PubMed Health⌕ Search

Biomedical subjects

J O'Dea

Publications and source records attributed to J O'Dea.

17 recordsLinked to original sources

Uptake of radionuclides by vegetation at a High Arctic location.

Radionuclide levels in vegetation from a High Arctic location were studied and compared to in situ soil concentrations. Levels of the anthropogenic radionuclide 137Cs and the natural radionuclides 40K, 238U, 226Ra and 232Th are discussed and transfer factor (TF) values and aggregated transfer (Tag) values are calculated for vascular plants. Levels of 137Cs in vegetation generally followed the order mosses > lichen > vascular plants. The uptake of 137Cs in vascular plants showed an inverse relationship with the uptake of 40K, with 137Cs TF and Tag values generally higher than 40K TF and Tag values. 40K activity concentrations in all vegetation showed little correlation to associated soil concentrations, while the uptake of 238U, 226Ra and 232Th by vascular and non-vascular plants was generally low.

Air Pollutants, Radioactive↗

Variation in intubation decisions for patients with chronic obstructive pulmonary disease in one critical care network.

BACKGROUND: Anecdotal evidence suggests variation in intubation decisions for chronic obstructive pulmonary disease (COPD) patients with respiratory failure, but little is known about the extent of or reasons for this variability. AIM: To describe clinician decision-making for patients with exacerbations of COPD considered for intubation. DESIGN: Telephone simulation study. METHODS: Consultants responsible for COPD admissions in the Heart of England Critical Care network were asked to decide whether or not to admit three patients with COPD to ICU on the basis of information conveyed over the telephone. Consultants were also asked to predict patients survival in ICU hospital and at 180 days on the assumption that the patient did receive ICU care. RESULTS: Of the 120 consultants, 98 (82%) took part; 89% would admit patient 1, 64% patient 2, and 40% patient 3. The prediction of survival if ICU admission had occurred differed significantly between admitters and non-admitters. Mean predicted post-ICU hospital survival for patient 1 was 46% (95%CI 43-49) for admitters, and 13% (95%CI 6-19) for non-admitters (p < 0.001). The respective figures for patient 2 were 38% (95%CI 34-42) vs. 12% (95%CI 8-15) (p < 0.001), and for patient 3, 28% (95%CI 24-33) vs. 13% (95%CI 10-16) (p < 0.001). For a housebound COPD patient in their mid 70s, the mean (SD) threshold of predicted hospital survival below which consultants would recommend not admitting to ICU was 22% (13.2%). CONCLUSIONS: Consultants differed markedly in their admitting decisions about identical patients. Objective outcome prediction models might improve equity in ICU bed use for patients with COPD.

Aged↗

Generation of retroviral packaging and producer cell lines for large-scale vector production and clinical application: improved safety and high titer.

For many applications, human clinical therapies using retroviral vectors still require many technological improvements in key areas of vector design and production. These improvements include higher unprocessed manufacturing titers, complement-resistant vectors, and minimized potential to generate replication-competent retrovirus (RCR). To address these issues, we have developed a panel of human packaging cell lines (PCLs) with reduced homology between retroviral vector and packaging components. These reduced-homology PCLs allowed for the use of a novel high multiplicity of transduction ("high m.o. t.") method to introduce multiple copies of provector within vector-producing cell lines (VPCLs), resulting in high-titer vector without the generation of RCR. In a distinct approach to increase vector yields, we integrated manufacturing parameters into screening strategies and clone selection for large-scale vector production. Collectively, these improvements have resulted in the development of diverse VPCLs with unprocessed titers exceeding 2 x 10(7) CFU/ml. Using this technology, human Factor VIII VPCLs yielding titers as high as 2 x 10(8) CFU/ml unprocessed supernatant were generated. These cell lines produce complement-resistant vector particles (N. J. DePolo et al., J. Virol. 73: 6708-6714, 1999) and provide the basis for an ongoing Factor VIII gene therapy clinical trial.

Base Sequence↗

Preventing eating and body image problems in children and adolescents using the Health Promoting Schools Framework.

This paper outlines the Health Promoting Schools Framework and how it may be implemented in schools for preventing eating and body image problems. Discussion focuses on the efficacy of preventive school-based strategies, and on the safest and most successful interventions. The Framework encompasses three major areas of intervention in the school and community: 1) School curriculum, teaching, and learning; 2) School ethos, environment, and organization; and 3) School-community partnerships and services. Suggested strategies for implementing the Framework are outlined. A case study of how a girls high school adapted the new approach for dealing with the problem of eating and body image problems is presented.

Adolescent↗

Genetic immunization of chimpanzees chronically infected with the hepatitis B virus, using a recombinant retroviral vector encoding the hepatitis B virus core antigen.

Cytotoxic T lymphocyte (CTL) activity and CD4+ helper T cell responses to the hepatitis B virus (HBV) core antigen (HBcAg) have been implicated in clearance of acute and chronic HBV infections. We showed that intramuscular injections of a novel recombinant retroviral vector expressing an HBcAg-neomycin phosphotransferase II (HBc-NEO) fusion protein induces HBc/eAg-specific antibodies and CD4+ and CD8+ T cell responses in mice and rhesus monkeys. We have now immunized three chronically infected chimpanzees, each with 10(10) CFU of nonreplicating retroviral vector particles expressing the HBc-NEO fusion protein. Of two immunized chimpanzees examined for CTL responses, one developed HBcAg-specific CTLs and showed marginal, transient elevations of alanine aminotransferase (ALT) levels following injection. However, both chimpanzees remained positive for serum HBeAg, negative for anti-HBe antibody by conventional assays, and displayed no change in HBV viral load throughout the study. In contrast, the third chimpanzee exhibited a traditional seroconversion evidenced by a loss of serum HBeAg and the subsequent emergence of anti-HBe antibodies within 24 weeks after the first injection. Simultaneously, two transient ALT flares and a significant decrease in the serum HBV DNA levels were noted. Despite its limitations, the present study demonstrates (1) the safety of treatment with high titers of retroviral vector in chimpanzees, (2) the capability of a retroviral vector expressing HBcAg to stimulate immune responses in HBV chronic carrier chimpanzees, and (3) that retroviral vector immunization may be therapeutically beneficial in the treatment of chronic HBV infection.

Amino Acid Sequence↗

Coronary artery bypass graft surgery in Newfoundland and Labrador.

BACKGROUND: Newfoundland and Labrador, like other health care jurisdictions, is faced with widening gaps between the demands for health care and a strained ability to supply the necessary resources. The authors carried out a study to determine the rates of appropriate and inappropriate coronary artery bypass grafting (CABG) in the province and the waiting times for this surgery. METHODS: This retrospective cohort study was performed in the tertiary care hospital that receives all referrals for coronary angiography and coronary artery revascularization for Newfoundland and Labrador. By reviewing the hospital records, the authors identified 2 groups of patients: those in whom critical coronary artery disease was diagnosed on the basis of coronary angiography and who were referred for CABG between Apr. 1, 1994, and Mar. 31, 1995, and those who actually underwent the procedure during that period. By applying specific criteria developed by the RAND Corporation, the authors determined the appropriateness and necessity of CABG in each case. They also compared waiting times for CABG with optimal waiting times; as determined by a consensus-based priority score. RESULTS: A total of 338 patients underwent CABG during the study period. The cases were characterized by multivessel disease and late-stage angina symptoms. Almost all of the patients had high appropriateness scores (7-9), and nearly 95% had high necessity scores (7-9). However, during the study period, the waiting list increased by about 20%, because a total of 391 patients were referred by the weekly cardiovascular surgery conference; the authors identified these and an additional 31 patients as having necessity scores of 7 or more. Only 7 (23%) of 31 patients for whom CABG was considered very urgent underwent surgery within the recommended 24 hours, and only 30 (24%) of the 122 patients for whom CABG was considered urgent underwent surgery within the recommended 72 hours. INTERPRETATION: These results provide evidence that the cardiac surgery program in Newfoundland and Labrador is performing CABG in patients for whom surgical revascularization is highly appropriate and necessary. Access to CABG is less than ideal, however, since the waiting list continues to expand, and many patients wait beyond the recommended time for surgery.

Cohort Studies↗

Characterization of CD8+ cytotoxic T-lymphocyte responses after genetic immunization with retrovirus vectors expressing different forms of the hepatitis B virus core and e antigens.

Cytotoxic T-lymphocyte (CTL) activity appears to play an important role in resolving hepatitis B virus (HBV) infection, and the ability to induce such responses remains an important goal for developing effective immunotherapeutics. A panel of recombinant retrovirus vectors expressing different forms of the HBV core antigen (HBcAg) or e antigen (eAg) were found to induce antigen-specific major histocompatibility complex-restricted CTL responses in both mice and macaques. In addition, a novel retrovirus vector expressing an HBcAg-neomycin phosphotransferase II (HBc-Neo) fusion protein [LHBc-NEO(6A3)], which allows the measurement of the anti-Neo antibody response as a means of directly tracking biological activity of the vector, was generated. Doses greater than 10(7) CFU were necessary to induce CTL responses in H-2(k) mice. Intramuscular injections with 10(8) CFU of the LHBc-NEO(6A3) retrovirus vector into rhesus monkeys induced HBc/eAg-specific antibody production and CD8+ CTLs. The CTL response from one of the two responder rhesus monkeys was directed against a 9-residue peptide, GELMTLATW, at positions 63 to 71 of the HBc/eAg sequence. The CTL response is long lived, being detectable as late as 16 weeks after immunization, and can be boosted upon reimmunization. The potent ability of recombinant retrovirus vectors to induce HBcAg- and eAg-specific CTL responses may prove beneficial as a therapeutic treatment for chronic hepatitis B infection.

Animals↗

Characterization of humoral and CD4+ cellular responses after genetic immunization with retroviral vectors expressing different forms of the hepatitis B virus core and e antigens.

The humoral and CD4+ cellular immune responses in mice following genetic immunization with three retroviral vectors encoding different forms of hepatitis B virus core antigen (HBcAg) and e antigen (HBeAg) were analyzed. The retroviral vectors induced expression of intracellular HBcAg (HBc[3A4]), secreted HBeAg (HBe[5A2]), or an intracellular HBcAg-neomycin phosphoryltransferase fusion protein (HBc-NEO[6A3]). Specific antibody levels and immunoglobulin G isotype restriction were highly dependent on both the host major histocompatibility complex and the transferred gene. Humoral and CD4+ cellular HBcAg and/or HBeAg (HBc/eAg)-specific immune responses following retroviral vector immunization were of a lower magnitude but followed the same characteristics compared with those after immunization with HBc/eAg in adjuvant. Two factors influenced the humoral responses. First, in vivo depletion of CD8+ cells in HBc-NEO[6A3]-immunized H-2k mice abrogated both HBcAg-specific antibodies and in vitro-detectable cytotoxic T lymphocytes. Second, priming of H-2b mice with an HBc/eAg-derived T-helper (Th) peptide in adjuvant prior to retroviral vector immunization greatly enhanced the HBc/eAg-specific humoral responses to all three vectors, suggesting that insufficient HBc/eAg-specific CD4+ Th-cell priming limits the humoral responses. In conclusion, direct injection of retroviral vectors seems to be effective in priming HBc/eAg-specific CD8+ but comparatively inefficient in priming CD4+ Th cells and subsequently specific antibodies. However, the limited HBc/eAg-specific CD4+ cell priming can effectively be circumvented by prior administration of a recombinant or synthetic form of HBc/eAg in adjuvant.

Animals↗

Erythrocyte membrane stearic and oleic acid ratios in breast cancer.

A case control study has been conducted to determine the value of stearic/oleic acid ratios in the erythrocyte membranes of women at the time of presentation with breast cancer. No difference was found between the stearic/oleic acid ratio of cases and that of controls with benign breast condition or normal volunteers. Furthermore, within clinical stages of breast cancer, no differences were detected. This ratio does not appear to be of value as a marker of malignancy, or of tumour burden.

Breast Neoplasms↗

Proteinuria and renal function in diabetic patients fed a diet moderately restricted in protein.

Protein restriction has been used in the treatment of renal disease and may also be beneficial in the management of diabetic nephropathy. We evaluated the effects of moderate protein restriction (0.6 g/kg ideal body weight per day) for a 3-mo period on renal function in seven diabetic patients. Moderate protein restriction led to a decrease of approximately 50% in the albumin excretion rate in patients with overt proteinuria or microalbuminuria. This decrease occurred in some patients without a decrease in glomerular filtration rate, renal plasma flow, or plasma albumin concentration and may reflect subtle changes in filtration properties or permeability of glomeruli. In this pilot study moderate protein restriction has marked effects on albumin excretion irrespective of the initial degree of renal impairment. It is therefore suitable for longer-term study of its effects on the progression of renal disease in both patients with overt and incipient diabetic nephropathy.

Adult↗

Cromolyn sodium in seasonal allergic conjunctivitis.

A formulation of 2% cromolyn sodium (CS) ophthalmic solution without the preservative, 2-phenylethanol, was compared with placebo in 58 patients with seasonal allergic conjunctivitis. Selection was based on history and positive skin tests. Neither immunotherapy nor use of antihistamines was allowed. This study was double-blinded and stratified by RAST scores to assure comparable groups. Either CS or placebo was used six times daily. Patients were observed weekly for 5 weeks during the peak of the fall weed-pollen exposure. Nasal symptoms were treated as required with beclomethasone nasal spray, and uncontrolled ocular symptoms were treated with boric acid and ephedrine solution. Nasal and ocular symptoms were recorded. There was a significant suppression of eye symptoms in the group receiving CS ophthalmic solution (p less than 0.02) during weeks 2, 4, and 5. There was a trend for nasal symptoms and the requirement for nasal beclomethasone to be less in patients receiving CS.

Adolescent↗