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Biomedical subjects

A Edwards

Publications and source records attributed to A Edwards.

At least 91 records · Page 5Linked to original sources
PubMed1999

Human brain activation under controlled thermal stimulation and habituation to noxious heat: an fMRI study.

Brain activity was studied with functional magnetic resonance imaging (fMRI) following thermal stimulation. Two groups (n = 6/group) of human male volunteers were given up to four noxious (46 degrees C) and four non-noxious (41 degrees C) stimuli. In the 46 degrees C experiment, positive signal changes were found in the frontal gyri, anterior and posterior cingulate gyrus, thalamus, motor cortex, somatosensory cortex (SI and SII), supplementary motor area, insula, and cerebellum. Low-level negative signal changes appeared in the amygdala and hypothalamus. All regions activated by 46 degrees C were also activated by 41 degrees C. However, except for SI and thalamus, significantly more activation was observed for the 46 degrees C stimulus. A significant attenuation of the signal change was observed by the third stimulus for the 46 degrees C, but not for 41 degrees C experiment. Similar findings were replicated in the second group. These fMRI findings specify differences between somatosensory and pain sensation and suggest a number of rich avenues for future research.

Adult↗
PubMed1999

The opioid contract in the management of chronic pain.

Although the "opioid contract" is widely used in the administration of chronic opioid therapy, its use has not been well defined and there are few guidelines for developing or revising such tools. We reviewed opioid contracts from 39 major academic pain centers and analyzed every statement for its core meaning. These statements were grouped into general categories and then into specific statement groups. Substantial diversity in the content of the 39 contracts was found. Statements could be grouped into 12 general categories, 43 statements groups, and 125 individual statements. Each of the 39 contracts reviewed contained 22.5% +/- 10.9% of the entire list of 125 statements and 32.6% +/- 11.2% of the 43 statement categories. Contract length averaged less than 3 pages (range: 1 to 1 mean 2.2). We describe frequent and infrequent themes that may be well suited for inclusion in any given contract. While there are many significant issues related to the usage of a formal contract in chronic opioid therapy, there was substantial consistency among the contracts in their universal attempts to improve care through dissemination of information, facilitate a mutually agreed-upon course, or enhance compliance. This study serves as an initial step in considering the risk and benefits of an opioid contract as well as its ideal content and presentation.

Analgesics, Opioid↗
PubMed1999

Lichen sclerosus in adult men: a study of HLA associations and susceptibility to autoimmune disease.

Lichen sclerosus is a skin disorder of unknown prevalence affecting both men and women, and several studies have established HLA associations in women with this disease. Autoimmune disease associations in the form of a personal and/or family history of autoimmune disease have also been shown to be related to lichen sclerosus. In this study, we examined 58 men (mean age 38 years) with lichen sclerosus, 39 of whom had histologically proven disease. HLA tissue typing by phototyping was performed on these patients and contrasted with that of 602 control subjects. There was no difference in antigen frequencies of the HLA class I loci. The patient group was found to have an increased frequency of several HLA antigens of the class II loci: DR11, 13 of 58 (22%) patients vs. 75 of 602 (13%) control subjects (P = 0.05); DR12, five of 58 (9%) patients vs. 16 of 602 (3%) control subjects (P = 0.04); DQ7, 26 of 58 (45%) patients vs. 189 of 602 (31%) control subjects (P = 0.05). There were few autoimmune disease associations: two of 58 (3%) patients had a personal history of a different autoimmune disease, two patients were found to have abnormal thyroid function and six of 58 (10%) had a first-degree relative with an autoimmune disease. There was no difference in the frequency of the autoimmune haplotype HLA A1, B8, DR3/17, DQ2 compared with the control population. HLA DQ7 has now been shown to occur more frequently in both male and female patients with lichen sclerosus, which may reflect the immunopathogenesis of the disease. Autoimmune disease associations, however, are less common in men with lichen sclerosus.

Adult↗
PubMed1999

Specificity of starch synthase isoforms from potato.

In higher plants several isoforms of starch synthase contribute to the extension of glucan chains in the synthesis of starch. Different isoforms are responsible for the synthesis of essentially linear amylose chains and branched, amylopectin chains. The activity of granule-bound starch synthase I from potato has been compared with that of starch synthase II from potato following expression of both isoforms in Escherichia coli. Significant differences in their activities are apparent which may be important in determining their specificities in vivo. These differences include affinities for ADPglucose and glucan substrates, activation by amylopectin, response to citrate, thermosensitivity and the processivity of glucan chain extension. To define regions of the isoforms determining these characteristic traits, chimeric proteins have been produced by expression in E. coli. These experiments reveal that the C-terminal region of granule-bound starch synthase I confers most of the specific properties of this isoform, except its processive elongation of glucan chains. This region of granule-bound starch synthase I is distinct from the C-terminal region of other starch synthases. The specific properties it confers may be important in defining the specificity of granule-bound starch synthase I in producing amylose in vivo.

Amino Acid Sequence↗
PubMed1999

Ectopic pituitary with pregnancy changes in a benign cystic teratoma of the ovary.

We report on the rare finding of pituitary tissue, including both adenohypophysis and neurohypophsis, in a mature cystic teratoma of the ovary removed from a 26 year old female at the time of cesarean section. Immunocytochemistry of the ectopic anterior pituitary component showed pregnancy-related changes that have previously only been described in pituitaries obtained at autopsy.

Adrenocorticotropic Hormone↗
PubMed1999

Transplacental flecainide therapy for fetal supraventricular tachycardia in a twin pregnancy.

We present the case of a twin pregnancy in which 1 fetus developed hydrops secondary to supraventricular tachycardia at 30 weeks' gestation. Transplacental flecainide administration successfully treated the condition without evidence of maternal or fetal side-effects. The case raises ethical and possibly legal issues that present when 1 fetus in a twin pregnancy develops a condition the management of which could cause complications to the other twin and/or the mother.

Adult↗
PubMed1999

Five case studies of soldiers with painful clavicular fracture non-union.

We report a short case series of 5 servicemen who had sustained closed clavicular fractures, 4 of whom presented to our clinic with a painful non-union, and 1 required primary fixation for tenting of the skin. Our treatment consisted of open reduction and internal fixation of these non-unions. This resulted in all these men returning to duties with painfree shoulder girdles within 6 months. A complication in these cases was one of a prominent plate which rubbed on straps and required removal of the plate after union had occurred resulting once again in a painfree shoulder girdle and a return to full duties. We advocate early orthopaedic referral in cases of painful clavicular non-union and where appropriate, open reduction and internal fixation with the expectation of an early return to full duties with a pain free shoulder girdle.

Adult↗
PubMed1999

Ultrastructural model for size selectivity in glomerular filtration.

A theoretical model was developed to relate the size selectivity of the glomerular barrier to the structural characteristics of the individual layers of the capillary wall. Thicknesses and other linear dimensions were evaluated, where possible, from previous electron microscopic studies. The glomerular basement membrane (GBM) was represented as a homogeneous material characterized by a Darcy permeability and by size-dependent hindrance coefficients for diffusion and convection, respectively; those coefficients were estimated from recent data obtained with isolated rat GBM. The filtration slit diaphragm was modeled as a single row of cylindrical fibers of equal radius but nonuniform spacing. The resistances of the remainder of the slit channel, and of the endothelial fenestrae, to macromolecule movement were calculated to be negligible. The slit diaphragm was found to be the most restrictive part of the barrier. Because of that, macromolecule concentrations in the GBM increased, rather than decreased, in the direction of flow. Thus the overall sieving coefficient (ratio of Bowman's space concentration to that in plasma) was predicted to be larger for the intact capillary wall than for a hypothetical structure with no GBM. In other words, because the slit diaphragm and GBM do not act independently, the overall sieving coefficient is not simply the product of those for GBM alone and the slit diaphragm alone. Whereas the calculated sieving coefficients were sensitive to the structural features of the slit diaphragm and to the GBM hindrance coefficients, variations in GBM thickness or filtration slit frequency were predicted to have little effect. The ability of the ultrastructural model to represent fractional clearance data in vivo was at least equal to that of conventional pore models with the same number of adjustable parameters. The main strength of the present approach, however, is that it provides a framework for relating structural findings to the size selectivity of the glomerular barrier.

Animals↗
PubMed1999

Survey of risk behaviour and HIV prevalence in an English prison.

An anonymous, voluntary, linked cohort study was undertaken to determine the prevalence of HIV infection and identify risk factors for the spread of infection in an English prison. Three hundred and seventy-eight (68%) of the inmates participated. The HIV point prevalence was 0.26%. Injecting drug use (IDU) was the most significant HIV risk factor within 20% admitting IDU at any time, of whom 58% injected whilst in prison. Of those injecting in prison 73% shared needles. Two inmates admitted having sex with a male partner in prison. This study demonstrates that the potential exists in this setting for an outbreak of blood-borne virus infection; hepatitis B virus (HBV), hepatitis C virus (HCV) and HIV infection. Injecting drug use and needle sharing represent the greatest risk.

Adult↗
PubMed1999

Shared decision-making in primary care: the neglected second half of the consultation.

The second half of the consultation is where decisions are made and future management agreed. We argue that this part of the clinical interaction has been 'neglected' during a time when communication skill development has been focused on uncovering and matching agendas. There are many factors, such as the increasing access to information and the emphasis on patient autonomy, which have led to the need to give more attention to both the skills and the information required to appropriately involve patients in the decision-making process. This analysis, based on a literature review, considers the concept of 'shared decision-making' and asks whether this approach is practical in the primary care setting. This study, and our ongoing research programme, indicates that future developments in this area depend on increasing the time available within consultations, require improved ways of communicating risk to patients, and an acquisition of new communication skills.

Ethics, Medical↗
PubMed1998

Display of functional alphabeta single-chain T-cell receptor molecules on the surface of bacteriophage.

The ability to display functional T-cell receptors (TCR) on the surface of bacteriophage could have numerous applications. For instance, TCR phage-display could be used to develop new strategies for isolating TCRs with unique specificity or it could be used to carry out mutagenesis studies on TCR molecules for analyzing their structure-function. We initially selected a TCR from the murine T-cell hybridoma, DO11.10, as our model system, and genetically engineered a three domain single-chain TCR (scTCR) linked to the gene p8 protein of the Escherichia coli bacteriophage fd. Immunoblotting studies revealed that (1) E. coli produced a soluble scTCR/p8 fusion protein and (2) the fusion protein was packaged by the phage. Cellular competition assays were performed to evaluate the functionality of the TCR and showed the DO11.10 TCR-bearing phage could significantly inhibit stimulation of DO11.10 T hybridoma cells by competing for binding to immobilized MHC/peptide IA(d)/OVA(323-339). Flow cytometric analysis was carried out to evaluate direct binding of DO11.10 TCR-bearing phage onto the surface of cells displaying either IAd containing irrelevant peptide or OVA peptide. The results revealed binding of DO11.10 TCR-bearing phage only on cells expressing IA(d) loaded with OVA peptide showing TCR fine specificity for peptide. To illustrate the generality of TCR phage-display, we also cloned and displayed on phage a second TCR which recognizes a peptide fragment from human tumor suppressor protein p53 restricted by HLA-A2. These findings demonstrate functional TCR can be displayed on bacteriophage potentially leading to the development of novel applications involving TCR phage-display.

Animals↗
PubMed1998

HIV-1 variation diminishes CD4 T lymphocyte recognition.

Effective long-term antiviral immunity requires specific cytotoxic T lymphocytes and CD4(+) T lymphocyte help. Failure of these helper responses can be a principle cause of viral persistence. We sought evidence that variation in HIV-1 CD4(+) T helper epitopes might contribute to this phenomenon. To determine this, we assayed fresh peripheral blood mononuclear cells from 43 asymptomatic HIV-1(+) patients for proliferative responses to HIV-1 antigens. 12 (28%) showed a positive response, and we went on to map dominant epitopes in two individuals, to p24 Gag restricted by human histocompatibility leukocyte antigen (HLA)-DR1 and to p17 Gag restricted by HLA-DRB52c. Nine naturally occurring variants of the p24 Gag epitope were found in the proviral DNA of the individual in whom this response was detected. All variants bound to HLA-DR1, but three of these peptides failed to stimulate a CD4(+) T lymphocyte line which recognized the index sequence. Antigenic variation was also detected in the p17 Gag epitope; a dominant viral variant present in the patient was well recognized by a specific CD4(+) T lymphocyte line, whereas several natural mutants were not. Importantly, variants detected at both epitopes also failed to stimulate fresh uncultured cells while index peptide stimulated successfully. These results demonstrate that variant antigens arise in HIV-1(+) patients which fail to stimulate the T cell antigen receptor of HLA class II-restricted lymphocytes, although the peptide epitopes are capable of being presented on the cell surface. In HIV-1 infection, naturally occurring HLA class II-restricted altered peptide ligands that fail to stimulate the circulating T lymphocyte repertoire may curtail helper responses at sites where variant viruses predominate.

Amino Acid Sequence↗