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Biomedical subjects

L H Thomas

Publications and source records attributed to L H Thomas.

At least 37 records · Page 2Linked to original sources
PubMed1998

Passive protection of gnotobiotic calves using monoclonal antibodies directed at different epitopes on the fusion protein of bovine respiratory syncytial virus.

Two neutralizing, fusion-inhibiting bovine monoclonal antibodies (MAbs; B4 and B13) directed at different epitopes on the fusion protein of respiratory syncytial virus (RSV) protected the lungs of gnotobiotic calves from RSV infection. The MAbs were administered intratracheally 24 h before the calves were challenged with bovine RSV. A third, nonneutralizing, non-fusion-inhibiting but complement-fixing MAb, B1, provided no significant protection against infection, and the disease was not exacerbated. Pneumonic consolidation and mean virus titer in lung 7 days after challenge were significantly lower in calves given the fusion-inhibiting MAbs than in either control calves or those given MAb B1. The proliferative bronchiolitis with syncytial formation and widespread distribution of RSV antigen in the lower respiratory tract of the B1-treated and control calves were indistinguishable and typical of experimental bovine RSV infection. Syncytia were markedly absent, and little or no viral antigen was detected in either the B4- or B13-treated calves.

Animals↗
PubMed1998

Resistance to bovine respiratory syncytial virus (BRSV) induced in calves by a recombinant bovine herpesvirus-1 expressing the attachment glycoprotein of BRSV.

The ability of a bovine herpesvirus-1 (BHV-1) recombinant expressing the G protein of bovine respiratory syncytial virus (BRSV) to protect against BRSV infection was examined in calves. A synthetic G gene was inserted behind the gE promoter of BHV-1 to give a gE-negative, BHV-1/G recombinant. Gnotobiotic calves, vaccinated intranasally and intratracheally with BHV-1/G were challenged 6 weeks later with the Snook strain of BRSV. As controls, calves were vaccinated with a gE-negative mutant of BHV-1 which contains a frame-shift (BHV-1/gEfs). Whereas infection with BHV-1/gEfs induced only mild clinical signs, infection with BHV-1/G resulted in more severe clinical disease and higher titres of BHV-1/G were isolated from the lungs when compared with BHV-1/gEfs. Thus, expression of the G protein of BRSV increased the virulence of BHV-1 for calves. Vaccination with BHV-1/G induced BRSV-specific antibody in serum and respiratory secretions. However, only one calf developed low levels of BRSV complement-dependent neutralizing antibody. Although BHV-1/G primed calves for BRSV-specific lymphocyte proliferative responses, there was no evidence for priming of BRSV-specific cytotoxic T cells. After challenge with BRSV, there was a significant reduction in nasopharyngeal excretion of BRSV in BHV-1/G-vaccinated calves compared with controls and BRSV was isolated from the lung of only one of five vaccinated calves compared with all four control animals. In addition, the extent of gross pneumonic lesions 7 days after BRSV challenge was significantly reduced in calves vaccinated with BHV-1/G compared with controls given BHV-1/gEfs.

Animals↗
PubMed1998

Activity of the mitogenic Pasteurella multocida toxin requires an essential C-terminal residue.

Pasteurella multocida toxin (PMT) is a potent mitogen that also affects bone resorption. PMT acts intracellularly and is therefore postulated to have several domains involved in different aspects of its function. The toxin contains eight cysteine residues. Mutants with individual substitutions for each of these residues were constructed, and the effects of these on the biological activity of the toxin were determined by cultured-cell assays. Only the most C-terminal of the eight cysteines (C1165) was essential for full activity, although mutation of the cysteine residue at position 1159 caused a slight but reproducible loss of potency. In animal challenge experiments, mutant toxin (C1165S) was not toxic to piglets, even at doses exceeding a lethal dose of active PMT 1, 000-fold. The mutant and wild-type toxins displayed identical purification characteristics, similar susceptibility to proteolytic digestion, and circular dichroism profiles, which indicated that no gross structural changes had taken place. The function of the essential C1165 residue is not yet known, although its most likely role is an enzymatic one at or near the catalytic center of the toxin.

3T3 Cells↗
PubMed1998

Effect of clinical guidelines in nursing, midwifery, and the therapies: a systematic review of evaluations.

BACKGROUND: Although nursing, midwifery, and professions allied to medicine are increasingly using clinical guidelines to reduce inappropriate variations in practice and ensure higher quality care, there have been no rigorous overviews of their effectiveness, 18 evaluations of guidelines were identified that meet Cochrane criteria for scientific rigor. METHODS: Guideline evaluations conducted since 1975 which used a randomised controlled trial, controlled before and after, or interrupted time series design were identified through a combination of database and hand searching. RESULTS: 18 studies met the inclusion criteria. Three studies evaluated guideline dissemination or implementation strategies, nine compared use of a guideline with a no guideline state; six studies examined skill substitution: performance of nurses operating according to a guideline were compared with standard care, generally provided by a physician. Significant changes in the process of care were found in six out of eight studies measuring process and in which guidelines were expected to have a positive impact on performance. In seven of the nine studies measuring outcomes of care, significant differences in favour of the intervention group were found. Skill substitution studies generally supported the hypothesis of no difference between protocol driven by nurses and care by a physician. Only one study included a formal economic evaluation, with equivocal findings. CONCLUSIONS: Findings from the review provide some evidence that care driven by a guideline can be effective in changing the process and outcome of care. However, many studies fell short of the criteria of the Cochrane Effective Practice and Organisation of Care Group (EPOC) for methodological quality.

Allied Health Occupations↗
PubMed1997

Recombinant vaccinia viruses expressing the F, G or N, but not the M2, protein of bovine respiratory syncytial virus (BRSV) induce resistance to BRSV challenge in the calf and protect against the development of pneumonic lesions.

The immunogenicity and protective efficacy of recombinant vaccinia viruses (rVV) encoding the F, G, N or M2 (22K) proteins of bovine respiratory syncytial virus (BRSV) were evaluated in calves, the natural host for BRSV. Calves were vaccinated either by scarification or intratracheally with rVV and challenged 6 to 7 weeks later with BRSV. Although replication of rVV expressing the F protein in the respiratory tract was limited after intratracheal vaccination, the levels of serum and pulmonary antibody were similar to those induced following scarification. The serum antibody response induced by the F protein was biased in favour of IgG1 antibody, whereas the G and the N proteins induced similar levels of IgG1:IgG2, and antibody was undetectable in calves primed with the M2 protein. The F protein induced neutralizing antibodies, but only low levels of complement-dependent neutralizing antibodies were induced by the G protein, and antibody induced by the N protein was not neutralizing. The F and N proteins primed calves for BRSV-specific lymphocyte proliferative responses, whereas proliferative responses were detected in calves primed with the G protein only after BRSV challenge. The M2 protein primed lymphocytes in only one out of five calves. Although there were differences in the immune responses induced by the rVVs, the F, G and N, but not the M2, proteins induced significant protection against BRSV infection and, in contrast with the enhanced lung pathology seen in mice vaccinated with rVV expressing individual proteins of human (H)RSV, there was a reduction in lung pathology in calves.

Animals↗
PubMed1997

The nursing record as a research tool to identify nursing interventions.

This paper describes a study which was designed to test the feasibility of using retrospective case note abstraction of data from nursing records to identify the nursing interventions given to two groups of patients: those who had suffered a myocardial infarction and those who had sustained a fractured neck of femur. The aim of the study was to assess whether the data obtained from the records were an accurate reflection of the nursing care given to patients. This was done by comparing what was recorded in the notes for specific areas of care with what the nursing staff said they did. The specific areas of care for patients suffering a myocardial infarction were: pain, mobility, anxiety, patient education. The specific areas of care for patients sustaining a fractured femur were: pressure areas, pain, nutrition, mobility and rehabilitation, information and teaching. Data were collected in three ways: using a retrospective data abstraction tool to examine the case notes of a particular patient; interviewing a nurse who had looked after the same patient; interviewing a senior ward nurse to obtain information about ward policies and practices to obtain a profile of the care usually given to these groups of patients. In this paper we present some of our findings and discuss the methodological and logistical problems of using this method.

Feasibility Studies↗
PubMed1996

The eosinophil and its role in asthma.

1. The eosinophil is part of the host defence mechanism to parasitic infection, but is also a key cell in many inflammatory disorders. 2. Eosinophils synthesise a range of pro-inflammatory and cytotoxic mediators, such as basic proteins, hydrolytic enzymes, lipid mediators, cytokines, oxygen metabolites and neuropeptides. 3. Eosinophils are recruited to the lung during episodes of asthma. They migrate from the blood vessels into the tissue via a series of interactions between their surface adhesion molecules and endothelial cells or the extracellular matrix. 4. Activation and prolonged survival of eosinophils occurs upon exposure to mediators released from other tissue resident leukocytes, including eosinophils themselves, and from respiratory tract epithelial cells. Release of eosinophilic mediators causes tissue damage and persistent inflammation of the lung. 5. Currently the most effective therapy for asthma lies with anti-inflammatory drugs, of which the main choices are inhaled corticosteroids or cromolyn sodium and nedocromil sodium.

Animals↗
PubMed1996

Influence of selective T-lymphocyte depletion on the lung pathology of gnotobiotic calves and the distribution of different T-lymphocyte subsets following challenge with bovine respiratory syncytial virus.

The depletion of CD8+ T-lymphocytes with a murine monoclonal antibody (mAb) specific for the CD8 molecule delayed the ability of three gnotobiotic calves to clear bovine respiratory syncytial virus (BRSV) from their lungs within 10 days after an experimental challenge with the virus. This protracted infection was associated with an enhanced pneumonic consolidation score (21.6 per cent) compared with seven control calves (7.4 per cent) and a histological lesion of active respiratory epithelial hypertrophy. Three gnotobiotic calves depleted of the CD4+ subpopulation with the appropriate mAb also had enhanced macroscopic lesions (16.6 per cent) but the histological lesion was less active. The depletion of the gamma/delta TCR+ WC1+ subpopulation had no apparent effect on the macroscopic or microscopic pulmonary lesions. Although the depletion of the CD8+ or the CD4+ subpopulations enhanced the pulmonary lesions, no clinical signs of respiratory disease were detected. Immunoperoxidase labelling and image analysis of the lymphocyte subpopulations in lung tissue revealed an increase in the number of CD8+ T cells after the infection of non-depleted, control calves, especially in the lamina propria of the large bronchioles. Calves depleted of individual lymphocyte subsets and infected with BRSV showed no compensatory increase in the remaining subpopulations and no lymphoreticular hyperplasia.

Animals↗
PubMed1996

Identification of potential CTL epitopes of bovine RSV using allele-specific peptide motifs from bovine MHC class I molecules.

Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection in young infants and housed calves. Depletion of CD8+ lymphocytes from calves inhibited their ability to clear the virus from the nasopharynx and lungs. To study these cells further, a cytotoxic T lymphocyte (CTL) assay was established. CTL could be demonstrated in the peripheral blood of gnotobiotic calves 7-10 days post infection (p.i.) with RSV and in lungs 10 days p.i. This response was both MHC-restricted and virus-specific. Following separation of the lung lymphocytes by magnetic activated cell sorting, it was shown that the cytolytic activity was mediated by cells of the CD8+ phenotype. To identify epitopes recognised by bovine CTL, the consensus motifs from MHC class I alleles found in the herd at Compton were identified. cDNA libraries were constructed and screened for full length class I sequences. The isolated cDNA clones were then transfected into mouse P815 cells and the expressed product immunoprecipitated and matched with a serological specificity. The bovine MHC class I molecules were isolated from lysed transfected cells by affinity chromatography, using a monoclonal antibody specific for bovine MHC class I, and bound peptides were separated by reverse-phase HPLC. Analysis of the protein sequences of bovine RSV for the defined motifs has identified potential CTL epitopes.

Alleles↗
PubMed1996

Primary cytotoxic T-cell responses to bovine respiratory syncytial virus in calves.

Bovine respiratory syncytial virus (RSV) is a major cause of respiratory disease in young calves. Recent studies in calves, in which different T-cell subsets were depleted, have shown that CD8+ T cells play a central role in recovery from RSV infection. The present study demonstrates that RSV-specific, major histocompatibility complex-restricted cytotoxic T cells appear in the peripheral blood of gnotobiotic calves 7-10 days after infection with bovine RSV and were also detected in the lungs 10 days after infection. The cytotoxic T lymphocytes (CTL) recognized antigenically distinct strains of bovine RSV. There was no correlation between either the level of CTL activity in the lung or the development of CTL in the peripheral blood and the extent of pneumonic consolidation. The demonstration of CD8+ CTL in the lungs at a time when bovine RSV has been cleared confirms the importance of these cells in recovery from infection.

Animals↗
PubMed1996

Measuring patients' satisfaction with nursing: 1990-1994.

Assessing patients' satisfaction with the care they receive is assuming greater importance in the new-style National Health Service. This paper reviews recent developments in the measurement of patients' satisfaction with nursing, including new approaches and taking into account increased interest in users' opinions. Studies published since 1990 generally demonstrate lack of clarity with regard to the purpose and intent of the study, as well as a lack of conceptual rigour and methodological investment. However, several new approaches were found upon which future nursing research could build.

Humans↗
PubMed1996

Newcastle satisfaction with nursing scales: an instrument for quality assessments of nursing care.

OBJECTIVES: To test the validity and reliability of scales for measuring patients' experiences of and satisfaction with nursing care; to test the ability of the scales to detect differences between hospitals and wards; and to investigate whether place of completion, hospital, or home influences response. DESIGN: Sample survey. SETTING: 20 wards in five hospitals in the north east of England. PATIENTS: 2078 patients in general medical and surgical wards. MAIN MEASURES: Experiences of and satisfaction with nursing care. RESULTS: 75% of patients approached to complete the questionnaires did so. Construct validity and internal consistency were both satisfactory. Both the experience and satisfaction scales were found to detect differences between randomly selected wards and hospitals. A sample of patients (102) were sent a further questionnaire to complete at home. 73% returned this; no significant differences were found in either experience or satisfaction scores between questionnaires given in hospital or at home. CONCLUSION: Scales to measure patients' experiences of and satisfaction with nursing in acute care have been developed and found to be valid, reliable, and able to detect differences between hospitals and wards. Questionnaires can be given before patients leave hospital or at home without affecting scores, but those given at home have a lower response rate.

Data Collection↗
PubMed1996

Effects of integrin clustering on human lung mast cells and basophils.

The interaction of cells with the extracellular matrix can alter cell responses and is regulated by integrins on the cell surface. We used monoclonal antibodies to the VLA-4 integrins CD29 and CD49d followed by an F(ab')2 fragment of rabbit anti-mouse immunoglobulin G1 to crosslink integrins on the surface of human lung mast cells and basophils. Crosslinking either CD29 or CD49d caused a significant histamine release (HR) from the basophils of most asthmatic donors (10 of 14 for CD49d and 7 of 10 for CD29) (HR = 21 +/- 5%, n = 10, P < 0.005 for CD29 and HR = 19 +/- 4%, n = 14, P < 0.01 for CD49d) yet failed to initiate HR from the basophils of non-atopic and atopic donors (HR was 1 +/- 0.5% for CD29 and 1 +/- 0.5% for CD49d, n = 10, P = NS). Crosslinking either CD29 or CD49d also failed to initiate histamine release from human lung mast cells (HR was 1 +/- 1% for CD29 and 2 +/- 1% for CD49d). The basophils of asthmatic donors responded to 100 and 30 micrograms/ml tissue fibronectin (HR = 12 +/- 2% and 10 +/- 3% for 100 and 30 micrograms/ml fibronectin, respectively, n = 18, P < 0.05), whereas basophils of nonasthmatic patients again failed to degranulate (HR was 0 +/- 0.4% and 1 +/- 0.6%, respectively, n = 11, P = NS). In contrast to the basophil, crosslinking of either CD29 or CD49d failed to initiate histamine release in human lung mast cells (HR = 1 +/- 1% for CD29 and 2 +/- 1%, n = 15). Human lung mast cells were also unresponsive to tissue fibronectin (100 and 30 micrograms/ml) (HR = 1 +/- 1%, n = 5). The tyrosine kinase inhibitor, genistein, significantly reduced CD29- and CD49d-induced HR (inhibition = 83 +/- 7% for CD29 and 77 +/- 6% for CD49d, n > or = 5, P < 0.05). A second tyrosine kinase inhibitor, piceatannol, also significantly reduced both CD29- and CD49d-induced HR (inhibition was 62 +/- 19% for CD29 and 56 +/- 14% for CD49d, n = 7, P < or = 0.05). Integrin crosslinking also affected the response to a second, immunoglobulin E (IgE)-dependent stimulus. Both CD29 and CD49d clustering significantly inhibited anti-IgE-induced histamine release from the human basophil. Inhibition was 30 +/- 5%, n = 18, P < or = 0.001 for CD29 versus 40 +/- 6% for CD49d. In summary, we have shown that crosslinking the beta 1 integrins using either monoclonal antibodies or tissue fibronectin can initiate mediator release from the basophils of asthmatic patients by a mechanism which appears to be tyrosine kinase-mediated. In addition, clustering of integrins modulates the response to a second IgE-dependent signal.

Antibodies, Monoclonal↗
PubMed1995

Obtaining patients' views of nursing care to inform the development of a patient satisfaction scale.

Patient satisfaction is increasingly being measured as an indication of the effectiveness of nursing care. At present, however, there are no validated UK scales available specifically addressed to nursing. The aim of the present study was to develop a sensitive, valid and reliable measure of patient satisfaction. This paper describes the first phase of the study, the development of a multidimensional concept of satisfaction from the patients' perspective. Using qualitative methods, patients were interviewed both in hospital and following discharge. Eleven main concepts were identified: nurses' manner, attentiveness, availability, reassurance, individual treatment, openness/informality, information, professionalism, ward organization, nurses' knowledge and ward environment. Beginning with customer-defined values has provided the starting point for the development of a scale to measure patients' satisfaction with nursing using concepts important to patients, rather than hospital personnel or research teams.

Communication↗
PubMed1995

The effectiveness of nursing: a review.

This paper describes the findings of a literature review of the effectiveness of nursing. Three journals were selected in which this type of study was most likely to be published. A diversity of attempts to measure nursing effectiveness with various types of patient was found. Generally, however, there was a lack of rigour in study design and sample sizes were too small to be able to draw conclusions. No studies were found which undertook a cost-effectiveness analysis of nursing interventions. Suggestions for the way forward in measuring nursing effectiveness are given, together with questions to be addressed by nursing research.

Humans↗
PubMed1995

Role of T-lymphocyte subsets in recovery from respiratory syncytial virus infection in calves.

The role of T-cell subsets in respiratory syncytial virus (RSV) infection was investigated by using monoclonal antibodies (MAbs) to selectively deplete gnotobiotic calves of CD4+, CD8+, or WC1+ gamma delta T-cell receptor+ lymphocytes. Injection of these MAbs produced specific reductions of the target cell populations in the circulation and tissues. Ten days after RSV infection, immunoglobulin M (IgM), IgG1, and IgA antibodies were detected in sera and lung washings from control calves. Depletion of CD8+ T cells had no effect on either the serum or local antibody responses to RSV, whereas depletion of CD4+ T cells suppressed the antibody responses in two of three calves. The IgM and IgA responses were significantly increased in the lung washings of calves from which WC1+ T cells were depleted. Depletion of CD4+ or WC1+ T cells caused no significant delay in virus clearance, although an increase in the extent of pneumonic consolidation was observed in anti-CD4-treated calves. Nasopharyngeal excretion of RSV was prolonged in calves depleted of CD8+ T cells, and virus was isolated in high titers from lung washings of these animals 10 days after infection, whereas virus had been cleared from lung washings of all other animals. The delayed virus clearance was associated with an increase in the severity of pneumonic consolidation in three of four of the calves from which CD8+ T cells were depleted. This study shows that CD8+ T cells play a dominant role in the recovery of calves from RSV infection.

Animals↗