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Biomedical subjects

S Jordan

Publications and source records attributed to S Jordan.

At least 19 recordsLinked to original sources

Educational input and patient outcomes: exploring the gap.

Over the last two decades, the health care professions in the United Kingdom have seen an unparalleled expansion of continuing professional education (CPE) and development (CPD) programmes; however, there is little empirical evidence that these enhance the care delivered to patients. Further research is also needed to demonstrate that these initiatives are linked to improved patient outcomes. If health care educators are to move towards an 'evidence-based curriculum', some restructuring of courses may be needed. Priorities should be set and decisions made, based on the results of reliable and valid research into the clinical outcomes of CPE. To evaluate courses and demonstrate educational effectiveness solely in terms of student satisfaction is not enough; to survive in the world of evidence-based care, educators must also demonstrate their contribution to clinical effectiveness. However, the neoteric field of impact evaluation lacks not only validated research methods, but also an agreed agenda for future research. Drawing on interviews undertaken with nurses who have participated in education evaluations and the relevant literature, this paper discusses the available data collection instruments and the development of viable research designs and methods, which are urgently needed to assess the outcomes of professional education programmes.

Clinical Nursing Research

Self-Assembly of Trisoligonucleotidyls: The Case for Nano-Acetylene and Nano-Cyclobutadiene.

Rapid cooling is the recipe for the self-assembly of nanostructures from trisoligonucleotidyls, a novel class of branched oligonucleotides whose 3'-termini are connected by a trifunctional linker. The topology of the smallest complex is formally equivalent to the topology of acetylene, if a DNA double strand is envisioned as a C-C bond. The model of nano-acetylene is shown.

Journal Article

The biosciences in the pre-registration nursing curriculum: staff and students' perceptions of difficulties and relevance.

This paper considers the problematic position of the biological sciences in pre-registration nurse education--'The Bioscience Question'. There is no consensus and little research on the appropriate content and depth of bioscience knowledge required by nurses. Attempts to apportion curriculum time for the biosciences are confounded by the difficulty experienced by nursing students with this area. Within one university department, a survey was undertaken to investigate the perceptions of pre-registration students, and their teachers, of the teaching and learning of biological science, in comparison with other areas of the curriculum. Our findings concur with others that the biosciences are a source of disproportionate difficulty and anxiety to nursing students. Among the students, but not the lecturers, there was some, by no means universal, support for the suggestion that these problems could be reduced by a reallocation of curriculum time in favour of the biosciences. Although it was agreed that bioscience theory should be related more closely to nursing practice, there was no evidence that this lessened the students' difficulties with the subject. In contrast to lecturers, students felt the biosciences to be one of the areas of the pre-registration curriculum most relevant to clinical practice.

Adaptation, Psychological

Medication management: an exploratory study into the role of community mental health nurses.

The recent emphasis on community care for those with mental illness has changed working patterns and modified inter-professional role boundaries within multi-disciplinary teams. Clients with serious mental illness are usually prescribed medications, which have a wide range of side effects. However, it is uncertain who is responsible for monitoring clients for the side effects of their medications, ensuring clients' and carers' understandings of their prescribed medications and optimizing compliance with medication. This paper discusses the findings of the first phase of an ongoing study designed to assess the role of community mental health nurses (CMHNs) in managing clients' medication and the provision of appropriate continuing professional education. Our respondents were 14 CMHNs, seven of whom were preparing to undertake a pharmacology module as part of a higher education diploma, and seven who were to act as comparators. Data from questionnaires, interviews and clinical observations were triangulated. All respondents felt that issues surrounding clients' medication were not accorded a sufficiently high profile and that it was, in part, their responsibility to expand their roles to meet these unmet needs of clients. Administering and managing clients' medications were considered to be the main area of 'occupational territory' which distinguished CMHNs from social workers. However, the nurses felt that their practice was limited by lack of appropriate educational preparation.

Community Mental Health Services

Assessing educational effectiveness: the impact of a specialist course on the delivery of care.

An exploratory study was undertaken in South Wales to assess the changes in clinical practice brought about by a specialized pharmacology module designed for Community Mental Health Nurses (CMHNs), in our institution. The respondents were the seven CMHNs who completed the course in 1997 and returned to clinical practice, and seven CMHN comparators, matched on the basis of work experience and location. In order to assess the impact of the module, the practice, attitudes and knowledge of the respondents were investigated before and after the course and 6 months later, using semistructured interviews, nonparticipant observation and questionnaires. The three data sets were analysed using the constant-comparative method, and relevant themes were identified and refined. While we obtained some objective measures of positive educational impact, these should be considered in relation to contextual and confounding variables. Both reported and observed behaviours indicated that the main benefit from the course was increased awareness and monitoring of the side-effects of medication. Respondents had not implemented change uniformly; several factors determined how they modified working practices, including service pressures and the support of colleagues.

Cohort Studies

Managing diabetic foot ulcers.

This article discusses optimal care for a diabetic foot wound including use of a protocol with standards for assessment, treatment, and prevention. Patient and family education is also pivotal to the plan's success.

Community Health Nursing

Wound care for persons with diabetes.

This article addresses local wound care in people with diabetes mellitus. An approach is proposed that uses wound depth and color to determine the goals of local wound treatment. Principles of cleansing, debridement, and the use of moisture retentive dressings are discussed. Infection, a significant problem in the diabetic patient, is addressed as an essential part of local wound care in these patients.

Bandages

Thrombopoietin concentrations are low in patients with cirrhosis and thrombocytopenia and are restored after orthotopic liver transplantation.

BACKGROUND: Thrombocytopenia in cirrhotic patients may be due to deficient production of thrombopoietin. AIMS: To determine the relation between thrombopoietin and thrombocytopenia in cirrhotic patients before and after orthotopic liver transplantation. METHODS: Thrombopoietin concentrations and platelet counts were measured in 43 cirrhotic patients and 21 normal controls and serially for 14 days after transplantation in 23/43 patients. RESULTS: 27 of the 43 patients had thrombocytopenia (platelet count less than 120 x 10(9)/l; group 1) whereas 16 patients had normal platelet count (group 2). Thrombopoietin concentrations were lower in group 1 than in group 2 (92.5 (20.3-286.3) v 226.6 (30.1-848.3) pg/ml, p=0.003) and normal controls (92.5 (20.3-286.3) v 158.3 (22.5-232.9) pg/ml, p=0.028). Post-transplantation thrombopoietin concentrations increased with a peak at day 5. The rise was significant in patients with low pretransplantation platelet count (89.1 (21.29-247.6) to 545.1 (66.2-2569) pg/ml; n=16, p=0.001) but not in those with normal platelet count (262.8 (30.1-848.3) to 315.1 (114-954.6) pg/ml; n=7, p=0.47). No correlation was found pretransplantation between spleen volume and platelet count (r=-0.11, p=0.6) or thrombopoietin concentrations (r=-0.04, p=0.8). However, pretransplantation thrombopoietin concentrations correlated with platelet count (r=0.47, p=0.0015), whereas an inverse correlation was found between peak thrombopoietin concentrations and nadir platelet count (r=-0.41 p=0. 049) post-transplantation. CONCLUSIONS: Inadequate thrombopoietin production may contribute to cirrhotic thrombocytopenia. Thrombopoietin production is restored after liver transplantation leading to the resolution of thrombocytopenia.

Adult

The design and synthesis of potent inhibitors of hepatitis C virus NS3-4A proteinase.

Hepatitis C virus (HCV) is the cause of the majority of transfusion-associated hepatitis and a significant proportion of community-acquired hepatitis worldwide. Infection by HCV frequently leads to persistent infections that result in a range of clinical conditions including an asymptomatic carrier state, severe chronic active hepatitis, cirrhosis and, in some cases, hepatocellular carcinoma. The HCV genome consists of a single-stranded, positive sense RNA containing an open reading frame of approximately 9060 nucleotides. This is translated into a single polyprotein of approximately 3020 amino acids (C-E1-E2-p7-NS2-NS3-NS4A-NS4B-NS5A-NS5B), which in turn is processed by a series of host and viral proteinases into at least 10 cleavage products. The N-terminal portion of the NS3 protein encodes a serine proteinase that is responsible for the cleavage at the NS3-4A, NS4A-4B, NS4B-5A and NS5A-5B junctions. The 54 amino acid NS4A protein is a cofactor that binds to the NS3 protein and enhances its proteolytic activity. This report describes the expression of a recombinant NS3-4A proteinase fusion protein in Escherichia coli and the in vitro characterization of the enzyme activity using synthetic peptide substrates. It then demonstrates how these results were employed to guide the design of potent inhibitors of this enzyme.

Amino Acid Sequence

Low expression of the cell cycle inhibitor p27Kip1 in normal corticotroph cells, corticotroph tumors, and malignant pituitary tumors.

The cell cycle is regulated by a number of inhibitors, including p27Kip1 (p27), which belongs to the kip1 family. By binding to the cyclin/cyclin-dependent kinase complexes, it regulates progression of G1 to S phase in the cell cycle. It has been reported that p27 knockout mice develop multiorgan hyperplasia and intermediate lobe pituitary tumors secreting ACTH. Previously, we and others have been unable to show any consistent change in messenger RNA expression or genomic mutations for p27 in human corticotroph adenomas. However, dysregulation at the protein level has been reported in nonendocrine tumors, and we, therefore, investigated the expression of p27 in a range of benign and metastatic pituitary tumors. We studied a total of 107 pituitaries, including normal pituitary (n = 20), Cushing's disease (n = 21), acromegaly (n = 19), nonfunctioning adenomas (n = 18), prolactinomas (n = 7), TSH-omas (n = 2), FSH-omas (n = 6), aggressive tumors showing invasiveness and recurrence (n = 9), and metastatic pituitary carcinomas (n = 5). Using standard immunohistochemical techniques with a highly specific monoclonal antibody, p27 expression was determined quantitatively as the percentage of cells showing strongly positive, weak, or negative staining. In each sample, approximately 500 cells were analyzed. We also analyzed normal pituitaries using double-labeling for p27 and each of the pituitary hormones to characterize the expression of p27 in each cell type. p27 was expressed in normal pituitary cells; in tumors expressing GH, prolactin, TSH, and FSH; and in aggressive tumors, but markedly reduced expression of p27 was seen in corticotroph tumors and pituitary carcinomas. In the normal pituitary, somatotroph, lactotroph, and thyrotroph cells showed strong p27 staining, whereas normal corticotroph cells showed a much lower level of p27 staining (P < 0.001). Somatotroph, lactotroph, gonadotroph, and thyrotroph adenomas showed a lower level of p27 expression compared with normal somatotrophs (P = 0.02), lactotrophs (P = 0.03), gonadotrophs (P = 0.01), and thyrotrophs, respectively, whereas the lower level of p27 expression present in normal corticotrophs virtually disappeared in corticotroph adenomas (P = 0.001). We conclude that pituitary adenomas show a lower level of p27 protein expression than the normal cells from which they are derived, with malignant transformation leading to complete loss of p27 immunoreactivity. Corticotrophs are quite different to other pituitary cell types in terms of p27 immunoreactivity because both normal and tumorous corticotrophs have low p27 staining, and we speculate that this may relate to their inherent control mechanisms.

Adenoma

A role for maternal serum screening in detecting chromosomal abnormalities in fetuses with isolated choroid plexus cysts: a prospective multicentre study.

A prospective multicentre study was performed to identify patients with fetal choroid plexus cysts and examine the association between choroid plexus cysts and chromosome abnormalities in the context of variables such as maternal age, serum triple-screen results, race, other prenatally-identified fetal anomalies and cyst characteristics. A total of 18 437 scans were performed in 5 centres and 257 fetuses were identified with choroid plexus cysts. Outcome was available on 250 patients, and of these, chromosomal abnormalities were detected in a total of 13 (5.2 per cent) fetuses. 26 patients in the group had additional ultrasound abnormalities, and 8 of these had fetal chromosome abnormalities. Among the 224 patients with isolated choroid plexus cysts, 5 (2.2 per cent) were found to have chromosomal abnormalities. All cases with identified chromosomal abnormalities were associated with an additional risk factor, such as other ultrasound findings, advanced maternal age or abnormal maternal serum triple-screen results.

Adolescent

Prevention and preemptive therapy of postransplant lymphoproliferative disease in pediatric liver recipients.

BACKGROUND: We have previously reported a 10% incidence of posttransplant lymphoproliferative disease (PTLD) in pediatric patients receiving first liver grafts and primarily immunosuppressed with tacrolimus. To decrease the incidence of PTLD, we developed a protocol utilizing preemptive intravenous ganciclovir in high-risk recipients (i.e., donor (D)+, recipient (R)-), combined with serial monitoring of peripheral blood for Epstein Barr virus (EBV) by polymerase chain reaction (PCR). METHODS: Consecutive pediatric recipients of a first liver graft were immunosuppressed with oral tacrolimus (both induction and maintenance), and low-dose prednisone. EBV serologies were obtained at the time of orthotopic liver transplant in recipients and donors. Recipients were divided into groups: group 1, high-risk (D+R-), and group 2, low-risk (D+R+; D-R-; D-R+). In group 1 (high-risk), all patients received a minimum of 100 days of intravenous ganciclovir (6-10 mg/kg/day), while, in group 2 (low-risk), patients received intravenous ganciclovir during their initial hospitalization and then were converted to oral acyclovir (40 mg/kg/day) at discharge. Semiquantitative EBV-PCR determinations were made at 1-2-month intervals. In both groups, patients with an increasing viral copy number by EBV-PCR had tacrolimus levels decreased to 2-5 ng/ml. Tacrolimus was stopped, and intravenous ganciclovir reinstituted for PTLD. A positive EBV-PCR with symptoms, but negative histology, was defined as EBV disease; PTLD was defined as histologic evidence of polyclonal or monoclonal B cell proliferation. RESULTS: Forty children who had survived greater than 2 months were enrolled. There were 18 children in group 1 (high-risk; mean age of 14+/-15 months and mean follow-up time of 243+/-149 days) and 22 children in group 2 (low-risk; mean age of 64+/-65 months and follow-up time of 275+/-130 days). In group 1 (high-risk), there was no PTLD and one case of EBV disease (mononucleosis-like syndrome), which resolved. In group 2 (low-risk), there were two cases of PTLD; both resolved when tacrolimus was stopped. Both children were 8 months old at time of transplant. Neither received OKT3, and they had one and two episodes of steroid-sensitive rejection, respectively. One child had EBV disease (mild hepatitis), which resolved. CONCLUSIONS: Since instituting this protocol, the overall incidence of PTLD has fallen from 10% to 5% for children receiving primary tacrolimus therapy after OLT. No high-risk pediatric liver recipient treated preemptively with intravenous ganciclovir developed PTLD. Both children with PTLD were less than 1 year at OLT and considered low-risk. However, their positive EBV antibody titers may have been maternal in origin and not have offered long-term protection. Serial monitoring of EBV-PCR after pediatric OLT is recommended to decrease the risk of PTLD by allowing early detection of EBV infection, which is then managed by decreasing immunosuppression and continuing intravenous ganciclovir.

Antiviral Agents

Tolerance induction by intrathymic inoculation prevents chronic renal allograft rejection.

BACKGROUND: These experiments investigated the ability of the donor-specific unresponsiveness created by the intrathymic inoculation of donor alloantigen to effectively prevent chronic rejection in an established rat model of chronic renal allograft rejection. METHODS: Three study groups were examined: (1) Allograft controls--F-344 rats received a Lewis renal allograft plus 10 days of low-dose cyclosporine (CsA); (2) isograft controls--F-344 rats received an F-344 renal isograft and low-dose CsA; (3) experimental group--F-344 rats received a T-cell depleted syngeneic bone marrow transplant and intrathymic injection of Lewis bone marrow. Twenty-one days after bone marrow transplant, these animals received a Lewis renal allograft. RESULTS: Allograft controls demonstrated severe parenchymal fibrosis; isograft controls and intrathymic (IT) animals failed to develop this lesion. Immunohistochemical analysis revealed increased CD4+ T cells infiltrating the cortex of the allograft controls. Cytokine interferon-gamma and interleukin-2 transcripts were strongly positive in allograft controls and were absent from isograft controls and IT allografts as determined by reverse transcriptase-polymerase chain reaction. Analysis of tolerant grafts by flow microfluorimetry and genomic DNA amplification could not detect chimerism to a level of < 0.1%. CONCLUSION: IT inoculation of donor alloantigen can confer long-term unresponsiveness and prevent the development of the characteristic lesions of chronic rejection.

Animals

Mutation and expression analysis of the p27/kip1 gene in corticotrophin-secreting tumours.

The molecular mechanisms leading to Cushing's disease are unclear. Inhibitors of cyclin-cyclin dependent kinase (CDK) complexes are regulators of the cell cycle and may function as tumour suppressor genes, many of which have been involved in the pathogenesis of several human malignancies. A member of this family, the p27/kip1 gene, maps to chromosome 12p13 and encodes an inhibitor of several cyclin-CDK complexes; these control the progression of the cell cycle from G1 to S-phase. Complete lack of p27/kip1 function, as occurs in the p27/kip1 'knockout' mouse, produces a complex phenotype associated with the development of pituitary tumours, specifically those of the intermediate lobe corticotrophs. We therefore investigated whether structural and functional abnormalities of the p27/kip1 gene and loss at the chromosome 12p13 region were present in human corticotrophin (ACTH)-secreting pituitary tumours. We studied 21 pituitary tumours, of which 20 were ACTH-secreting (two of these had biochemical and histological features of 'intermediate-lobe' tumours and one was malignant) while the remaining tumour was a prolactinoma; three ectopic secretors of ACTH (two bronchial and one thymic carcinoid); and a non-secretory thymic carcinoid. The whole coding region of the p27/ kip1 gene was screened for mutations by PCR-SSCP analysis and/or direct sequencing, while tumour mRNA expression was analysed by means of a semi-quantitative duplex PCR. Three polymorphic microsatellite markers of the 12p13 region were used to assess loss of heterozygosity (LOH) in 12 samples. Finally, tumour p27/kip1 protein expression was assessed by immunohistochemistry using a monoclonal antibody in 12 samples suitable for analysis. No sequence abnormalities were found in any of the samples other than a previously-described polymorphism. No LOH was observed in the tumours analysed. p27/kip1 mRNA expression was similar in tumour samples in comparison with normal pituitaries. Seven of the eight corticotroph tumours analysed by immunohistochemistry stained positive for p27/kip1, including the intermediate lobe. The only malignant pituitary tumour in the original series showed an absence of staining for p27/kip1. In addition, the three carcinoid tumours studied were negative on immunohistochemistry. Of a further three malignant pituitary tumours assessed, two (including a prolactinoma) were essentially negative, while the third was moderately positive. We conclude that mutations of the p27/kip1 gene, deletions of the 12p13 area or changes in expression, are not a general feature of corticotroph tumours, even those with intermediate lobe characteristics. However, other mechanisms of p27/kip1 inactivation, such as an abnormality at the post-translational level, may be related to more aggressive histological subtypes of ACTH-secreting and possibly other pituitary tumours.

Adrenocorticotropic Hormone

From classroom theory to clinical practice: evaluating the impact of a post-registration course.

This paper is concerned with the translation of bioscience theory into clinical practice. The empirical data form part of an action research study undertaken to investigate the clinical outcomes of the bioscience component of a post-registration, day release diploma in nursing taught in a higher education institution. Evidence for the impact of the course on patient care was collected by academic diary, questionnaire and interview. The triangulated data indicated that by adapting the pedagogic interpretation of the biosciences, it is possible to bridge the theory-practice gap. As a result, some nurses related the substance of the lessons to their patients, in order to bring about improvements in care. This paper examines the reasons behind the successes and failures of this continuing professional education initiative.

Biological Science Disciplines

An in vivo microdialysis study of striatal 6-[18F]fluoro-L-m-tyrosine metabolism.

In vivo brain microdialysis was used to monitor 6-[18F]fluoro-L-m-tyrosine (FMT) uptake and metabolism in the striatum of conscious freely moving rats for 3 hours after FMT injection (25 mg/kg, i.v.). Microdialysate collected 20 to 120 min post-dose, contained FMT at a concentration (0.2 to 0.3 nM) approximately ten-fold below that of its metabolite [18F]fluoro-3-hydroxyphenylacetic acid (FPAC; 3.2 to 3.3 nM). D-amphetamine (2.5 mg/kg, i.p.) injected 120 min after significantly increased microdialysate FPAC (3.27 +/- 0.31 nM to 4.51 +/- 0.45 nM) in control but not reserpinized rats. Taken together these data demonstrate FMT is heavily metabolized following its entry into the striatum yielding FPAC which appears to be stored, at least in part, in reserpine sensitive cytoplasmic vesicles. Presynaptic retention of FPAC may contribute to the preferential accumulation of FMT positron emission tomography (PET) signaling in dopaminergic brain areas.

Animals

Using bioscience knowledge in nursing: actions, interactions and reactions.

This paper draws on empirical data from a study undertaken to explore the outcomes of the applied physiology component of a post-registration diploma in nursing (DN). Most students completing the DN were utilizing their new bioscience knowledge in clinical practice, and reported increased participation in interprofessional discussions and team decisions. Respondents found themselves better able to monitor and evaluate doctors' decisions and this led to friction with some medical colleagues. However, the strongest resistance came from senior nurses, very few of whom had completed advanced nursing courses in bioscience and who were generally unwilling to allow respondents to develop new roles. General managers were also perceived as a major barrier to change. There is little evidence of tangible benefits to the nurses themselves: most saw the DN qualification as a way of protecting their status as professional nurses in the face of managerially driven organizational change, rather than as a route to occupational advancement.

Adult

Thinking of the future and walking back to normal: an exploratory study of patients' experiences during recovery from lower limb fracture.

Admission to hospital following a traumatic lower limb fracture is undoubtedly a stressful life event; however, few studies have detailed this from the patient's perspective. By exploring patients' experiences of hospitalization with lower limb trauma, this study aimed to explicate some of the factors impinging on the recovery trajectory. Patients' perceptions of the events influencing their strategies for coping with stress, hospitalization and temporary incapacity were investigated using a qualitative methodology. A convenience sample of nine patients was recruited from an orthopaedic ward in a district general hospital in Wales. The respondents used health diaries to document their recovery for up to 6 weeks after emergency surgery. These diaries were validated and supplemented by semi-structured interviews. Following their traumatic injuries, our respondents were subjected to a variety of stressors and uncertainties. They coped with this period of uncertainty by positive attempts to gain control over their situations, guided by an over-riding desire to 'return to normal' and assisted by the caring attributes of their nurses. From the experiences and events documented, this study was able to identify several stressors which could have been mitigated by optimization of the technical aspects of care, including the management of pain.

Activities of Daily Living