Biomedical subjects

Alan Edwards

Publications and source records attributed to Alan Edwards.

7 recordsLinked to original sources

PubMed2006

Presenting statistical uncertainty on cytogenetic dose estimates.

Cytogenetic dosimetry results are customarily accompanied by 95% confidence limits and the derivation of these limits is discussed. Simply presenting values of the best estimate of dose and 95% limits assumes that recipients of dosimetry reports, possibly the patients themselves, have a sufficient grasp of statistics to comprehend the concept of uncertainty. Two further methods have been developed to aid improved understanding for the lay person. The first method, particularly useful for suspected low doses, presents a simple odds ratio indicating that the results favour either zero dose or that suspected; for example, from an unexpected dose recorded on a badge. The second method, described fully here for the first time, uses a graphical illustration of a normalised distribution of dose so that one may visualise the area beneath a curve that represents the probability that the dose lies within various bounds.

Cytogenetic Analysis↗

PubMed2003

Adenoma multiplicity in irradiated Apc(Min) mice is modified by chromosome 16 segments from BALB/c.

Ionizing radiation (IR) is a well-characterized carcinogen in humans and mice. The BALB/c mouse strain is unusually sensitive to IR-induced tissue damage and cancer development in a range of organs, suggestive of a partial defect in DNA damage response. This has been confirmed by finding BALB/c-specific functional polymorphism in Prkdc, a gene on mouse chromosome 16 that encodes the catalytic subunit of DNA-dependent protein kinase. Prkdc(BALB) has been associated with increased susceptibility to IR-induced mammary and lymphatic neoplasia. Here, we provide evidence that chromosome 16 segments from BALB/c interact with Apc(Min) (multiple intestinal neoplasia) and specifically enhance IR-induced adenoma development in the upper part of the small intestine.

Adenoma↗

PubMed2003

In vivo biostability of a poly(carbonate-urea)urethane graft.

In peripheral and coronary bypass surgery, the patency of prosthetic grafts is inferior to autologous vein, mainly due to intimal hyperplasia caused in part by compliance mismatch between rigid graft and elastic host artery. We have developed a compliant poly(carbonate-urea)urethane vascular graft "MyoLink" which was biostable in vitro degradation studies. To further investigate the biostability of this material, we report a long-term in vivo study on 8 beagle dogs (15+/-3 kg) implanted with this graft (ID 5mm) in the aorta-iliac position; three grafts were harvested at 18 months to assess short-term biodegradation, with one animal having died from an unrelated infection. The 4 remaining grafts were harvested at 36 months for analysis by: (1) histology, (2) compliance measurements and (3) environmental scanning electron microscopy (ESEM); gel permeation chromatography (GPC); attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) and radial tensile strength analysis. There was no infection or inflammation of the grafts or surrounding tissues. Histological analysis showed a well-developed neointima but only at the distal anastomosis. There were no significant differences in compliance pre- and post-implantation and no evidence of material curvature, radial expansion or chemical breakdown, ESEM and GPC showed no signs of degradation. Peak height analysis with ATR-FTIR of the 1740 cm(-1) (C=O of carbonate) and 1253 cm(-1) bands (C-O-C of CO-O-C) showed a loss of carbonate carbonyl but was not statistically significant. Radial tensile strength remained within batch release specifications.This polyurethane graft retains its compliance post-implantation, whilst exhibiting only a minor hydrolysis of the amorphous segment, confirming its biostability in vivo up to 3 years.

Anastomosis, Surgical↗

PubMed2002

Functional evidence from microcell-mediated chromosome transfer of myeloid leukemia suppressor genes on human chromosomes 7 and 11.

The long arm of human chromosome 7 between 7q22 and 7q36 has been identified as a region harboring one or more tumor-suppressor genes (TSGs) inactivated in acute myeloid leukemia (AML). Additional TSGs mapping to other chromosomes may well be involved in the etiology of this disease. For example, experiments using a mouse model system have indicated the possible presence of an AML TSG at 11p11-12. Microcell-mediated chromosome transfer (MMCT) has been used to introduce human chromosomes 7 and 11 into a murine myeloid leukemia cell line. A proportion of MMCT hybrid clones containing either whole chromosome 7 or fragments of chromosome 11 showed a significant delay in leukemogenic onset when injected into syngeneic mice. Screening of hybrid clones did not associate any human microsatellite markers with decreased leukemogenic potential in vivo. However, preliminary evidence was obtained of allelic loss at chromosomal regions homologous with human 7q22 in murine F1 hybrid AMLs. Our data provide functional evidence of AML-associated TSGs localized to human chromosomes 7 and 11 in support of previously published studies on cytogenetic and allelic losses associated with AML development.

Acute Disease↗

PubMed2002

In vitro stability of a novel compliant poly(carbonate-urea)urethane to oxidative and hydrolytic stress.

Poly(ester)urethane and poly(ether)urethane vascular grafts fail in vivo because of hydrolytic and oxidative degradative mechanisms. Studies have shown that poly(carbonate)urethanes have enhanced resistance. There is still a need for a viable, nonrigid, small-diameter, synthetic vascular graft. In this study, we sought to confirm this by exposing a novel formulation of compliant poly(carbonate-urea)urethane (CPU) manufactured by an innovative process, resulting in a stress-free. Small-diameter prosthesis, and a conventional poly(ether)urethane Pulse-Tec graft known to readily undergo oxidation in a variety of degradative solutions, and we assessed them for the development of oxidative and hydrolytic degradation, changes in elastic properties, and chemical stability. To simulate the in vivo environment, we used buffered solutions of phospholipase A(2) and cholesterol esterase; solutions of H(2)O(2)/CoCl(2), t-butyl peroxide/CoCl(2) (t-but/CoCl(2)), and glutathione/t-butyl peroxide/CoCl(2) (Glut/t-but/CoCl(2)); and plasma fractions I-IV, which were derived from fresh human plasma centrifuged in poly(ethylene glycol). To act as a negative control, both graft types were incubated in distilled water. Samples of both graft types (100 mm with a 5.0-mm inner diameter) were incubated in these solutions at 37 degrees C for 70 days before environmental scanning electron microscopy, radial tensile strength and quality control, gel permeation chromatography, and in vitro compliance assessments were performed. Oxidative degradation was ascertained from significant changes in molecular weight with respect to a control on all Pulse-Tec grafts treated with t-but/CoCl(2), Glut/t-but/CoCl(2), and plasma fractions I-III. Pulse-Tec grafts exposed to the H(2)O(2)/CoCl(2) mixture had significantly greater compliance than controls incubated in distilled water (p < 0.001 at 50 mmHg). No changes in molecular weight with respect to the control were observed for the CPU samples; only those immersed in t-but/CoCl(2) and Glut/t-but/CoCl(2) showed an 11% increase in molecular weight to 108,000. Only CPU grafts treated with the Glut/t-but/CoCl(2) mixture exhibited significantly greater compliance (p < 0.05 at 50 mmHg). Overall, results from this study indicate that CPU presents a far greater chemical stability than poly(ether)-urethane grafts do.

Biocompatible Materials↗

PubMed2002

A major breakpoint cluster domain in murine radiation-induced acute myeloid leukemia.

Cytogenetic and molecular studies have provided evidence of the clustering of chromosome 2 deletion breakpoints in radiation-induced murine acute myeloid leukemia (AML). Moreover, clustering occurs in at least two fragile domains rich in telomere-like arrays. Here we describe a physical map of the distal breakpoint cluster and confirm the presence of inverted head-to-head telomeric sequence arrays. These potentially recombinogenic sequences were not, however, the direct focus for post-irradiation chromosome breakage in AML. Instead, the two arrays bordered a 2.5-kb sequence with properties expected of a nuclear matrix attachment region (MAR). The putative MAR co-localized in the fragile domain with genes important to the hemopoietic system (leukocyte tyrosine kinase, zinc finger protein 106, erythrocyte protein band 4.2, and beta(2)-microglobulin (beta2m)); the beta2m subdomain was a particular focus of breakage. On the basis of these and other data, we suggest that AML-associated chromosome 2 fragility in the mouse is a consequence of domain-specific fragility in genomic domains containing numerous genes critical to the hemopoietic system. Recorded with the permission of the controller of Her Majesty's Stationery Office. Published by Wiley-Liss, Inc.

Acute Disease↗

PubMed2002

The combination of nebulized sodium cromoglycate and salbutamol in the treatment of moderate-to-severe asthma in children.

The aim of this multi-centre prospective study was to evaluate the efficacy, tolerability, and safety of the combination of sodium cromoglycate (SCG) and salbutamol (administered as a nebulized solution), compared to SCG alone and salbutamol alone, in the management of severe, intractable asthma in childhood. The study was an open, randomized, cross-over trial of 12 weeks' duration in children with moderate-to-severe intractable asthma. All treatments were administered twice daily by powered nebulizer. The primary outcome measure was the change in asthma severity, as measured by the mean asthma score during the last 2 weeks of a baseline period and the last 2 weeks of each treatment. Secondary outcome measure was the patient's opinion of the effectiveness of treatment. The change in asthma scores from baseline values were significantly greater with the combination treatment compared to each component administered separately. The mean difference in asthma score between the combination and salbutamol was: -7.5; 95% CI, -11.70 to -3.29 (p < 0.0001). The mean difference between the combination and SCG was: -8.53; 95% CI, -14.03 to -3.25 (p < 0.0001). Patients were also significantly in favor of combination treatment (p < 0.001 vs. salbutamol; p < 0.01 vs. SCG). Two patients reported adverse effects. We concluded that regular twice-daily inhalation of a combination of SCG and salbutamol gave better control of symptoms than previous treatments in patients with severe, intractable asthma. Few adverse effects with this therapy suggest that it is extremely useful, safe, and effective.

Albuterol↗