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R Pope

Publications and source records attributed to R Pope.

At least 19 recordsLinked to original sources
PubMed2003

A dissection and computer tomograph study of tarsal coalitions in 100 cadaver feet.

Most of the clinical studies report the incidence of tarsal coalitions (TC) as less than 1% but they disregard the asymptomatic coalitions. TC have been associated with degenerative arthritic changes. After X-rays, computer tomography (CT) is the most commonly used diagnostic test in the detection of TC. The aims of our study were to establish the incidence of TC; the association between TC and accessory tarsal bones and between TC and tarsal arthritis; and to assess the sensitivity of CT as a diagnostic tool in TC. We performed spiral CT scans of 100 cadaver feet (mean age at death 77.7+/-10.4), which were subsequently dissected. The dissections identified nine non-osseous TC: two talocalcaneal and seven calcaneonavicular. There was no osseous coalition. Tarsal arthritis was identified in 31 cases. Both talocalcaneal coalitions were associated with arthritis while none of the calcaneonavicular coalitions were associated with tarsal arthritis. The CT diagnosed an osseous talocalcaneal coalition and was suspicious of fibrocartilaginous coalitions in eight cases. There was correlation between dissection and CT in two talocalcaneal coalitions and three calcaneonavicular coalitions thus CT identifying 55.5% of the coalitions. CT did not diagnose four non-osseous coalitions and diagnosed errouresly four possible coalitions. In conclusion our study demonstrated that the incidence of non-osseous TC is higher than previously thought (12.72%). The calcaneonavicular coalitions are the most common single type (9.09%) and they do not seem to be associated with arthritic changes in the tarsal bones. Our CT results suggest that spiral CT has a low sensitivity in the detection of non-osseous coalitions and questions if multislice CT should be used routinely when TC are suspected.

Adult↗
PubMed2001

A genomewide screen in multiplex rheumatoid arthritis families suggests genetic overlap with other autoimmune diseases.

Rheumatoid arthritis (RA) is an autoimmune/inflammatory disorder with a complex genetic component. We report the first major genomewide screen of multiplex families with RA gathered in the United States. The North American Rheumatoid Arthritis Consortium, using well-defined clinical criteria, has collected 257 families containing 301 affected sibling pairs with RA. A genome screen for allele sharing was performed, using 379 microsatellite markers. A nonparametric analysis using SIBPAL confirmed linkage of the HLA locus to RA (P < .00005), with lambdaHLA = 1.79. However, the analysis also revealed a number of non-HLA loci on chromosomes 1 (D1S235), 4 (D4S1647), 12 (D12S373), 16 (D16S403), and 17 (D17S1301), with evidence for linkage at a significance level of P<.005. Analysis of X-linked markers using the MLOD method from ASPEX also suggests linkage to the telomeric marker DXS6807. Stratifying the families into white or seropositive subgroups revealed some additional markers that showed improvement in significance over the full data set. Several of the regions that showed evidence for nominal significance (P < .05) in our data set had previously been implicated in RA (D16S516 and D17S1301) or in other diseases of an autoimmune nature, including systemic lupus erythematosus (D1S235), inflammatory bowel disease (D4S1647, D5S1462, and D16S516), multiple sclerosis (D12S1052), and ankylosing spondylitis (D16S516). Therefore, genes in the HLA complex play a major role in RA susceptibility, but several other regions also contribute significantly to overall genetic risk.

Alleles↗
PubMed2001

Woman-centred care.

Changes over the past decade have emphasised the individual service user and their relationship with the health service. Within the maternity services this has been interpreted as woman-centred care a result of key initiatives; the Winterton Report (House of Commons, 1992. Maternity Services. Second Report of the Health Committee (Winterton Report), Vol. 1. HMSO, London) and Changing Childbirth (DoH, 1993a, Changing childbirth: reports of the expert maternity group parts 1 & 2. HMSO, London). Changing Childbirth outlined key principles of the maternity services and the need for the woman (and her partner, if she wishes) to be the focus of care. The key principles are choice, continuity and control. High quality care depends on the recognition of individuals as having unique needs which continues to be reflected within contemporary policy documents (DoH, 1997, The new NHS: modern and dependable. HMSO, London). This paper presents findings related to the provision of woman-centred care from a national research and development study. The study design incorporated (i): a national survey which was undertaken with midwives, midwife supervisors and doctors; and (ii): in-depth case studies in which information was obtained through interviews with midwives, midwife supervisors, educators, managers, doctors and mothers. Midwives, at all levels, are involved in changing maternity service provision and adapting to new systems of care which aim to increase continuity of care and carer for the woman. The researchers sought to understand how woman-centred care was interpreted and experienced in practice. The findings have been used to identify the continuing educational needs of midwives, and to develop an open learning educational package to meet identified need. The curriculum was designed to enhance the move towards the provision of a more integrated woman-centred service.

Adult↗
PubMed2001

Treatment of relapse after autologous blood stem cell transplantation for severe rheumatoid arthritis.

There is little information about the clinical course of patients with rheumatoid arthritis (RA) who relapse after autologous blood stem cell transplantation (ASCT). We describe 6 patients with severe RA who received ASCT in 3 US centers. Duration of followup was between 24 and 42 months posttransplant. Five patients achieved major responses but relapsed 3-22 months posttransplant. Two patients with relapse improved remarkably after restarting disease modifying antirheumatic drugs (DMARD). Two patients developed a mild RA flare at 3 and 5 months posttransplant and improved spontaneously. All 4 patients who improved after an initial disease flare remained highly functional at 14-22 months posttransplant. All patients in this study were anti-tumor necrosis factor (TNF) drug naive; all received a TNF blocker as a second line posttransplant salvage therapy, but only 3 responded. Future ASCT strategies need to focus on improving the durability of the early posttransplant responses.

Adult↗
PubMed2000

Regulation of TNF-alpha expression in normal macrophages: the role of C/EBPbeta.

C/EBPbeta is present in monocytes and macrophages, binds to the proximal region of the TNF-alpha promoter, and contributes to its regulation. This study was performed to characterize the ability of C/EBPbeta to regulate the TNF-alpha gene in myelomonocytic cells and primary macrophages. In transient transfection assays, overexpression of wild type C/EBPbeta resulted in a 3-4-fold activation of a 120 base pair TNF-alpha promoter-reporter construct, while overexpression of a dominant negative (DN) C/EBPbeta inhibited LPS-induced activation. In vitro monocyte-differentiated macrophages, infected with an adenoviral vector expressing the DN C/EBPbeta (AdDNC/EBPbeta) or the control Adbetagal, expressed their transgenes weakly, however expression was greatly enhanced in the presence of PMA. Infection with AdDNC/EBPbeta resulted in 60% suppression of LPS induced TNFalpha secretion compared to Adbetagal infection (P<0.001) in PMA-treated macrophages. Northern blot analysis demonstrated approximately a 40% reduction of the TNF-alpha mRNA in the presence of the DN C/EBPbeta, suggesting that the effect of the DN C/EBPbeta was at the transcriptional level. In contrast, AdDNC/EBPbeta infection did not result in inhibition of LPS-induced TNF-alpha secretion in the absence of PMA. Further, DN versions of both C/EBPbeta and c-Jun, but not NF-kappaB p65, suppressed PMA-induced TNF-alpha secretion in macrophages. These observations demonstrate that, C/EBPbeta and c-Jun contribute to the regulation of the TNF-alpha gene in normal macrophages following treatment with PMA.

Adenoviridae↗
PubMed2000

Quality assurance for nursing and midwifery education: an analysis of the approach in England.

The main purpose of this paper is to discuss conceptual and policy developments for external quality assurance for nurse and midwifery education in England. The current framework was implemented in the academic year 1998/99, and is the subject of a three year evaluation commissioned by the English National Board for Nursing, Midwifery & Health Visiting (ENB). The methods which are being used to evaluate the quality assurance arrangements will be discussed within the context of nursing and midwifery education and practice. The ultimate aim of professionally accredited nursing and midwifery education is to ensure the development of practitioners who are fit for purpose, practice and award. It follows that the quality assurance processes should have the capacity to demonstrate the extent to which professional education meets this aim. This paper will discuss this issue, with particular emphasis on the collaborative review process which is being undertaken by the Quality Assurance Agency and the statutory body for nursing, midwifery and health visiting education. The paper concludes with a discussion of the changes proposed by the government for nursing and midwifery education, and considers the potential impact for quality assurance of health care education.

Curriculum↗
PubMed1999

Autologous hematopoietic stem cell transplantation in refractory rheumatoid arthritis: sustained response in two of four patients.

OBJECTIVE: To investigate the safety and efficacy of immune ablation with subsequent autologous hematopoietic stem cell transplantation (HSCT) in severe rheumatoid arthritis (RA). METHODS: Four patients with refractory RA and poor prognostic indicators were treated. Stem cells were collected and lymphocytes were depleted by 2.3-4.0 logs. The conditioning regimen included cyclophosphamide (200 mg/kg), antithymocyte globulin (90 mg/kg), and, for 1 patient, total body irradiation (TBI) with 400 cGy. Improvement was evaluated according to the American College of Rheumatology (ACR) preliminary definition of improvement in RA (ACR 20), and also according to the ACR 50 and ACR 70 criteria. RESULTS: HSCT was well tolerated. Three patients fulfilled the ACR 70 criteria at 1 month and 3 months post-HSCT. One patient did not fulfill the ACR 20 criteria because of persistent joint tenderness, despite improvement of the joint swelling. At 6 months post-HSCT, 1 patient fulfilled the ACR 70 criteria and 1 fulfilled the ACR 50 criteria, and these 2 patients fulfilled the ACR 70 criteria at 9 months post-HSCT. The other 2 patients (including the patient who received TBI) did not meet the ACR 20 criteria at 6 months and 9 months post-HSCT. The only patient with followup of >9 months fulfilled the ACR 70 criteria at 20 months post-HSCT. CONCLUSION: In this series, autologous HSCT was safe and effective in inducing major clinical response and maintained significant benefit for 2 patients at 9 months and 20 months posttreatment, respectively. Sustained response did not occur for 2 of 4 patients. A regimen dose-response effect may exist, but the addition of TBI did not prevent disease relapse for 1 of the patients. More aggressive T cell depletion of the autograft, use of a myeloablative regimen, or use of an allograft may be necessary to decrease relapse rates.

Adult↗
PubMed1998

Treatment of autoimmune disease by intense immunosuppressive conditioning and autologous hematopoietic stem cell transplantation.

Multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis are immune-mediated diseases that are responsive to suppression or modulation of the immune system. For patients with severe disease, immunosuppression may be intensified to the point of myelosuppression or hematopoietic ablation. Hematopoiesis and immunity may then be rapidly reconstituted by reinfusion of CD34(+) progenitor cells. In 10 patients with these autoimmune diseases, autologous hematopoietic stem cells were collected from bone marrow or mobilized from peripheral blood with either granulocyte colony-stimulating factor (G-CSF) or cyclophosphamide and G-CSF. Stem cells were enriched ex vivo using CD34(+) selection and reinfused after either myelosuppressive conditioning with cyclophosphamide (200 mg/kg), methylprednisolone (4 g) and antithymocyte globulin (ATG; 90 mg/kg) or myeloablative conditioning with total body irradiation (1,200 cGy), methylprednisolone (4 g), and cyclophosphamide (120 mg/kg). Six patients with multiple sclerosis, 2 with systemic lupus erythematosus, and 2 with rheumatoid arthritis have undergone hematopoietic stem cell transplantation. Mean time to engraftment of an absolute neutrophil count greater than 500/microL (0.5 x 10(9)/L) and a nontransfused platelet count greater than 20,000/microL (20 x 10(9)/L) occurred on day 10 and 14, respectively. Regimen-related nonhematopoietic toxicity was minimal. All patients improved and/or had stabilization of disease with a follow-up of 5 to 17 months (median, 11 months). We conclude that intense immunosuppressive conditioning and autologous T-cell-depleted hematopoietic transplantation was safely used to treat these 10 patients with severe autoimmune disease. Although durability of response is as yet unknown, all patients have demonstrated stabilization or improvement.

Activities of Daily Living↗
PubMed1998

Tumor necrosis factor alpha gene regulation: enhancement of C/EBPbeta-induced activation by c-Jun.

Tumor necrosis factor alpha (TNF alpha) is a key regulatory cytokine whose expression is controlled by a complex set of stimuli in a variety of cell types. Previously, we found that the monocyte/macrophage-enriched nuclear transcription factor C/EBPbeta played an important role in the regulation of the TNF alpha gene in myelomonocytic cells. Abundant evidence suggests that other transcription factors participate as well. Here we have analyzed interactions between C/EBPbeta and c-Jun, a component of the ubiquitously expressed AP-1 complex. In phorbol myristate acetate (PMA)-treated Jurkat T cells, which did not possess endogenous C/EBPbeta, expression of c-Jun by itself had relatively little effect on TNF alpha promoter activity. However, the combination of C/EBPbeta and c-Jun was synergistic, resulting in greater than 130-fold activation. This effect required both the leucine zipper and DNA binding domains, but not the transactivation domain, of c-Jun, plus the AP-1 binding site centered 102/103 bp upstream of the transcription start site in the TNF alpha promoter. To determine if C/EBPbeta and c-Jun might cooperate to regulate the cellular TNF alpha gene in myelomonocytic cells, U937 cells that possess endogenous C/EBPbeta and were stably transfected with either wild-type c-Jun or the transactivation domain deletion mutant (TAM-67) were examined. U937 cells expressing ectopic wild-type c-Jun or TAM-67 secreted over threefold more TNF alpha than the control line in response to PMA plus lipopolysaccharide. Transient transfection of the U937 cells expressing TAM-67 suggested that TAM-67 binding to the -106/-99-bp AP-1 binding site cooperated with endogenous C/EBPbeta in the activation of the -120 TNF alpha promoter-reporter. DNA binding assays using oligonucleotides derived from the TNF alpha promoter suggested that C/EBPbeta and c-Jun interact in vitro and that the interaction may be DNA dependent. Our data demonstrate that the TNF alpha gene is regulated by the interaction of the ubiquitous AP-1 complex protein c-Jun and the monocyte/macrophage-enriched transcription factor C/EBPbeta and that this interaction contributes to the expression of the cellular TNF alpha gene in myelomonocytic cells. This interaction was unique in that it did not require the c-Jun transactivation domain, providing new insight into the cell-type-specific regulation of the TNF alpha gene.

CCAAT-Enhancer-Binding Proteins↗
PubMed1992

The psychological costs of screening for cancer.

The benefits of cancer screening programmes accrue to those who have cancer or identifiable precancerous conditions, and in whom the disease progression is slowed or halted by earlier intervention. The costs accrue to the rest of the population for whom there is no direct benefit to health. Attention has been given to the medical risks of screening procedures and to the economic costs, but there has been very little regard paid to the psychological costs. The aim of this paper is to evaluate the psychological impact of screening. Screening participants who are found to have untreatable disease, or for whom the interventions prove ineffective, have a greater proportion of their life as a cancer patient with all the associated psychological (and perhaps physical) distress, but no increase in their life expectancy. Those who receive false positive results may experience acute psychological distress produced by the prospect of a grave diagnosis before they are found to be free from serious disease. Even the procedure of screening itself, with the disturbance of the invitation, the discomfort of the tests and the wait for the diagnosis, can have a significant impact upon some patients. This paper evaluates the psychological costs which may be involved across the whole screening procedure, from the possible alarm of receiving an invitation to participate in screening, to the trauma of a cancer diagnosis for someone who had been unaware of any symptoms.

Adaptation, Psychological↗
PubMed1990

Time-management study of trauma resuscitation.

A prospective time-management analysis of trauma resuscitation (TR) of 431 patients arriving at a university trauma center documents timing and organization. Severity of injury, patient age, and potential airway injury were significant factors increasing the duration of TR up to a certain time (36 minutes). Moderately injured patients required less time (under 25 minutes). Patients needing emergent operations spent a minimal amount of time (20 minutes) in TR. Potential injuries involving the airway or cervical spine, or shock, added minutes. A review of the timing and organization of TR suggests the need for improvement in airway assessment and management. Patients with certain mechanisms of injury and elderly patients with blunt injuries required additional time in TR. With surgery faculty supervision and senior resident attendance, the month of resident experience had no effect on TR times. A timely and organized TR is critical to trauma care. TR times should be documented for quality assurance and ongoing review.

Adolescent↗
PubMed1989

Thyroglobulin antibodies in Graves' disease are associated with T-cell receptor beta chain and major histocompatibility complex loci.

We have investigated the T-cell antigen receptor constant beta and alpha chain genes (TCR-C beta, -C alpha) and the immunoglobulin (Ig) heavy chain switch regions of patients with Graves' disease (GD) using restriction fragment length polymorphism (RFLP) analysis. No significant associations were found with RFLPs of either the TCR-C beta, -C alpha or Ig heavy chain switch region loci and GD. However, a significant association was found between the presence of anti-thyroglobulin (anti-Tg) antibodies in the serum of patients and the 10.0; 9.2 kb TCR-C beta genotype (P less than 0.02). Also, those patients with anti-Tg antibodies had an increased frequency of HLA-DR3 (P less than 0.025). These results suggest that genes residing in the TCR chain and major histocompatibility complex loci may be important in determining the immune response to thyroglobulin but not to the disease itself.

Autoantibodies↗
PubMed1988

Autoantibodies to the thyroid microsomal/thyroid peroxidase antigen are polyclonal and directed to several distinct antigenic sites.

A detailed examination of the epitopes recognized by autoantibodies (aAbs) to the thyroid microsomal antigen/thyroid peroxidase (TMA/TPO) in patients with thyroid autoimmune disease has been made using a combination of immunochemical and enzymatic techniques. Our results demonstrate the the autoimmune response to thyroid microsomal antigen/thyroid peroxidase (TMA/TPO) is multifocal and far more heterogeneous than hitherto recognized. By immunoblotting with aAbs, antigenic determinants on the TMA/TPO have been recognized that are either susceptible to polypeptide denaturation and/or sensitive to the effects of reducing agents. Furthermore, these aAbs can inhibit, to varying degrees, the enzymatic activity of solubilized preparations of TPO in microsomes, as ascertained by peroxidation of guaiacol and iodide. A large proportion of the autoimmune response is directed to the guaiacol peroxidation site. The data support the view that the autoimmune reactivity to the TMA/TPO is a specific polyclonal response with a minimum of six distinct, independent determinants that are recognized by aAbs.

Antigens↗
PubMed1986

Uncrossed complete ureteral duplication with upper system reflux.

We report a case of uncrossed complete ureteral duplication with the orifice of the upper system ureter opening in the cranial and lateral position in the bladder. There was reflux only to the upper system of the duplex kidney, and the patient was treated successfully by conjoint reimplantation of the double ureters.

Child, Preschool↗