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Biomedical subjects

D Kelly

Publications and source records attributed to D Kelly.

At least 19 recordsLinked to original sources

The effect of fermented liquid feeding on the faecal microbiology and colostrum quality of farrowing sows.

This study investigated the effects of fermented liquid feed (FLF) on the lactic acid bacteria (LAB):Coliform (L:C) ratio in the faeces of farrowing sows and the quality of sow colostrum. Eighteen multiparous sows were randomly allocated to one of three dietary treatments for approximately 2 weeks prior to farrowing and for 3 weeks after parturition. The three dietary treatments were dry pelleted feed (DPF), nonfermented liquid feed (NFLF), and fermented liquid feed (FLF). A rifampicin-resistant mutant of Lactobacillus plantarum was used to ferment liquid feed. Coliforms and lactic acid bacteria (LAB) in the faeces of farrowing sows and piglets were estimated by standard microbiological techniques. Intestinal epithelial cells (IEC-6) and blood lymphocytes were used to evaluate the mitogenic activity of colostral samples taken at parturition. Results demonstrated that while the LAB population was not significantly affected by dietary treatment, significant differences in coliform population were observed in the sow faecal samples taken 7 days after parturition. Faeces excreted from sows fed FLF had significantly (P < 0.001) lower numbers of coliforms than sows fed NFLF or DF. Piglets from sows fed FLF excreted faeces that were higher in LAB (7.7 vs. 7.3 log10 CFU g (-1); P < 0.01) and lower in coliforms (7.5 vs. 8.1 log10 CFU g (-1); P < 0.001) than faeces from the piglets of DF-fed dams. Colostrum from sows fed FLF had a significantly greater (P < 0.001) mitogenic activity on both intestinal cells (IEC-6) (79326 +/- 3069 CPM) and blood lymphocytes (1903 +/- 204 CPM) compared with colostrum from dry feed fed sows (53433 +/- 1568 and 1231 +/- 61.4 CPM, respectively). The combined effects of enhanced maternal/passive immunity and the reduction in the level of environmental contamination with faecal pathogens, achieved by FLF, may be important in achieving improved health status for both sows and piglets.

Animal Feed↗

Capturing the spatial percepts evoked by moving tactile stimuli: a novel approach.

Forced-choice procedures are conventionally used to study the percepts evoked by stimuli that move across the skin and enable an unbiased estimation of subjects' sensory capacities. These procedures, however, require subjects to assign complicated percepts to one of a small number of experimenter-defined response categories, none of which may satisfactorily describe the perceptual experience. To address this limitation, we developed a psychophysical approach, which graphically captures spatial information about a moving stimulus in a holistic manner. Briefly summarized, the stimulus object controlled for location, velocity, direction and distance is moved across the skin of a blind-folded subject, after which the subject draws its path on a life-size, two-dimensional photograph of the body region stimulated. Using this approach, we demonstrated that the drawings contain perceptually relevant information, estimates of direction discrimination and subjective traverse length derived from the drawings closely parallel data obtained with forced-choice and magnitude estimation methods, respectively, and generate comparable psychophysical functions of stimulus velocity. In addition, information is represented in the complex shapes of the curves and in the locations at which they are drawn. Analyses of these latter features support the hypothesis that non-sensory factors (individual subject biases) also affect the drawings.

Adolescent↗

Delayed increase in extracellular glycerol with post-traumatic electrographic epileptic activity: support for the theory that seizures induce secondary injury.

Early post-traumatic seizures occur commonly and may have adverse clinical consequences. In order to determine the significance of post-traumatic seizures, we performed a prospective assessment of the consequences of epileptic activity by assessing the change in extracellular glycerol levels. Glycerol is a marker of cellular membrane breakdown. Thirteen patients underwent combined electroencephalography (EEG) and cerebral microdialysis monitoring. Two patients had seizures on EEG with associated delayed elevations of glycerol associated with the seizure activity. Higher mean levels of glycerol were present in those patients with seizures compared to those without seizures (p < 0.001). Preliminary evidence suggests that post-traumatic seizures lead to additional membrane injury as reflected by elevated extracellular glycerol levels.

Adult↗

Investigation of the effect of FK506 (tacrolimus) and cyclosporin on gingival overgrowth following paediatric liver transplantation.

INTRODUCTION: Gingival overgrowth associated with immunosuppression following liver transplantation is a commonly recognized clinical problem. The aims of this study were to determine the incidence of gingival overgrowth in a group of children post liver transplantation and to compare gingival overgrowth in children receiving FK506 with those receiving cyclosporin. METHODS: Seventy-nine children (aged 15-196 months) undergoing liver transplantation at Birmingham Children's Hospital between October 1998 and October 2000 were studied. Gingival overgrowth was assessed in a blinded fashion and scored in a previously validated manner. Gingival overgrowth scores of the patients on each immunosuppressant drug were then compared. RESULTS: Fifty-two patients were treated with cyclosporin and 27 treated with tacrolimus. Eighteen children were also receiving nifedipine (also known to cause gingival overgrowth) and were considered separately. Of the 41 children receiving cyclosporin alone, 26 exhibited gingival overgrowth compared to zero of 20 patients receiving tacrolimus alone. Those children treated with immunosuppression plus nifedipine developed gingival overgrowth, however, this was much less marked in the tacrolimus group. CONCLUSION: Tacrolimus, unlike cyclosporin, is not associated with gingival overgrowth when used for immunosuppression following liver transplantation in children, and may be the drug of choice for children.

Adolescent↗

Hepatitis C-Z: recent advances.

In this review, recently identified hepatitis viruses (hepatitis C, hepatitis D, hepatitis E, hepatitis F, hepatitis G, transfusion transmissible virus) are described, and the implications for paediatric liver disease discussed.

Antiviral Agents↗

Estimation of the prevalence of diagnosed diabetes from primary care and secondary care source data: comparison of record linkage with capture-recapture analysis.

STUDY OBJECTIVE: To compare multiple source linkage and capture-recapture analysis in determining the current age and gender specific prevalence of type 1 and type 2 diabetes in a UK white population. To assess whole population trends in diabetes prevalence and treatment by comparison with previous studies. DESIGN: Data were obtained from hospital sources and all 74 general practices in the study population. Analyses were carried out both by record linkage and by use of a two source capture-recapture model to correct for incomplete ascertainment. SETTING: County of Clwyd, North Wales: total population 418,200. MAIN RESULTS: By record linkage the age adjusted prevalence of all diabetes was 2.04 (95% confidence intervals 2.00 to 2.09)%. Using the capture-recapture method it was 2.29 (2.24 to 2.33)%. From capture-recapture data the age adjusted prevalence of type 1 diabetes was 0.40 (0.37 to 0.43)% in men and 0.28 (0.25 to 0.30)% in women; the prevalence of type 2 was 2.03 (1.97 to 2.09)% in men and 1.67 (1.62 to 1.72)% in women. These figures represent an increase compared with previous surveys. The age specific prevalence of type 2 diabetes was greater in men in a ratio of approximately 1.5:1 and there were more patients treated by diet alone. CONCLUSIONS: Record linkage using multiple sources underestimates the prevalence of diabetes compared with capture-recapture estimates. The results suggest the prevalence of known diabetes in the UK has approximately doubled in less than 20 years. There is an increasing preponderance of male patients and of patients treated currently with diet alone.

Adolescent↗

A clinical inflammatory syndrome attributable to aerosolized lipid-DNA administration in cystic fibrosis.

Immunologic reactivity to lipid-DNA conjugates has traditionally been viewed as less of an issue than with viral vectors. We performed a dose escalation safety trial of aerosolized cystic fibrosis transmembrane conductance regulator (CFTR) cDNA to the lower airways of eight adult cystic fibrosis patients, and monitored expression by RT-PCR. The cDNA was complexed to a cationic lipid amphiphile (GL-67) consisting of a cholesterol anchor linked to a spermine head group. CFTR transgene was detected in three patients at 2-7 days after gene administration. Four of the eight patients developed a pronounced clinical syndrome of fever (maximum of 103.3EF), myalgias, and arthralgia beginning within 6 hr of gene administration. Serum IL-6 but not levels of IL-8, IL-1, TNF-alpha, or IFN-gamma became elevated within 1-3 hr of gene administration. No antibodies to the cationic liposome or plasmid DNA were detected. We found that plasmid DNA by itself elicited minimal proliferation of peripheral blood mononuclear cells taken from study patients, but led to brisk immune cell proliferation when complexed to a cationic lipid. Lipid and DNA were synergistic in causing this response. Cellular proliferation was also seen with eukaryotic DNA, suggesting that at least part of the immunologic response to lipid-DNA conjugates is independent of unmethylated (E. coli-derived) CpG sequences that have previously been associated with innate inflammatory changes in the lung.

Administration, Inhalation↗

Successful ribavirin therapy for life-threatening laryngeal papillomatosis post liver transplantation.

A 3-yr-old girl developed severe progressive juvenile laryngeal papillomatosis (JLP) 2 yr after liver transplantation (Tx) for biliary atresia. The papillomata were resistant to withdrawal of immunosuppression, to laser surgery, and to subcutaneous interferon (3 MU/m2, three times weekly), necessitating tracheostomy. Oral ribavirin therapy (25 mg/kg/day) in combination with no immunosuppression effectively prevented the rapid recurrence of JLP over 5 yr. Hence, oral ribavirin is a potentially useful therapy in this life-threatening situation and may also be of benefit in other children with severe JLP.

Antiviral Agents↗

'More than just money' -- widening the understanding of the costs involved in cancer care.

AIM: This paper examines the literature relating to the wider concept of cost in cancer care and the implications this has for the development of services particularly within the changing context of cancer care. BACKGROUND: Cancer remains a major cause of morbidity and mortality in the United Kingdom (UK), treatment is often complex and expensive; both in financial and human terms. Service patterns for cancer care are shifting away from traditional inpatient, hospital settings towards short stay/day-care and home care models. This is in response to developments in health care policy, but it is also because of the availability of better tolerated treatments and demand for more patient-focused health care. REVIEW OF THE LITERATURE: The databases of Cinhahl and Medline were accessed using the keywords of costs, treatment, outpatients, home care and cancer. Additional sources of literature were also accessed through hand searching key journals. The paper explores the literature in three themes. First, the cost-effectiveness of cancer treatment; second, the often invisible indirect or 'out of pocket' costs incurred by patients and their families during cancer treatment and finally, the 'human costs' of a cancer diagnosis and cancer therapy. CONCLUSIONS: In view of recent calls to improve the effectiveness of cancer care in the UK, we suggest that research is needed to address all the dimensions of cost. It is only by exploring total costs from this broad perspective that appropriate, effective and holistic services can be planned for the future.

Ambulatory Care↗

Action research in action: reflections on a project to introduce Clinical Practice Facilitators to an acute hospital setting.

AIMS OF THE PAPER: The process and philosophical basis of action research are discussed in this article by reviewing the insights that were gained from a study designed to enhance the support available to junior nursing staff in an acute hospital setting. RATIONALE: It has been well documented that newly qualified nurses require help to develop professional competencies. With this in mind, the role of Clinical Practice Facilitator was established within a National Health Service (NHS) Trust to enhance clinical skill acquisition and the professional development of newly registered nurses and health care assistants. DESIGN: In order to facilitate the inception, development and subsequent evaluation of these new roles, an action research approach was adopted. Strategies used to encourage collaboration and flexibility during the project are also discussed. RESULTS: The primary aims of the project were achieved and the authors suggest that the choice of action research was significant to the successful outcome. However, a number of issues arose which deserve more attention including the importance of the interpersonal skills of the action researcher and the value of action research to facilitate change which is relevant at both an individual and organizational level.

Humans↗

The changing training needs of clinical nurse managers: exploring issues for continuing professional development.

AIMS OF THE STUDY: To identify areas where clinical nurse managers perceived that they would benefit from further training and to make recommendations for planning future programmes to meet their needs. BACKGROUND: The effectiveness of the clinical nurse manager has traditionally been associated with maintaining standards of care. Continuing professional development (CPD) is essential to ensure this important group feel adequately prepared to perform their role and has been recognized as an important factor in maintaining job satisfaction and reducing wasteful staff turnover. A review of the literature indicated that since the 1980s the CPD needs of clinical nurse managers have tended to be overlooked despite increasing complexity of the tasks expected of them. Thus it appeared that a fresh study to address these needs would be justified and should take into account sources of work-related stress and variables relating to job satisfaction. METHODS: The study involved clinical nurse managers employed in all four acute hospital National Health Service (NHS) trusts where training needs were served by a major inner city educational consortium. Data collection proceeded in two stages. Initially interviews were undertaken with a random sample of 15 clinical nurse managers to provide in-depth, qualitative data. This information was used to develop a survey questionnaire distributed to the remaining 182 clinical nurse managers in each of the trusts. RESULTS: Data from the interviews indicated that clinical nurse managers appeared to feel clinically competent but generally experienced lack of confidence when dealing with a range of issues, in particular; human resources, managing budgets, deputizing for senior colleagues across the trust ('acting up') and using information technology in everyday practice. Response rate to the survey was good (65%). The results corroborated the interview findings, indicating a need for updating in the same wide range of topics. There were few differences in training needs across all four trusts. Clinical nurse managers who perceived that they had been well-prepared for their role demonstrated higher levels of job satisfaction. Perceived preparation for clinical leadership was the same irrespective of the employing trust, length of time in post and other sociodemographic variables. CONCLUSIONS: The study findings confirm that CPD remains a major issue for clinical nurse managers in the United Kingdom (UK) and that providing opportunities for such development may be an important factor in enhancing job satisfaction. The study findings should help those providing CPD to plan more effectively for this group and have implications for staff recruitment and retention.

Attitude of Health Personnel↗

Examining the validity of pressure ulcer risk assessment scales: developing and using illustrated patient simulations to collect the data.

Simulations are of particular advantage in research studies where large samples are necessary to achieve statistical power and the information must be collected under uniform conditions in order to aid interpretation. In the study reported below, simulation was achieved through the use of medical photography accompanied by case studies of the same patients. All information was collected on the same day. The purpose of the study was to determine the validity of the three pressure ulcer risk assessment scales most commonly used in clinical nursing practice in the UK. Each clinical nurse assessed the same four patients using three risk assessment scales and a visual analogue scale designed to capture their own clinical judgement. External validity was assessed by a panel of tissue viability experts who provided independent ratings. Data were obtained from 236 clinical nurses, yielding 941 risk assessments. Experience with this approach to data collection suggests that it requires careful planning. This should include measures to ensure that the simulated information is valid and that all data collectors have been adequately trained and are able to motivate the nurses participating in the study. Providing consideration is given to these issues, the use of simulation can help to collect data that would be difficult to obtain by more conventional means. It is also important to recognize that clinical decisions are de-contextualized in simulations because they are reduced to verbal and visual summaries. The decision to use simulations should thus be taken only if this is acknowledged.

Clinical Competence↗

Adjuvant-induced joint inflammation causes very rapid transcription of beta-preprotachykinin and alpha-CGRP genes in innervating sensory ganglia.

Neuropeptides synthesized in dorsal root ganglia (DRG) have been implicated in neurogenic inflammation and nociception in experimental and clinical inflammatory arthritis. We examined the very early changes in response to adjuvant injection in a rat model of unilateral tibio-tarsal joint inflammation and subsequent monoarthritis. Within 30 min of adjuvant injection ipsilateral swelling and hyperalgesia were apparent, and marked increases in beta-preprotachykinin-A (beta-PPT-A) and alpha-calcitonin gene-related peptide (CGRP)-encoding mRNAs were observed in small-diameter L5 DRG neurones innervating the affected joint. This response was augmented by recruitment of additional small-diameter DRG neurones expressing beta-PPT-A and CGRP transcripts. The increased mRNA was paralleled by initial increases in L5 DRG content of the protein products, substance P and calcitonin gene-related peptide. Within 15 min of adjuvant injection there were increases in electrical activity in sensory nerves innervating a joint. Blockade of this activity prevented the rapid induction in beta-PPT-A and CGRP mRNA expression in DRG neurones. Increased expression of heteronuclear (intron E) beta-PPT-A RNA suggests that increases in beta-PPT-A mRNA levels were, at least in part, due to transcription. Pre-treatment with the protein synthesis inhibitor cycloheximide had no effect upon the early rise in neuropeptide mRNAS: This and the rapid time course of these changes suggest that increased sensory neural discharge and activation of a latent modulator of transcription are involved.

Animals↗

Development, analysis, refinement, and utility of an interdisciplinary amyotrophic lateral sclerosis database.

The current status of evaluation and management provided by individual healthcare professionals (HCP) at amyotrophic lateral sclerosis (ALS) centers and clinics needs to be analyzed. This paper describes one ALS center's experiences with the development, analysis, refinement, and utility of an interdisciplinary, HCP-driven ALS database. The purpose and conceptual framework of the database, the general data that needed to be collected, and the types of reports that needed to be generated were determined, and, in collaboration with a computer programmer, data entry and database management systems were developed. Data were collected on 234 patients between September 1996 and August 1998, and were analyzed by a biostatistician. Based on review of the biostatistician's report and discussion of problems encountered with the systems, the database was then refined. Benefits of the database system included: systematization of data collection and reporting, reduction of redundant data collection by individuals, decreased variability of evaluation methods and management decisions from patient to patient, and increased availability of a variety of uniform patient information to assist team members in making care decisions. Ongoing refinement will ensure that this HCP-driven ALS database continues to be informative, practical and effective for decision-making and enhancing delivery of care.

Adult↗

Early diagnosis of scrub typhus with a rapid flow assay using recombinant major outer membrane protein antigen (r56) of Orientia tsutsugamushi.

The variable 56-kDa major outer membrane protein of Orientia tsutsugamushi is the immunodominant antigen in human scrub typhus infections. We developed a rapid immunochromatographic flow assay (RFA) for the detection of immunoglobulin M (IgM) and IgG antibodies to O. tsutsugamushi. The RFA employs a truncated recombinant 56-kDa protein from the Karp strain as the antigen. The performance of the RFA was evaluated with a panel of 321 sera (serial bleedings of 85 individuals suspected of scrub typhus) which were collected in the Pescadore Islands, Taiwan, from 1976 to 1977. Among these 85 individuals, IgM tests were negative for 7 cases by both RFA and indirect fluorescence assay (IFA) using Karp whole-cell antigen. In 29 cases specific responses were detected by the RFA earlier than by IFA, 44 cases had the same detection time, and 5 cases were detected earlier by IFA than by RFA. For IgG responses, 4 individuals were negative with both methods, 37 cases exhibited earlier detection by RFA than IFA, 42 cases were detected at the same time, and 2 cases were detected earlier by IFA than by RFA. The sensitivities of RFA detection of antibody in sera from confirmed cases were 74 and 86% for IgM and IgG, respectively. When IgM and IgG results were combined, the sensitivity was 89%. A panel of 78 individual sera collected from patients with no evidence of scrub typhus was used to evaluate the specificity of the RFA. The specificities of the RFA were 99% for IgM and 97% for IgG. The sensitivities of IFA were 53 and 73% for IgM and IgG, respectively, and were 78% when the results of IgM and IgG were combined. The RFA test was significantly better than the IFA test for the early detection of antibody to scrub typhus in primary infections, while both tests were equally sensitive with reinfected individuals.

Antibody Specificity↗

Epstein-Barr virus infection in paediatric liver transplant recipients: detection of the virus in post-transplant tonsillectomy specimens.

AIMS: Post-transplant lymphoproliferative disease (PTLD) is an important and serious complication in transplant patients. Recent studies have suggested that quantitative assessment of Epstein-Barr virus (EBV) infection in transplant patients might help to identify those at risk of developing PTLD. Therefore, tonsils from paediatric liver transplant recipients were studied for evidence of EBV infection. METHODS: Tonsils were studied by in situ hybridisation for the detection of the small EBV encoded nuclear RNAs (EBERs). The phenotype of EBV infected cells was determined by double labelling in situ hybridisation and immunohistochemistry. The expression of viral latent and lytic antigens was determined by immunohistochemistry. Tonsils from patients without known immune defects were studied as controls. RESULTS: Tonsils from transplant patients showed pronounced follicular hyperplasia and minor paracortical hyperplasia. In situ hybridisation revealed variable numbers of EBV infected B cells in the tonsils from transplant patients (range, 2-1000/0.5 cm(2); mean, 434/0.5 cm(2); median, 105/0.5 cm(2)). Lower numbers were detected in the control tonsils (range, 1-200/0.5 cm(2); mean, 47/0.5 cm(2); median, 9/0.5 cm(2)). The latent membrane protein 1 (LMP1) of EBV was not detected and there were only rare cells in two cases showing expression of the EBV encoded nuclear antigen 2 (EBNA2). There was no evidence of lytic infection. None of the patients developed PTLD within a follow up period of up to five years. CONCLUSIONS: These data indicate that tonsillar enlargement in paediatric liver transplant patients does not necessarily imply a diagnosis of PTLD. Furthermore, the presence of increased numbers of EBV infected cells in tonsils from liver transplant recipients by itself does not indicate an increased risk of developing PTLD.

Antigens, Viral↗

Summative assessment.

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Education, Medical, Graduate↗