artifacts↗

Development and assessment of conventional and targeted drug combinations for use in the treatment of aggressive breast cancers.

Combination chemotherapy has been at the forefront of cancer treatment for over 40 years. However, the rationale for selecting drug combinations and the process used to demonstrate clinical effectiveness has primarily followed trial and error methodology. Typically, the selection and assessment of combined drug therapies has been based on the effectiveness of each agent as monotherapy in treating the neoplasm and avoiding overlapping toxicities, followed by clinical trials to establish dose scheduling, toxicity, and efficacy. Unfortunately, this scheme is inefficient in terms of the time required to complete and revise these clinical trials based on the outcome to optimize the drug combination. A more rational approach for the development of combination oncology products should consider (i) in vitro assays for assessing therapeutic effects of drug combinations (antagonistic, additive or synergistic interactions) when added simultaneously; (ii) methods for measuring these interactions in vivo; (iii) the importance of understanding pharmacokinetic and biodistribution parameters when using drug combinations; (iv) the need to assess pathways known to contribute to cancer cell survival as well as metastasis; and (iv) the need to assess the fate of different cell populations (cancer and stroma) contributing to the development of cancer. Therefore, the goal of this article is to provide a road map for the preclinical development of drug combination products that will have improved therapeutic activity and a high likelihood of providing beneficial therapeutic outcomes in patients with aggressive cancers with a specific focus on patients with breast cancer.

Animals↗

Two-photon optical-beam-induced current solid-immersion imaging of a silicon flip chip with a resolution of 325 nm.

We report high-resolution subsurface imaging of a silicon flip chip by detection of the photocurrent generated by the two-photon absorption of 1530-nm light from a femtosecond Er:fiber laser. The technique combines the focal sensitivity of two-photon excitation with the enhanced optical resolution of high-numerical-aperture solid-immersion imaging. Features on a sub-1-microm scale are clearly resolvable with high contrast, showing a resolution of 325 nm.

Journal Article↗

Polylysine and polyornithine gene transfer complexes: a study of complex stability and cellular uptake as a basis for their differential in-vitro transfection efficiency.

Gene transfer vectors formed between the cationic polyamino acid, poly-(L)-omithine (PLO) and plasmid DNA (pDNA) have demonstrated superior transfection efficiency (up to x 10-fold) compared to equivalent polylysine-based systems in-vitro. The mechanism(s) underlying this observation remains to be elucidated. We previously reported no significant difference in colloidal particle size or zeta potential of polycation/pDNA complexes formed with poly-(L)-lysine (PLL), poly-(D)-lysine (PDL) or PLO. Here we report spectrofluorometric analysis indicating that PLO condenses pDNA at lower charge (+/-) ratios than PLL or PDL (cf. 0.8:1, 1.2:1 and 1.5:1). Moreover, PLO/pDNA complexes proved more stable to disruption by the polyanions, poly-(L)-aspartic acid (PAA) and heparin. There were no qualitative differences in the ability of the polycations to protect complexed pDNA from enzymatic degradation both in the presence and in the absence of polyanions. The superior transfection efficiency of PLO/pDNA complexes did not appear to be mediated by an increased cellular delivery of pDNA. The data suggests a greater affinity of PLO for pDNA as an important parameter for the observed superior in-vitro transfection efficiency.

Cell Line↗

Comparison of breast magnetic resonance imaging, mammography, and ultrasound for surveillance of women at high risk for hereditary breast cancer.

PURPOSE: Recommended surveillance for BRCA1 and BRCA2 mutation carriers includes regular mammography and clinical breast examination, although the effectiveness of these screening techniques in mutation carriers has not been established. The purpose of the present study was to compare breast magnetic resonance imaging (MRI) with ultrasound, mammography, and physical examination in women at high risk for hereditary breast cancer. PATIENTS AND METHODS: A total of 196 women, aged 26 to 59 years, with proven BRCA1 or BRCA2 mutations or strong family histories of breast or ovarian cancer underwent mammography, ultrasound, MRI, and clinical breast examination on a single day. A biopsy was performed when any of the four investigations was judged to be suspicious for malignancy. RESULTS: Six invasive breast cancers and one noninvasive breast cancer were detected among the 196 high-risk women. Five of the invasive cancers occurred in mutation carriers, and the sixth occurred in a woman with a previous history of breast cancer. The prevalence of invasive or noninvasive breast cancer in the 96 mutation carriers was 6.2%. All six invasive cancers were detected by MRI, all were 1.0 cm or less in diameter, and all were node-negative. In contrast, only three invasive cancers were detected by ultrasound, two by mammography, and two by physical examination. The addition of MRI to the more commonly available triad of mammography, ultrasound, and breast examination identified two additional invasive breast cancers that would otherwise have been missed. CONCLUSION: Breast MRI may be superior to mammography and ultrasound for the screening of women at high risk for hereditary breast cancer.

Adult↗

Diagnosis and management of a patent urachus in a white rhinoceros calf (Ceratotherium simum simum).

A 10-day-old female southern white rhinoceros calf (Ceratotherium simum simum) was diagnosed with a patent urachus after urine was observed dribbling from the umbilicus. After being separated from its mother, the animal was sedated with i.m. butorphanol and anesthetized with isoflurane in oxygen for surgical correction of the patent urachus. Mild postoperative complications involved seroma formation and partial skin incision dehiscence, which necessitated three follow-up immobilizations for reevaluation and treatment of the surgical site. Histopathology did not reveal an infectious etiology as the cause for the complications or for the patent urachus. The etiology of the patent urachus in this animal remains undetermined. This report represents the first documented case of a patent urachus in a white rhinoceros.

Animals↗

Examination of the biophysical interaction between plasmid DNA and the polycations, polylysine and polyornithine, as a basis for their differential gene transfection in-vitro.

The impetus to develop non-viral gene delivery vectors has led to examination of synthetic polycationic polymers as plasmid DNA (pDNA) condensing agents. Previous reports have highlighted superiority (up to x 10-fold) in the in-vitro transfection of pDNA complexes formed by poly-(L)-ornithine (PLO) compared to those formed with poly-(L)-lysine (PLL). The apparent basis for this consistent superiority of PLO complexes remains to be established. This comparative study investigates whether physico chemical differences in the supramolecular properties of polycation:pDNA complexes provide a basis for their observed differential gene transfection. Specifically, particle size distribution and zeta potential of the above complexes formulated over a wide range of polycation:pDNA ratios were found to be consistent with a condensed (150-200 nm) cationic ( + 30-40 mV) system but not influenced by the type of cationic polymer used. A spectrofluorimetric EtBr exclusion assay showed that polycation:pDNA complexes display different pDNA condensation behaviour, with PLO able to condense pDNA at a lower polycation mass compared to both polylysine isomers, and form complexes that were more resistant to disruption following challenge with anionic counter species, i.e. poly-(L)-aspartic acid and the glycosaminoglycan molecule. heparin. We conclude that particle size and surface potential as gross supramolecular properties of these complexes do not represent, at least in a non-biological system, the basis for the differential transfection behaviour observed between these condensing polymers. However, differences in the ability of the polylysine and polyornithine polymers to interact with pDNA and to stabilise the polymer-pDNA assembly could have profound effects upon the cellular and sub-cellular biological processing of pDNA molecules and contribute to the disparity in cell transfection efficiency observed between these complexes.

Adenocarcinoma↗

Field immobilization of muskrats (Ondatra zibethicus) for minor surgical procedures.

A combination of ketamine hydrochloride and xylazine hydrochloride at doses of 50 mg/kg and 5 mg/kg, respectively, was used to immobilize 48 muskrats (Ondatra zibethicus) from October 1993 to November 1994 in Tennessee (USA). Mean (+/-SD) time for induction was 2.97 +/- 1.1 min. After a mean (+/-SD) duration of 27.2 +/- 3.5 min intramuscular yohimbine hydrochloride at a dose of 0.125 mg/kg was administered. Mean (+/-SD) recovery time was 48.1 +/- 21.6 min. All anesthetic inductions were smooth and sufficient depth of anesthesia was achieved to allow surgical collection of adipose tissue. Recovery times were more variable than expected. There was a significant (P < or = 0.05) drop in heart rate, respiratory rate, and body temperature during anesthesia. One animal died during recovery.

Anesthetics, Dissociative↗

Herpesvirus particles associated with oral and respiratory lesions in a California desert tortoise (Gopherus agassizii).

A 60-year-old captive California desert tortoise (Gopherus agassizii) which died in August 1990 at the University of California, Davis, California (USA), during treatment for colonic impaction had marked caseous necrosis of the oral cavity, choana, trachea, and lungs. Numerous intranuclear inclusion bodies and a large number of syncytial giant cells were seen in the oral cavity and respiratory tract along with bacterial granulomas. Pasteurella testudinis, Streptococcus veridans, and coagulase-negative Staphilococcus spp. were cultured from the lesions. Using electron microscopy, herpesvirus particles were observed in intranuclear inclusions and cytoplasm. Viral stomatitis, tracheitis, and bronchopneumonia complicated by bacterial infection were diagnosed. Although respiratory disease is common in desert tortoises, this is believed to be the first report of association with a viral infection.

Animals↗

Effect of flunixin meglumine and cimetidine hydrochloride on the pH in the third compartment of the stomach of llamas.

A Tigon fistula was surgically implanted into the third compartment of the stomach of 5 llamas to allow measurement of gastric pH. The llamas were allotted into 2 groups and given flunixin meglumine or cimetidine hydrochloride for 3 days. After 4 days without treatment, the drugs given to each group were reversed. Measurements of gastric pH were taken every 30 minutes for 6 hours, using an automated pH meter. The pH measurements after drug administration were compared with measurements obtained during a pretreatment control period. Gastric pH during pretreatment control periods had a mean of 1.43 +/- 0.063 (mean +/- SE). The use of flunixin did not significantly decrease gastric pH, compared with pretreatment controls. Gastric pH was significantly higher within the first 30 minutes after administering cimetidine, compared with pretreatment controls, but this difference disappeared at all later times.

Animals↗

Effect of the cyclopyrrolones suriclone and RP 59037 on body temperature in mice.

The effects of the cyclopyrrolones suriclone and RP 59037 on body temperature were investigated in male TO mice. The full agonist suriclone (3, 10, 30 mg/kg i.p.) produced significant hypothermia which was inhibited by concurrent administration of benzodiazepine receptor antagonists of both benzodiazepine (flumazenil; 10 mg/kg i.p.) and beta-carboline (ZK 93426; 3 mg/kg i.p.) structure. The response to suriclone (10 mg/kg i.p.) was also attenuated by benzodiazepine (Ro 17-1812; 10 mg/kg i.p.) and beta-carboline (ZK 91296; 30 mg/kg i.p.) partial agonists - which have no effect on body temperature per se. In contrast with these compounds, the cyclopyrrolone partial agonist RP 59037 (10, 30 mg/kg i.p.) produced significant hypothermia itself (although it was much less efficacious in this respect than the full agonist) and at a dose of 30 mg/kg failed to block the decrease in body temperature induced by suriclone (10 mg/kg i.p.). Thus suriclone acts as a full agonist at benzodiazepine receptors in the body temperature paradigm. RP 59037 possesses some partial agonist properties in this model, however, it appears to have greater intrinsic activity than other partial agonists tested previously.

Analysis of Variance↗

Attenuation of the behavioural effects of ethanol in mice by des-enkephalin-gamma-endorphin (ORG 5878).

This study shows inhibition of the increase in locomotor activity induced by ethanol (2 g/kg i.p.) in mice by a low dose (0.1 mg/kg i.p.) of the non-opioid beta-endorphin fragment ORG 5878 (des-enkephalin-gamma-endorphin). ORG 5878 (0.1 mg/kg i.p.) also significantly antagonised the large increase in electroshock seizure threshold produced by ethanol (1.5 g/kg i.p.). In contrast, the hypothermia induced by ethanol (2 g/kg i.p.) was not altered by ORG 5878 (0.1 mg/kg i.p.). The effects of ORG 5878 showed an abnormal dose-response relationship, in that a high dose (1 mg/kg i.p.) did not significantly suppress any of the behavioural effects of ethanol examined although there was some indication that it attenuated the stimulant action of ethanol. ORG 5878 (0.1, 1 mg/kg i.p.) did not have any intrinsic effects on locomotion, seizure threshold or body temperature in mice. These results are the first demonstration that ORG 5878 may act as an ethanol antagonist in some paradigms.

Animals↗