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Biomedical subjects

F Stevenson

Publications and source records attributed to F Stevenson.

At least 19 recordsLinked to original sources
PubMed2003

Developing a measure for the appropriateness of prescribing in general practice.

OBJECTIVE: To explore the feasibility of using a broader definition of the appropriateness of prescribing in general practice by developing ways of measuring this broader definition and by identifying possible relationships between different aspects of appropriateness and patient outcomes. DESIGN: A questionnaire study of patients and general practitioners before and after study consultations, supplemented by data collected from patients' medical records and telephone interviews with patients 1 week later. SETTING: General practices in the south of England. PARTICIPANTS: 24 general practitioners and 186 of their consulting patients. MAIN OUTCOME MEASURES: Unwanted, unnecessary, and pharmacologically inappropriate prescriptions; patients' adherence. RESULTS: Before the consultation 42% of patients said they wanted or expected a prescription for their main problem. Prescriptions were written in two thirds (65%) of study consultations, and 7% of these had not been wanted or expected beforehand. Doctors recorded that one in five prescriptions they wrote were not strictly indicated. Of the 92 independent assessments of these prescriptions, four were judged to be inappropriate and in 19 cases the assessors were uncertain. 41% of prescriptions written were wanted, necessary, and appropriate. Subsequently, 18% of patients for whom a prescription had been written were potentially non-adherent and 25% had worries or concerns about their medication. CONCLUSION: The attempt to measure appropriateness of prescribing along the three dimensions of patients', prescribers', and pharmacological perspectives is both feasible and likely to yield valuable insights into the nature of general practice prescribing and patients' use of medicines.

Drug Prescriptions↗
PubMed2001

Heterogeneous response of antimitochondrial autoantibodies and bile duct apical staining monoclonal antibodies to pyruvate dehydrogenase complex E2: the molecule versus the mimic.

The 2-oxo-acid dehydrogenase complexes and, in particular, the E2 component of the pyruvate dehydrogenase complex (PDC) are the target of antimitochondrial antibodies (AMA). More than 95% of primary biliary cirrhosis (PBC) patients have detectable levels of autoantibodies to PDC-E2 and in general these react with a region of the molecule that contains the prosthetic group lipoic acid (LA). LA is vital to the function of the enzyme, although there is conflicting evidence as to whether its presence is required for PDC-E2 recognition by AMA. Some, but not all, monoclonal antibodies (mAbs) to PDC-E2 produce an intense staining pattern at the apical surface of bile duct epithelial cells (BEC) in patients with PBC, and it has been argued that the molecule at the apical surface of PBC bile duct cells is a modified form of PDC-E2 or a cross-reactive molecule, acting as a molecular mimic. Herein, we characterize the epitopes recognized by 4 anti-PDC-E2 mAbs that give apical staining patterns (3 mouse and 1 human). In particular, by using a combination of recombinant antigens, competitive inhibition assays, and a unique peptide-on-bead assay, we determined that these apically staining mAbs recognize 3 or 4 distinct epitopes on PDC-E2. More importantly, this suggests that a portion spanning the entire inner lipoyl domain of PDC-E2 can be found at the BEC apical surface. In addition, competition assays with patient sera and a PDC-E2-specific mAb showed significant epitope overlap with only 1 of the 3 mouse mAbs and showed a differential response to the peptide bound to beads. These findings further highlight the heterogeneous response of patient autoantibodies to the inner lipoyl domain of PDC-E2.

Amino Acid Sequence↗
PubMed1999

Using reflexivity to optimize teamwork in qualitative research.

Reflexivity is often described as an individual activity. The authors propose that reflexivity employed as a team activity, through the sharing of reflexive writing (accounts of personal agendas, hidden assumptions, and theoretical definitions) and group discussions about arising issues, can improve the productivity and functioning of qualitative teams and the rigor and quality of the research. The authors review the literature on teamwork, highlighting benefits and pitfalls, and define and discuss the role for reflexivity. They describe their own team and detail how they work together on a project investigating doctor-patient communication about prescribing. The authors present two reflexive tools they have used and show through examples how they have influenced the effectiveness of their team in terms of process, quality, and outcome.

Communication↗
PubMed1998

Sodium butyrate upregulates Kupffer cell PGE2 production and modulates immune function.

The immunosuppressive effect of portal venous blood transfusions in organ transplantation has been well established and may be mediated by increased Kupffer cell production of the immunosuppressive arachidonic acid metabolite prostaglandin E2 (PGE2). In this study, butyrate, a short-chain fatty acid known to enhance gene transcription, is hypothesized to enhance Kupffer cell PGE2 production by altering cyclooxygenase or phospholipase A2 (PLA2) activity, thus augmenting the immunosuppressive effect of portal venous transfusion. Lewis rats were given a portal venous transfusion of Wistar-Firth blood or saline 1 h prior to Kupffer cell harvest. The in vitro effects of butyrate on Kupffer cell PGE2 production, cyclooxygenase, and PLA2 activity were assessed. Kupffer cell tumor necrosis factor-alpha (TNFalpha) production was also assessed due to its sensitivity to PGE2 and its proinflamatory effects. Kupffer cells from portally transfused animals produced significantly more PGE2 than saline-transfused controls. Addition of butyrate to the culture medium further increased PGE2 production by as much as sevenfold in Kupffer cells of portally transfused animals. Other short-chain fatty acids, propionate and hexanoate, did not increase PGE2 production. Butyrate added to Kupffer cells from transfused animals slightly upregulated inducible cyclooxygenase (COX-2) mRNA levels as measured by both Northern blot and reverse-transcriptase polymerase chain reaction and increased PLA2 activity fivefold as measured by Western blot. Kupffer cell immune function was also affected by in vitro butyrate treatment with a significant decrease in the production of TNFalpha. Thus, butyrate may be a useful immunoregulatory agent in organ transplantation protocols which seek to enhance transcription of immunosuppressive molecules.

Animals↗
PubMed1998

Insight into the origin and clonal history of B-cell tumors as revealed by analysis of immunoglobulin variable region genes.

Recombination of VH, DH and JH genes is a unique first step in normal B-cell development. Subsequent differentiation to a mature plasma cell is accompanied by further events in the Ig genes, including VL-JL joining, somatic hypermutation and isotype switching. Chromosomal changes leading to B-cell tumors can occur at many points in this sequence, and may be partly a consequence of the genetic mobility and mutability permitted in order to generate a diverse antibody repertoire. V genes of neoplastic B cells may reflect the point of maturation reached by the B cell of origin, prior to transformation. Analysis of tumors therefore provides useful information on V-gene patterns in normal B cells, and may add another dimension to classification of B-cell tumors. Transformation may also preserve cell populations normally destined to die by apoptosis. Tumor cells arrested in the site where somatic hypermutation and isotype switch are occurring can still be subject to these processes, and could be influenced by persisting antigen. However, mutation is silenced at the point of exit to the periphery, leading to fixed mutational patterns in tumors of mature B cells. V-gene analysis provides an invaluable tool for understanding the genesis of neoplastic change. It also has a clear clinical relevance in tracking tumor cells, measuring residual disease, and finally in offering the opportunity of developing vaccines for treatment.

Amino Acid Sequence↗
PubMed1998

Correlation of 9G4 idiotope with disease activity in patients with systemic lupus erythematosus.

OBJECTIVE: To compare the levels of the 9G4 idiotope (9G4 Id) in systemic lupus erythematosus (SLE) patients with a detailed disease activity index, the British Isles Lupus Assessment Group (BILAG) index, and serological parameters of disease activity by ds DNA antibody levels and serum C3 concentrations. METHODS: In a cross sectional analysis serum samples from 190 patients with SLE were studied and a further 55 serial bleeds from 14 patients. An enzyme linked immunosorbent assay was used to measure the 9G4 Id, and anti dsDNA and antimyeloperoxidase (MPO) antibodies. The C3 levels were measured by laser nephelometer. RESULTS: Seventy six of 190 (40%) of the patients tested had raised 9G4 Id levels. In the cross sectional study 9G4 Id levels were found to correlate with disease activity in the BILAG cardiovascular/respiratory renal, and haematological systems and with global BILAG score (p < 0.01). In the serial bleeds 9G4 Id levels correlated with anti-dsDNA antibody and C3 levels, but not with anti-MPO antibodies. No correlations were found with treatment. In six cases the 9G4 Id levels correlated well with global BILAG scores and dsDNA antibody levels. In four cases the BILAG global and 9G4 Id levels alone correlated well. CONCLUSIONS: Raised levels of the 9G4 Id are present in a substantial proportion of serum samples from patients with lupus, correlate with various aspects of disease activity in SLE. The Id is detectable on anti-dsDNA antibodies, though it must also be present on other immunoglobulins whose specificities remain unknown.

Antibodies, Antinuclear↗
PubMed1995

Evidence for the overexpression of the VH4-34 (VH4.21) Ig gene segment in the normal adult human peripheral blood B cell repertoire.

The VH4-34 (VH4.21) gene has been repeatedly found to encode monoclonal anti-i/l cold agglutinins and is occasionally used by other autoantibodies with anti-DNA and rheumatoid factor specificity. To understand the basis for the frequent expression of the VH4-34 gene in autoimmunity, we prepared linker-based, amplified C mu and C gamma V gene (cDNA) libraries from the peripheral blood of two healthy adults (PBL-3 and PBL-4). The frequency of VH4 family gene-containing clones was determined with VH family-specific oligonucleotide probes, and by random sequencing we examined the frequency of VH4-34 gene expression among the VH4+ C mu clones. Collectively, these studies suggested that VH4-34 gene expression accounted for 7.8 and 10.3% of all IgM clones in the cDNA libraries of PBL-3 and PBL-4, respectively. In VH4 family-specific libraries prepared from genomic rearranged Ig DNA, the VH4-34 gene was also overrepresented relative to other VH4 family genes. In both the mu-cDNA as well as the rearranged Ig DNA libraries, the VH4-34-expressing clones were 95 to 100% homologous to the germline sequence and contained different CDR3 sequences. By contrast, the VH4-34-expressing C gamma clones showed somatic diversification from germline; in addition, the C gamma clones often had the same CDR3 sequences, suggesting that these clones were derived from either activated B cells or expanded, clonally related B cells. Multiparameter flow cytometric analysis of peripheral blood lymphocytes indicated that 3.2 to 6.2% of mu+CD20+ cells express the VH4-34-related Id 9G4. These current findings are relevant to the interpretation of restricted Ig gene usage reported in monoclonal cold agglutinin disease and other autoimmune disorders.

Adult↗
PubMed1995

The immunoglobulin VH gene, VH4-21, specifically encodes autoanti-red cell antibodies against the I or i antigens.

Most autoanti-red cell antibodies found in patients with cold agglutinin disease are specific for the I or i carbohydrate antigenic determinants. However, antibodies specific for other antigens such as Pr or Sa can also be found, and these are identified by their pattern of reactivity with enzyme-treated red cells. Recently, it has been shown that the vast majority of anti-Ii antibodies react with a monoclonal anti-idiotypic antibody (9G4); this reactivity arises from restriction of the immunoglobulin heavy chains used to encode the antibodies to a single VH4-21 gene, VH4-21. The 9G4 antibody appears specific for this gene product, and we have used it to analyse VH4-21 gene involvement in encoding a spectrum of red cell antibodies of various specificities. The results support the strong association between usage of this gene and anti-Ii specificity and indicate that it is not generally used by other specificities. In particular, it is striking that the unsubstituted type 2 oligosaccharide antigens (I and i) induce a highly restricted autoantibody response very different from that induced by the sialylated type 2 antigens (Sia-b, -1 and 1b). The 9G4 antibody therefore provides a simple tool for discrimination between these autoanti-red cell antibodies, which should be of use in red cell serology.

Adult↗
PubMed1995

Comparison of two cochlear implant speech processors in better versus poorer performers.

The performance and subjective preferences for two different speech-processing strategies, the Speak strategy in the Cochlear Spectra 22 speech processor and the Multipeak (Mpeak) strategy in the Mini Speech Processor (MSP), are compared within two adult patient groups. Ten experienced cochlear implant (CI) users were selected for this study. One group of 5 CI users have significant open-set speech recognition, and the second group consisted of experienced CI users who have little or no open-set speech recognition on standardized tests (< 30% on sentence tests; < 10% on monosyllabic word tests). While only 4 of the 5 users in each group were available to complete this evaluation, suitable comparisons on the Speak and Mpeak strategies on test performance were possible within each patient group. The performance tests were necessarily different to suit each patient group; however, general trends of test scores and subjective evaluations of each speech processor are compared between these two groups. While the performance scores and subjective ratings consistently favored the Speak strategy in the first group of users, with good open-set speech recognition, the results within the second group were more variable. These findings have significant implications for individual patient and processor selection.

Cochlear Implants↗
PubMed1993

Expression of conformationally constrained adhesion peptide in an antibody CDR loop and inhibition of natural killer cell cytotoxic activity by an antibody antigenized with the RGD motif.

We report that an antibody engineered to express three Arg-Gly-Asp (RGD) repeats in the third complementarity-determining region of the heavy chain (antigenized antibody) efficiently inhibits the lysis of human erythroleukemia K-562 cells by natural killer (NK) cells. Synthetic peptides containing RGD did not inhibit. Inhibition was specific for the (RGD)3-containing loop and required simultaneous occupancy of the Fc receptor (CD16) on effector cells. The antigenized antibody inhibited other forms of cytotoxicity mediated by NK cells but not cytotoxicity mediated by major histocompatibility complex-restricted cytotoxic T lymphocytes (CTL). A three-dimensional model of the engineered antibody loop shows the structure and physicochemical characteristics probably required for the ligand activity. The results indicate that an RGD motif is involved in the productive interaction between NK and target cells. Moreover, they show that peptide expression in the hypervariable loops of an antibody molecule is an efficient procedure for stabilizing oligopeptides within a limited spectrum of tertiary structures. This is a new approach towards imparting ligand properties to antibody molecules and can be used to study the biological function and specificity of short peptide motifs, including those involved in cell adhesion.

Amino Acid Sequence↗
PubMed1993

Identification of the 9G4 idiotope in systemic lupus erythematosus.

An idiotope designated 9G4 (9G4Id) is known to be a marker for immunoglobulins which utilize a particular VH gene, VH4-21. The idiotope has been found to be present on anti-DNA antibodies, and have been identified in 45% of sera from patients with SLE. This idiotope is strongly associated with lupus being very uncommon amongst the other autoimmune rheumatic diseases tested. This distinction is unlike virtually any of the other DNA antibody idiotypes described which are much more widely distributed. 9G4Id levels were found to fluctuate with disease activity in some lupus patients and this idiotope was detected in 3/11 SLE renal biopsies tested. Its presence is associated with the HLA markers A1 and B8 and raised 9G4Id levels are not simply a reflection of hypergammaglobulinaemia. Thus a new DNA antibody associated idiotope has been identified. Expression of the idiotope indicates that a notable proportion of anti-DNA antibodies have VH segments encoded by the same, or closely related genes, and that these restricted immunoglobulins are involved in the renal pathology found in SLE.

Humans↗