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Biomedical subjects

J Donnelly

Publications and source records attributed to J Donnelly.

At least 19 recordsLinked to original sources

Synergistic adjuvant activity of immunostimulatory DNA and oil/water emulsions for immunization with HIV p55 gag antigen.

A synthetic oligonucleotide containing a previously identified adjuvant active CpG DNA sequence was evaluated for its ability to augment antibody and CTL responses to p55 gag from HIV-1 in mice. Surprisingly, the CpG oligonucleotide, although, it had previously been described as the most potent adjuvant sequence in mice for the particulate HbsAg, was ineffective when used in a simple combination with urea-solubilized p55 antigen. However, a potent adjuvant effect was observed with the CpG sequence when it was formulated with emulsions. Enhancement of antibody titer by CpG emulsion formulations was observed with urea-solubilized p55 antigen, however, significantly higher titers were obtained with p55 bound to polylactide-co-glycolide microparticles. In both cases IgG2a was enhanced in the presence of CpG. It appears likely that presentation of CpG with emulsions and particulate antigens enhances their delivery into antigen presenting cells (APC) and results in more effective presentation of antigen and adjuvant. To support this hypothesis, preliminary in vitro studies were undertaken to show upregulation of CD86 on mouse bone marrow-derived dendritic cells (BMDC) in vitro, following incubation with CpG formulations.

AIDS Vaccines↗

Quantification of mitral regurgitation orifice area by 3-dimensional echocardiography: comparison with effective regurgitant orifice area by PISA method and proximal regurgitant jet diameter.

BACKGROUND: The evaluation of mitral regurgitation (MR) by 3-dimensional (3D) echo has generally been performed by reconstruction of Doppler regurgitant jets but there are little data on measuring anatomic regurgitant orifice area (AROA) directly from 3D mitral valve (MV) reconstructions. METHODS AND RESULTS: Transoesophageal echo (TOE) 3D images were acquired from 38 unselected patients (age 59+/-11 years, ten in atrial fibrillation) with various degrees of MR. In all patients MV was reconstructed en face from the left atrium (LA) and the left ventricle (LV). AROA was measured by planimetry from 3D pictures and compared to the effective regurgitant orifice area (EROA) by proximal isovelocity surface area and proximal MR jet width from 2D echo. AROA was measured in 95% of patients from LA, 89% from LV and in 84% from both LA and LV. Good correlation was found between EROA and AROA measured from both LA (r=0.97, P<0.0001) and LV (r=0.87, P<0.0001). The mean difference between LA-AROA and EROA was -3.01+/-6.12 mm(2) and -7.18+/-13.84 mm(2) for LV-AROA (P<0.01, respectively). An acceptable correlation was found between the proximal MR jet width and AROA from LA (r=0.71, P<0.0001) and LV perspective (r=0.68, P<0.0001). AROA>or=25 mm(2) differentiated mild MR (graded 1-2) from moderately severe (graded 3-4) with 80-90% accuracy. CONCLUSIONS: 3D TOE provides important quantitative information on both the mechanism and the severity of MR in an unselected group of patients. AROA enables quantification of MR with excellent agreement with the accepted clinical method of proximal flow convergence.

Adult↗

Vacuum assisted closure system in the management of enterocutaneous fistulae.

BACKGROUND: A very important yet often troublesome element in the conservative management of enterocutaneous fistulae is the protection of the surrounding skin from contact with the effluent. This report describes the successful use of a vacuum assisted closure (VAC) system in dealing with this problem. METHODS: The results of using the VAC system were studied in three patients with moderate or high volume output enterocutaneous fistulae where conventional treatment had failed to prevent skin excoriation. RESULTS: The VAC system was found to be highly effective in controlling fistula effluent and in promoting healing of excoriated skin in all three patients. Complete healing of the fistula was also achieved in two of the three patients. CONCLUSION: The VAC system can be an effective and economically viable method of containing fistula effluent and protecting the skin of patients with enterocutaneous fistulae. Contrary to conventional thought, the VAC system may also actually promote healing of the fistula.

Adult↗

The cosmic ray actinide charge spectrum derived from a 10 m2 array of solid state nuclear track detectors in Earth orbit.

The DIAS-ESTEC Ultra Heavy Cosmic Ray Experiment (UHCRE) on the Long Duration Exposure Facility, collected approximately 3000 cosmic ray nuclei with Z > 65 in the energy region E > 1.5 GeV nucleon-1 during a six year exposure in Earth orbit. The entire accessible collecting area of the solid state nuclear track detector (SSNTD) array has been scanned for actinides, yielding a sample of 30 from an exposure of approximately 150 m2 sr yr. The UHCRE experimental setup is described and the observed charge spectrum presented. The current best value for the cosmic ray actinide relative abundance, (Z > 88)/(74 < or = Z < or = 87), is reported.

Actinoid Series Elements↗

An HIV/AIDS risk-reduction program for mentally ill hospital patients: assessing readiness for change.

This study evaluated the effectiveness of an HIV/AIDS cognitive-behavioral skills-training program in promoting readiness for behavior change among a sample of psychiatric inpatients. Significant differences were found in the domain of precontemplation for women patients, in domain of contemplation for patients diagnosed with a psychotic disorder, and in the domain of action for men and for patients with a mood disorder. In all areas, difference scores reflected an improvement between pre- and posttest levels.

Acquired Immunodeficiency Syndrome↗

Importance of complement source in measuring meningococcal bactericidal titers.

Complement-mediated bactericidal antibodies in serum confer protection against meningococcal disease. The minimum protective titer is estimated to be between 1:4 and 1:8 when measured by the Goldschneider assay performed with human complement, the assay used in the 1960s to establish the correlation between bactericidal antibodies and protection. A more recently described bactericidal assay standardized by an international consortium uses rabbit complement, which is known to augment bactericidal titers. To define a protective titer measured by the standardized assay, we compared bactericidal titers against serogroup C strains measured by this assay to titers measured by the assay described by Goldschneider et al. A titer of > or =1:128 measured by the standardized assay was needed to predict with > or =80% certainty a positive titer of > or =1:4 as measured by the Goldschneider assay. However, the majority of samples with titers of 1:4 measured by the Goldschneider assay had titers of <1:128 when measured by the standardized assay. Therefore, by the results of the standardized assay such persons would be falsely categorized as being susceptible to disease. In conclusion, high bactericidal titers measured with the standardized assay performed with rabbit complement are predictive of protection, but no threshold titer is both sensitive and specific for predicting a positive titer measured by the Goldschneider assay using human complement. Up to 10% of the U.S. adult population lacks intrinsic bactericidal activity against serogroup C strains in serum and can serve as complement donors. Therefore, use of the Goldschneider assay or an equivalent assay performed with human complement is preferred over assays that use rabbit complement.

Adult↗

An analysis of consultations with the crowd doctors at Glasgow Celtic football club, season 1999-2000.

OBJECTIVE: To analyse all clinical presentations to the crowd doctors at Scotland's largest football stadium over the course of one complete season. METHODS: A standard clinical record form was used to document all consultations with the crowd doctors including treatment and subsequent referrals. The relevance of alcohol consumption was assessed. RESULTS: A total of 127 casualties were seen at 26 matches, a mean of 4.88 per match. Twenty casualties were transferred to hospital, including one successfully defibrillated after a cardiac arrest. Alcohol excess was a major contributing factor in 26 cases. CONCLUSIONS: The workload of the crowd doctors was very variable and diverse. The social problem of excessive alcohol consumption contributed considerably to the workload. The provision of medical facilities at football grounds means that attendance there is now one of the least adverse circumstances in which to have a cardiac arrest. The study confirmed previous impressions that more casualties are seen at high profile matches.

Adolescent↗

Assessing sexuality attitudes and behaviors and correlates of alcohol and drugs.

The association between sexual abstinence and use of alcohol, cigarettes, and marijuana was examined in data from questionnaires completed by 874 students in Grades 6 through 8 at six urban schools. These students participated in a program that implemented and evaluated an educational program on abstinence sexuality. It focused on raising self-esteem, improving communication skills, and learning to set life goals. The evaluation instrument contained items assessing sexuality and attitudes toward behaviors related to drug use. Use of each drug (alcohol, tobacco, and marijuana) was significantly (p < .00001) and positively associated with self-report of having experienced sexual intercourse and expectation of having intercourse during the next year.

Adolescent↗

Follow-up of breast cancer: time for a new approach?

After treatment for breast cancer women are monitored for recurrent disease by means of routine hospital-based follow-up appointments. The aim of this study is to determine the efficiency of this system, by establishing how recurrence presents to our hospital. The study comes at a time of increasing pressure on breast clinics from new patient referrals and the need, since April 1999, to see all cases classified as urgent within two weeks of referral. A consecutive series of 643 patients who presented with operable breast cancer between 1992 and 1998 were reviewed. Details about the 108 patients who had locoregional or metastatic relapse were obtained from our breast cancer database and their clinical records. Full data were available on 104 patients: 77 (74%) were seen at expedited (interval) appointments and a further 18 (17.3%) drew attention to symptoms at a routine visit. Two cases of locoregional recurrence were revealed by surveillance imaging. Unsuspected disease, locoregional in all cases, was detected on examination in 7 (6.7%) patients. The median time to presentation of recurrence was 19 months for metastatic and 18 months for locoregional disease. Breast cancer recurrence usually presents to an interval clinic. Most cases that are confirmed following a routine review are already symptomatic. Long-term routine hospital follow-up after treatment for breast cancer appears inefficient and unnecessary. Following liaison with local general practitioners we propose to discharge patients from routine review after two years. Thereafter they will have scheduled appointments with their GPs with immediate access to specialist review in the breast care unit if required.

Breast Neoplasms↗

Potency of a genetically detoxified mucosal adjuvant derived from the heat-labile enterotoxin of Escherichia coli (LTK63) is not adversely affected by the presence of preexisting immunity to the adjuvant.

The objective of the current studies was to evaluate whether the potency of a genetically detoxified mucosal adjuvant, derived from heat-labile enterotoxin of Escherichia coli (LTK63), was adversely affected by preexisting immunity. Studies of mice and pigs have involved consecutive intranasal immunization with LTK63 and 2 different vaccines (influenza virus hemagglutinin and a protein-polysaccharide conjugate of Neisseria meningitidis group C). The antibody responses to the vaccines plus LTK63 in naive animals were compared with the responses achieved in animals that previously had been immunized with the alternate vaccine plus LTK63. The data showed that the responses of both animal models to intranasal immunization were not adversely affected by the presence of preexisting immunity to the LTK63 adjuvant.

Adjuvants, Immunologic↗

Developing a multidisciplinary complex wound care service.

This article will describe the development of a dedicated multidisciplinary complex/chronic wound care service. Using a recognized framework, the article will demonstrate how the needs of patients were first assessed and then addressed. The article will conclude that although more research is required, the results of this audit suggest that patients with long-standing complex/chronic wounds benefit from the care of a dedicated multidisciplinary wound care team. For the purpose of this article the term 'complex' is defined as any wound which is not progressing as expected despite the application of good quality standard wound care.

Chronic Disease↗

NCCN Practice Guidelines for Cancer-Related Fatigue.

These guidelines propose a treatment algorithm in which patients are evaluated regularly for fatigue, using a brief screening instrument, and are treated as indicated by their fatigue level. The algorithm's goal is to identify and treat all patients with fatigue that causes distress or interferes with daily activities or functioning. Management of fatigue begins with primary oncology team members who perform the initial screening and either provide basic education and counseling or expand the initial screening to a more focused evaluation for moderate or higher levels of fatigue. At this point the patient is assessed for the five primary factors known to be associated with fatigue: pain, emotional distress, sleep disturbance, anemia, and hypothyroidism. If any of these conditions are present, it should be treated according to practice guidelines, and the patient's fatigue should be reevaluated regularly. If none of the primary factors is present or the fatigue is unresolved, a more comprehensive assessment is indicated--with referral to other care providers as appropriate. The comprehensive assessment should include a thorough review of systems, review of medications, assessment of comorbidities, nutritional/metabolic evaluation, and assessment of activity level. Management of fatigue is cause-specific when conditions known to cause fatigue can be identified and treated. When specific causes, such as infection, fluid and electrolyte imbalances, or cardiac dysfunction, cannot be identified and corrected, nonpharmacologic and pharmacologic treatment of the fatigue should be considered. Nonpharmacologic interventions may include a moderate exercise program to improve functional capacity and activity tolerance, restorative therapies to decrease cognitive alterations and improve mood state, and nutritional and sleep interventions for patients with disturbances in eating or sleeping. Pharmacologic therapy may include drugs such as antidepressants for depression or erythropoietin for anemia. A few clinical reports of the use of corticosteroids and psychostimulants suggest the need for further research on these agents as a potential treatment modalities in managing fatigue. Basic to these interventions, the effective management of cancer-related fatigue involves an informed and supportive oncology care team that assesses patients' fatigue levels regularly and systematically and incorporates education and counseling regarding strategies for coping with fatigue (Johnson, 1999), as well as using institutional fatigue management experts for referral of patients with unresolved fatigue.

Exercise↗

Cosmic rays and dosimetry at aviation altitudes.

Recent concerns regarding the effects of the cosmic radiation field at aircraft altitudes on aircrew have resulted in a renewed interest in detailed measurements of the neutral and charged particle components in the atmosphere. CR-39 nuclear track detectors have been employed on a number of subsonic and supersonic aircraft to measure charge spectra and LET spectra at aircraft altitudes. These detectors are ideal for long term exposures required for these studies and their passive nature makes them suitable for an environment where interference with flight instrumentation could be a problem. We report here on measurements and analysis of short range tracks which were produced by high LET particles generated mainly by neutron interactions at aviation altitudes. In order to test the overall validity of the technique measurements were also carried out at the CERN-CEC field which simulates the radiation field at aviation altitudes and good agreement was found with dose values obtained using mainly heavy ion calibration.

Aircraft↗

Chronic drinking, binge drinking, and drunk driving II.

Data from the Rhode Island Behavioral Risk Factor Survey on self-reported alcohol consumption and drunk driving were examined. Driving while intoxicated was significantly associated with both binge drinking and chronic drinking, but the measures of drinking were not significantly associated.

Alcohol Drinking↗