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Biomedical subjects

R Giles

Publications and source records attributed to R Giles.

At least 19 recordsLinked to original sources
PubMed2006

Outcome after complete percutaneous removal of infected pacemaker systems and implantable cardiac defibrillators.

The mortality of retained, infected pacemaker systems is high. We assessed the safety and rate of relapse of infection after complete percutaneous removal of leads of infected pacemaker systems. None of the 40 subjects experienced procedure-related mortality and there were no cases of relapse after a median duration of follow up of 8 years (range, 3 months to 12 years). Procedure-related complications and other adverse events during therapy are reported. Percutaneous removal of infected pacemakers in conjunction with appropriate antibiotic therapy is safe and effective.

Adult↗
PubMed2005

Funisitis associated with leptospiral abortion in an equine placenta.

Funisitis, inflammation of the umbilical cord, is well recognized in human placentas. This report describes a case of funisitis associated with leptospiral infection in the placenta of a Thoroughbred foal born prematurely. The umbilical cord had diffuse superficial yellow discoloration along its entire length. Microscopic evaluation showed an exudate of neutrophils admixed with fibrin on the surface. Warthin-Starry staining showed spirochetes in the Wharton's jelly of the umbilical cord. A locally extensive, severe placentitis not involving the star and allantoic cystic hyperplasia were the other lesions observed in the allantochorion. Leptospira funisitis is similar to the funisitis of congenital syphilis in humans, although there are some major microscopic differences. In Leptospira funisitis, lesions were limited to the cord surface, whereas in lesions in human umbilical cords with Treponema pallidum infection, the changes are observed mostly around the vessels and in the Wharton's jelly.

Abortion, Veterinary↗
PubMed2001

STR primer concordance study.

Over 1500 population database samples comprising African Americans, Caucasians, Hispanics, Native Americans, Chamorros and Filipinos were typed using the PowerPlex 16 and the Profiler Plus/COfiler kits. Except for the D8S1179 locus in Chamorros and Filipinos from Guam, there were eight examples in which a typing difference due to allele dropout was observed. At the D8S1179 locus in the population samples from Guam, there were 13 examples of allele dropout observed when using the Profiler Plus kit. The data support that the primers used in the PowerPlex 16, Profiler Plus, and COfiler kits are reliable for typing reference samples that are for use in CODIS. In addition, allele frequency databases have been established for the STR loci Penta D and Penta E. Both loci are highly polymorphic.

Alleles↗
PubMed2001

The pattern of melatonin secretion is rhythmic in the domestic pig and responds rapidly to changes in daylength.

The aim of the study was to investigate the capability of pigs to respond to abrupt changes in lighting conditions by means of alterations in circadian melatonin profiles. Sixteen pre-pubertal crossbred male pigs weighing 40-45 kg were housed in individual pens in four temperature- and lighting-controlled climate rooms (four pigs per room). In two rooms there was a light-dark cycle of 16 L:8 D (Group A) and in two other rooms 8 L:16 D (Group B). Under both lighting regimens light intensity at pig eye-level was 220-240 lx during the light phase and less than 7 lx (red light) during the dark phase. The lighting regimens were changed after 2 wks to the opposite regimen and the change was repeated after a further 2 wks, so that animals ended up with the same light cycle with which they started. Blood was sampled at 2-hr intervals for 48 hr spanning each time of change in lighting. A further 24-hr sampling was performed at the end of the experiment (2 wks after the last change) in both groups and 1 wk after the change from short to long day lighting in Group A. On 83/86 occasions, pigs exhibited a clear circadian rhythm in plasma melatonin under both lighting regimens. Pigs responded immediately to the change from long to short day lighting by advancing melatonin secretion to the earlier lights-off time and some pigs were able to extend secretion to the delayed lights-on time. For short to long day changeover there was a small immediate response, with secretion pattern following the previously entrained endogenous rhythm to within 3 hr of the previous lights-on time. After 1 wk commencement of secretion was delayed by up to 2 hr, while after 2 wks some pigs were able to delay commencement of secretion until lights-off or to cease at lights-on. It is concluded that the domestic pig is able to commence adjustment to abrupt changes in photoperiod within a 1-wk acclimatization by altering circadian melatonin secretion. The present study suggests that it may be possible to use simplified lighting regimens instead of stepwise changing lighting programs in commercial piggeries to reduce the influence of season on production.

Animals↗
PubMed1998

Cytosine deaminase adenoviral vector and 5-fluorocytosine selectively reduce breast cancer cells 1 million-fold when they contaminate hematopoietic cells: a potential purging method for autologous transplantation.

Ad.CMV-CD is a replication incompetent adenoviral vector carrying a cytomegalovirus (CMV)-driven transcription unit of the cytosine deaminase (CD) gene. The CD transcription unit in this vector catalyzes the deamination of the nontoxic pro-drug, 5-fluorocytosine (5-FC), thus converting it to the cytotoxic drug 5-fluorouracil (5-FU). This adenoviral vector prodrug activation system has been proposed for use in selectively sensitizing breast cancer cells, which may contaminate collections of autologous stem cells products from breast cancer patients, to the toxic effects of 5-FC, without damaging the reconstitutive capability of the normal hematopoietic cells. This system could conceivably kill even the nondividing breast cancer cells, because the levels of 5-FU generated by this system are 10 to 30 times that associated with systemic administration of 5-FU. The incorporation of 5-FU into mRNA at these high levels is sufficient to disrupt mRNA processing and protein synthesis so that even nondividing cells die of protein starvation. To test if the CD adenoviral vector sensitizes breast cancer cells to 5-FC, we exposed primary explants of normal human mammary epithelial cells (HMECs) and the established breast cancer cell (BCC) lines MCF-7 and MDA-MB-453 to the Ad.CMV-CD for 90 minutes. This produced a 100-fold sensitization of these epithelial cells to the effects of 48 hours of exposure to 5-FC. We next tested the selectivity of this system for BCC. When peripheral blood mononuclear cells (PBMCs), collected from cancer patients during the recovery phase from conventional dose chemotherapy-induced myelosuppression, were exposed to the Ad.CMV-CD for 90 minutes in serum-free conditions, little or no detectable conversion of 5-FC into 5-FU was seen even after 48 hours of exposure to high doses of 5-FC. In contrast, 70% of 5-FC was converted into the cytotoxic agent 5-FU when MCF-7 breast cancer cells (BCCs) were exposed to the same Ad.CMV-CD vector followed by 5-FC for 48 hours. All of the BCC lines tested were shown to be sensitive to infection by adenoviral vectors when exposed to a recombinant adenoviral vector containing the reporter gene betagalactosidase (Ad.CMV-betagal). In contrast, less than 1% of the CD34-selected cells and their more immature subsets, such as the CD34+CD38- or CD34(+)CD33- subpopulations, were positive for infection by the Ad.CMV-betagal vector, as judged by fluorescence-activated cell sorting (FACS) analysis, when exposed to the adenoviral vector under conditions that did not commit the early hematopoietic precursor cells to maturation. When artificial mixtures of hematopoietic cells and BCCs were exposed for 90 minutes to the Ad.CMV-CD vector and to 5-FC for 10 days or more, a greater than 1 million fold reduction in the number of BCCs, as measured by colony-limiting dilution assays, was observed. To test if the conditions were damaging for the hematopoietic reconstituting cells, marrow cells collected from 5-FU-treated male donor mice were incubated with the cytosine deaminase adenoviral vector and then exposed to 5-FC either for 4 days in vitro before transplantation or for 14 days immediately after transplantation in vivo. There was no significant decrease in the reconstituting capability of the male marrow cells, as measured by their persistence in female irradiated recipients for up to 6 months after transplantation. These observations suggest that adenovirus-mediated gene transfer of the Escherichia coli cytosine deaminase gene followed by exposure to the nontoxic pro-drug 5-FC may be a potential strategy to selectively reduce the level of contaminating BCCs in collections of hematopoietic cells used for autografts in breast cancer patients.

Adenoviridae↗
PubMed1998

Neural circuit analysis of spatial working memory: role of pre- and parasubiculum, medial and lateral entorhinal cortex.

Using a continuous recognition memory procedure for spatial location information, rats were given sequential presentation of individual arms on a 12-arm maze. Each arm contained a Froot Loop reinforcement the first time it was presented, and latency to traverse the arm was measured. A subset of the arms were repeated, but did not contain reinforcement. Repeated arms were presented with lags ranging from zero to six (from zero to six different arm presentations occurred between the first and repeated presentation). After completion of acquisition training (significantly longer latencies for repeated arms in comparison with the first presentation of an arm), rats received lesions of the medial or lateral entorhinal cortex, pre- and parasubiculum, or served as sham-operated controls. Based on continued postsurgery training and additional tests, the results indicated that rats with pre- and parasubiculum or pre- and parasubiculum plus medial entorhinal cortex produced sustained impairment in performing the task. Medial or lateral entorhinal cortex and control lesions did not display any sustained deficits. The data suggest that working memory for spatial location information is mediated primarily by the pre- and parasubiculum, but not medial entorhinal and lateral entorhinal cortex.

Animals↗
PubMed1998

Chemotherapy immediately following autologous stem-cell transplantation in patients with advanced breast cancer.

Most patients relapse after high-dose chemotherapy (HDCT) with autologous stem-cell transplantation (ASCT) for metastatic breast cancer. Further chemotherapy immediately after hematopoietic recovery from ASCT is not given for fear of irreversibly damaging the newly engrafted stem cells. In a pilot chemoprotection trial, autologous CD34+ cells from patients with metastatic breast cancer were exposed to a replication-incompetent retroviral vector carrying MDR-1 cDNA and then reinfused after HDCT. Immediately on recovery, patients received multiple courses of escalating dose paclitaxel. All of the 10 patients tolerated reinfusion of modified cells without any toxicity and had myeloid engraftment within 12 days (range, 11-14). The bone marrow cells of three patients contained vector MDR-1-positive cells only at the time of the first course of posttransplant paclitaxel, indicating that the MDR-1 vector-modified cells had only short-term engrafting potential. A total of 83 courses of paclitaxel were administered starting at a median of 30 (range, 21-32) days from ASCT. The median dose of paclitaxel was 225 mg/m2 and the median interval between paclitaxel cycles of therapy was 21 (range, 20-41) days. Five of the six CR patients were able to receive all of the 12 courses of paclitaxel. Three patients who had achieved less than a complete response to the HDCT (2 patients) and partial response (1 patient) were converted to complete clinical responses during the 12 cycles of paclitaxel. No delayed toxicity or bone marrow failure was noted in these patients with a median follow-up of 2 years from ASCT. This is the first study of chemotherapy immediately after transplantation with autologous CD34+ cells. These data indicate that paclitaxel can be safely administered immediately after ASCT without any delayed toxicities. Paclitaxel given immediately after ASCT can further improve the response to pretransplant chemotherapy in patients with advanced breast cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

Growth and water relations of Eucalyptus marginata (jarrah) stands in response to thinning and fertilization.

We studied the effects of five thinning treatments (T1 = 5.5, T2 = 11, T3 = 16.5, T4 = 22.5 and T5 = 28.5 m(2) ha(-1) basal area under bark) x two fertilizer treatments (F0 = unfertilized and F1 = fertilized with 400 kg ha(-1) N plus 229 kg ha(-1) P) on growth and water relations of pole-sized Eucalyptus marginata J. Donn ex Sm. trees growing in southwestern Australia. Thinning reduced leaf area index (LAI) from 2.1 in the T4 and T5 treatments to 0.8 in the T1F0 treatment. Fertilizer had no effect on LAI in the T2, T4 or T5 treatments, but increased LAI by 45 and 20% in the T1 and T3 treatments, respectively. Thinning plus fertilizing increased diameter growth most in the fastest growing trees, from 0.4 cm year(-1) for trees in the T5F0 and T5F1 treatments to 0.7 and 1.2 cm year(-1) for trees in the T1F0 and T1F1 treatments, respectively. In both fertilizer treatments, stand basal area and volume growth increased with increasing stand density up to 15 m(2) ha(-1), and thereafter declined with increasing stand density, such that the growth rate of trees in the T5 treatment was only half of that at a stand density of 15 m(2) ha(-1). In response to fertilizer, growth rates of the slowest and fastest-growing trees increased from 0.35 and 3.5 m(2) ha(-1) year(-1) (F0) to 0.56 and 5.4 m(3) ha(-1) year(-1) (F1), respectively. Stand growth efficiency (growth per unit LAI) increased in response to thinning, and fertilizer increased stand growth efficiency at all stand densities. Throughout the dry season, T5 trees had lower predawn shoot water potentials (Psi(pd)) (minimum of -1.5 MPa) than T1 or T2 trees (minimum of -0.7 MPa). Fertilizer decreased Psi(pd) in T5 trees (by -0.9 and -1.5 MPa, respectively, in F0 and F1), but not in T1 or T2 trees. Stand growth rate was closely related to cumulative midday water stress (CMWS) over the dry season, and volume growth rate declined sharply from 6 m(3) ha(-1) year(-1) at a CMWS of 130 MPa days, to zero at a CMWS of 220 MPa days. Application of fertilizer to thinned stands increased LAI, stand growth efficiency and stand growth. In unthinned stands, fertilizer increased stand growth efficiency and stand growth; however, it also increased tree water stress, which limited the fertilizer-induced increases in LAI and growth. We attribute the increase in tree and stand growth in response to application of fertilizer to increased photosynthetic rates, increased allocation to stem wood, and in thinned stands also to higher LAIs.

Journal Article↗
PubMed1994

Right coronary artery with anomalous origin and slit ostium.

Right coronary arteries that arise from the left sinus or ectopically from the right sinus with a slit ostium can cause myocardial ischemia, myocardial infarction, or sudden death. The surgical repair of these anomalies has evolved toward a simpler operation that widens the orifice of origin and reduces the compression of the intramural segment. We have repaired these anomalies without mortality in 8 patients. We summarize our experience and the evolution of this procedure.

Adult↗
PubMed1990

Analysis of HLA-DQ genotypes and susceptibility in insulin-dependent diabetes mellitus.

There is evidence that certain alleles at the HLA-DQ locus are correlated with susceptibility to insulin-dependent diabetes mellitus (IDDM) and in particular that DQ beta-chain alleles containing aspartic acid at position 57 are protective. The availability of a large group of patients with IDDM enabled us to assess the role of HLA-DQ alleles in susceptibility to the disease in order to confirm and extend recent observations derived from studies of smaller numbers of patients. Using allele-specific oligonucleotide probes and the polymerase chain reaction, we studied 266 unrelated patients with IDDM and 203 unrelated normal subjects for eight HLA-DQ beta-chain alleles. Two major findings emerged from these studies. First, the presence of an HLA-DQw1.2 allele was protective. Only 6 of the 266 patients with IDDM (2.3 percent) were positive for HLA-DQw1.2, as compared with 74 of the 203 normal subjects (36.4 percent; P less than 0.001). Thus, persons with the HLA-DQw1.2 allele, which is one of the polymorphic forms of the beta chain of the HLA-DQ molecule, rarely had IDDM, no matter which other HLA-DQ beta-chain allele they inherited ("dominant protection"). Second, the presence of the HLA-DQw8 allele increased the risk of IDDM. The relative risk of IDDM was 5.6 in persons homozygous for HLA-DQw8, and it was similar in persons with the HLA-DQw1.1/DQw8 or HLA-DQw2/DQw8 haplotype ("dominant susceptibility"). However, the relative risk of IDDM in persons who had the HLA-DQw1.2/DQw8 haplotype was 0.37, demonstrating that the protective effect of HLA-DQw1.2 predominated over the effect of HLA-DQw8. We conclude that the presence of the HLA Class II antigen DQw1.2 is strongly protective against the development of IDDM, and that complete HLA-DQ typing is necessary for accurate assessment of susceptibility to IDDM.

Adult↗
PubMed1989

Ehrlichiosis.

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Animals↗
PubMed1985

Potency and efficacy of inactivated bluetongue virus vaccines.

Bluetongue virus (BTV) was chemically inactivated and was shown to elicit neutralizing antibodies in vaccinated rabbits and sheep. In sheep, the neutralizing antibody was shown to be protective by immunity challenge with virulent virus. These studies have shown the feasibility of safe and effective inactivated vaccines for bluetongue (BT) disease of sheep.

Animals↗
PubMed1985

[Cerestore].

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Aluminum Oxide↗
PubMed1982

Radionuclide ejection fraction: comparison of response to treadmill and bicycle exercise.

Most exercise radionuclide studies utilise the supine bicycle ergometer during imaging, although exercise on a treadmill results in greater cardiovascular stress. Twenty-three patients were studied to compare the radionuclide left ventricular ejection fraction (LVEF) estimated immediately following treadmill exercise with that obtained at peak supine bicycle exercise in patients with coronary artery disease (CAD) and patients with normal coronary arteries. In 14 patients with CAD the rest LVEF was 47 +/- 7% (mean +/- SD) by first pass and 49 +/- 10% by equilibrium blood pool techniques. Immediately following maximum treadmill exercise, 13 of the 14 patients with coronary artery disease showed either no change or a decrease in LVEF, the LVEF was 49 +/- 7% (P = NS) and 47 +/- 8% (P = NS) by first pass and equilibrium determinations respectively. In comparison the LVEF during peak supine bicycle exercise decreased significantly to 42 +/- 12% (P less than 0.01). In nine patients with angiographically normal coronary arteries the rest LVEF was 51 +/- 4% by first pass and 54 +/- 6% by equilibrium, increasing to 67 +/- 7% (P less than 0.01) and 64 +/- 7% (P less than 0.01) respectively following treadmill exercise. During peak bicycle exercise LVEF increased in the normal patients to 61 +/- 7% (P less than 0.05). These data suggest that quantitative radionuclide angiography following either maximum treadmill exercise or during peak bicycle exercise can discriminate between patients with coronary artery disease and normal subjects, although the magnitude of left ventricular functional changes are greater during bicycle stress.

Adult↗