Runner's knee: what is it and what helps?
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Humans↗
Biomedical subjects
A Edwards
Publications and source records attributed to A Edwards.
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↗
Attention deficit-hyperactivity disorder not just for children anymore.
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Adult↗
Attitudes to the use of health outcome questionnaires.
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Attitude of Health Personnel↗
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↗
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↗
General practitioners' self assessment of knowledge. The vast range of clinical conditions means that doctors cannot know everything.
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Clinical Competence↗
Novel tetranuclear orthometalated complexes of Pd(II) and Pt(II) derived from p-isopropylbenzaldehyde thiosemicarbazone with cytotoxic activity in cis-DDP resistant tumor cell lines. Interaction of these complexes with DNA.
The reaction of p-isopropylbenzaldehyde thiosemicarbazone [p-is.TSCN], 1, with palladium(II) acetate and potassium tetrachloroplatinate yielded two tetrameric orthopalladated isomers, [Pd(p-is.TSCN)]4 (complexes 2 and 3), and the platinum analogue [Pt(p-is.TSCN)]4 (complex 4), respectively. All of these complexes contain the thiosemicarbazone bonded as a terdentate ligand to the metallic atom, through the thiol sulfur, the azomethinic nitrogen and the ortho carbon of the p-isopropylphenyl ring to which the imine group is attached to as deduced from the study of the IR, NMR, and XRD spectra of complexes 2 and 4. Complexes 2 and 4 crystallize in the centrosymmetric monoclinic space group C2/c, with Z = 8. Unit cell parameters for complex 2 are as follows: a = 25.742(5) A, b = 19.560(4) A, c = 24.199(5) A, beta = 101.70(3)o. Unit cell parameters for complex 4 are as follows: a = 25.8728(19) A, b = 19. 5053(14) A, c = 24.0899(16) A, beta = 101.305(2)o. As can be deduced from the NMR study, the palladated isomers 2 and 3 interconvert in DMSO which may be a consequence of the existence in both complexes of a flexible eight-membered ring with alternating Pd-S atoms. The testing of the cytotoxic activity of these compounds against several human and murine cell lines sensitive and resistant to cisplatin (cis-DDP) suggests that compounds 2, 3, and 4 may be endowed with important anticancer properties since they elicit IC50 values in the microM range as does the clinically used drug cis-DDP, and, moreover, they display cytotoxic activity in tumor lines resistant to cis-DDP. The analysis of the interaction of these novel tetrameric cyclometalated compounds with DNA suggests that they form DNA interhelical cross-links.
Animals↗
Acute plasticity in the human somatosensory cortex following amputation.
We studied a patient after amputation of an arm and found that in less than 24 h stimuli applied on the ipsilateral face were referred in a precise, topographically organized, modality-specific manner to distinct points on the phantom. Functional magnetic resonance imaging (fMRI) performed one month later showed that brush-evoked activity in the brain demonstrates objective signal changes which correlate with perceptual changes in the phantom hand. This finding in humans corresponds to the observations of immediate plasticity in cortical pathways described in animals, including primates. The results suggest that reorganization of sensory pathways occurs very soon after amputation in humans, potentially due to the unmasking of ordinarily silent inputs rather than sprouting of new axon terminals.
Adult↗
Visual acuity and visual field impairment in Usher syndrome.
OBJECTIVE: To determine the extent of visual acuity and visual field impairment in patients with types 1 and 2 Usher syndrome. METHODS: The records of 53 patients with type 1 and 120 patients with type 2 Usher syndrome were reviewed for visual acuity and visual field area at their most recent visit. Visual field areas were determined by planimetry of the II4e and V4e isopters obtained with a Goldmann perimeter. Both ordinary and logistic regression models were used to evaluate differences in visual acuity and visual field impairment between patients with type 1 and type 2 Usher syndrome. RESULTS: The difference in visual acuity of the better eye between patients with type 1 and type 2 varied by patient age (P=.01, based on a multiple regression model). The maximum difference in visual acuity between the 2 groups occurred during the third and fourth decades of life (with the type 1 patients being more impaired), while more similar acuities were seen in both younger and older patients. Fifty-one percent (n=27) of the type 1 patients had a visual acuity of 20/40 or better in at least 1 eye compared with 72% (n=87) of the type 2 patients (age-adjusted odds ratio, 3.9). Visual field area to both the II4e (P=.001) and V4e (P<.001) targets was more impaired in the better eye of type 1 patients than type 2 patients. A concentric central visual field greater than 20 degrees in at least 1 eye was present in 20 (59%) of the available 34 visual fields of type 1 patients compared with 70 (67%) of the available 104 visual fields of type 2 patients (age-adjusted odds ratio, 2.9) with the V4e target and in 6 (21%) of the available 29 visual fields of type 1 patients compared with 36 (38%) of the available 94 visual fields of type 2 patients (age-adjusted odds ratio, 4.9) with the II4e target. The fraction of patients who had a visual acuity of 20/40 or better and a concentric central visual field greater than 20 degrees to the II4e target in at least 1 eye was 17% (n=5) in the type 1 patients and 35% (n=33) in the type 2 patients (age-adjusted odds ratio, 3.9). CONCLUSIONS: Visual acuity and visual field area were more impaired in patients with type 1 than type 2 Usher syndrome. Of note, 27 of 53 type 1 (51%) and 87 of 120 type 2 (72%) patients had a visual acuity of 20/40 or better in at least 1 eye. These data are useful for overall counseling of patients with Usher syndrome.
Adult↗
Age-related macular degeneration. Clinical features in a large family and linkage to chromosome 1q.
OBJECTIVES: To identify the chromosomal location of a disease-causing gene and to describe the clinical characteristics of a large family with age-related macular degeneration (ARMD). METHODS: An ARMD pedigree was identified, and the disease state of family members was documented by stereoscopic fundus photography and was classified using a modified version of the Wisconsin Age-Related Maculopathy Grading System. A genome-wide screen at approximately 6-centimorgan spacing using a DNA-pooling strategy combined with shared-segment analysis was used to identify likely chromosomal regions. The entire family was then screened at each likely locus, and 1 positive locus was refined by screening with markers at an average density of 0.5 centimorgan and subjected to parametric linkage analysis. RESULTS: In the 10 affected family members, ARMD was manifest by the presence of large, soft, confluent drusen accompanied by varying degrees of retinal pigment epithelial degeneration and/or geographic atrophy. Age-related macular degeneration segregated as an autosomal-dominant trait, with the disease locus mapping to chromosome 1q25-q31 between markers D1S466 and D1S413, with a multipoint lod score of 3.00. CONCLUSION: Age-related macular degeneration localized to chromosome 1q25-q31 (gene symbol, ARMD1) as a dominant trait in a large family with a predominantly dry phenotype. CLINICAL RELEVANCE: Identification of ARMD genes will facilitate early diagnosis and aid in understanding the molecular pathophysiological mechanisms of ARMD. This knowledge will contribute to the development of preventive and improved treatment strategies.
Aged↗
Comparison of three treatment regimens of inhaled sodium cromoglycate in the management of adult patients with severe, steroid-dependent asthma.
BACKGROUND: Asthmatic patients whose asthma remains poorly controlled despite treatment with high doses of inhaled corticosteroids and co-administration of oral corticosteroids are a difficult problem in therapeutics. OBJECTIVE: To investigate the relative efficacy of three treatment regimens of inhaled sodium cromoglycate in the treatment of adult, severe, corticosteroid-dependent patients as determined by the reduction in the dose of oral corticosteroids and change in lung function. METHODS: Open, randomized, group comparative trial of 12 weeks duration in asthmatic patients attending a hospital outpatient department. Patients whose asthma is (1) severe according to the classification of the Japanese Society of Allergology, (2) stable, and (3) needing treatment with at least 1600 microg of inhaled beclomethasone dipropionate and 5 mg or greater of oral prednisolone per day. The three treatment regimens of inhaled sodium cromoglycate were group A received sodium cromoglycate powder at a dose of 16 mg/day administered by a metered dose inhaler. Group N received sodium cromoglycate aqueous solution at a dose of 80 mg/day administered by a nebulizer. Group C received sodium cromoglycate aqueous solution (80 mg/day) combined with salbutamol (3 mg/day) administered by a nebulizer. The main outcome measures were a change in the daily dose of oral corticosteroids and in lung function with twice daily measurements of peak expiratory flow (PEF) recorded in the morning (PEF AM) and in the evening (PEF PM). RESULTS: Mean reduction in oral corticosteroid dose/day was group A, 3.68 mg (95% CI 1.35,5.95); group N, 3.59 mg (95% CI 0.73,6.45); and group C, 3.97 mg (95% CI 1.81,6.13). The dosage reductions are all significant but with no differences between the groups. The mean increase in PEF over the last 4 weeks of treatment compared with baseline values was significant in all groups. The increases in group C are significantly greater than those in the other groups. These changes are all significant and the increases in group C are significantly greater than those in the other groups. CONCLUSIONS: Inhaled sodium cromoglycate may be a useful additional treatment in the management of adult patients with severe, oral steroid-dependent asthma. Of the three methods of administration compared in this trial the most useful immediate results were obtained when the drug was administered as an aqueous solution mixed with salbutamol and delivered by a powered nebulizer.
Administration, Inhalation↗
Communication about risk: diversity among primary care professionals.
OBJECTIVE: We aimed to identify the important clinical topics and to report current practice of communication about risk in primary care. METHODS: We carried out a qualitative study using six semi-structured focus group discussions with primary care professionals. The subjects were 36 primary care professionals from general practice, practice nurse, district nurse, community psychiatric nurse and health visitor disciplines. RESULTS: All clinical topics were felt to raise issues of effective risk communication. Participants expressed concern about the lack of accessible up-to-date information and the problems of conveying information to patients. They described the circumstances and contexts in which communication varies and is difficult, and identified media and medico-legal influences and professional uncertainty as also contributing to the problems of risk communication. Specific training in risk communication was identified as an important need. CONCLUSIONS: The complexity of risk communication and diversity of influences on it will require wide-ranging interventions in order to address them. Standardized communication may be a difficult goal to attain.
Communication↗
Communication about risk: the responses of primary care professionals to standardizing the 'language of risk' and communication tools.
OBJECTIVE: We aimed to gauge responses of primary care professionals to standardization of the 'language of risk' and risk communication tools. METHODS: We carried out a qualitative study using six semi-structured focus group discussions. The subjects were 36 primary care professionals from general practice, practice nurse, district nurse, community psychiatric nurse and health visitor disciplines. RESULTS: Between professionals, the standardization of the language of risk was felt to have potential benefit in making professionals consistent in their appreciation of risks and communication with each other. Between professionals and patients, standardized language was thought inappropriate or insufficient because of contextual variation in communication and interpretation of risk information by patients. The use of more-detailed comparisons of risks was felt to be a potentially effective development of risk communication in practice. CONCLUSIONS: A standard language of risk communication was perceived as being potentially helpful for communication between professionals, but many respondents were sceptical about its usefulness in communication with patients.
Communication↗
Mutations in the gene encoding starch synthase II profoundly alter amylopectin structure in pea embryos.
Mutations at the rug5 (rugosus5) locus have been used to elucidate the role of the major soluble isoform of starch synthase II (SSII) in amylopectin synthesis in the developing pea embryo. The SSII gene maps to the rug5 locus, and the gene in one of three rug5 mutant lines has been shown to carry a base pair substitution that introduces a stop codon into the open reading frame. All three mutant alleles cause a dramatic reduction or loss of the SSII protein. The mutations have pleiotropic effects on the activities of other isoforms of starch synthase but apparently not on those of other enzymes of starch synthesis. These mutations result in abnormal starch granule morphology and amylopectin structure. Amylopectin contains fewer chains of intermediate length (B2 and B3 chains) and more very short and very long chains than does amylopectin from wild-type embryos. The results suggest that SSII may play a specific role in the synthesis of B2 and B3 chains of amylopectin. The extent to which these findings can be extrapolated to other species is discussed.
Amylopectin↗
A multiunit model of solute and water removal by inner medullary vasa recta.
A recent model of volume and solute microcirculatory exchange in the renal medulla based on a single descending vasa rectum (DVR) was extended to account for the varying number of vessels along the corticomedullary axis. The assumption that concentration polarization at the walls of ascending vasa recta (AVR) during volume uptake eliminates transmural oncotic pressure gradients was examined. In this limiting case, small hydrostatic pressure gradients can drive AVR volume uptake if the pressure in the interstitium exceeds that in the AVR lumen. The calculated hydraulic pressure difference across AVR yielding agreement between predicted and measured values of AVR-to-DVR blood flow rate ratios was found to be smaller than the reported maximum pressure difference AVR can sustain. Simulations also confirmed previous conclusions suggesting that the presence of urea transporters in DVR counterbalances that of water channels that would otherwise decrease the efficiency of small solute trapping in the renal medulla.
Capillaries↗
Research and the Goal of Improving Patient Care.
The goal of this article is to raise issues associated with the underlying assumptions of our research approaches and the nature of health/disease in conventional medical care and complementary and alternative medical care. Different types of efficacy are discussed in terms of randomized controlled trials and outcomes research. The demands of different audiences for research results suggest that researchers need to carefully specify the research question in the context of the state-of-the-knowledge. Appropriate matching of the study design, the nature of the disease, the nature of the treatment and what is known is essential to designing and implementing research that actually could improve patient care.
Journal Article↗
Carbon dioxide embolism following diagnostic hysteroscopy.
A 50-year-old woman ASA 2 underwent carbon dioxide hysteroscopy under general anaesthesia. Monitoring showed a sudden and rapid fall in end-tidal carbon dioxide followed by oxygen desaturation. She became pulseless and cyanosed. Resuscitation with oxygen, intravenous adrenaline and head-down tilt restored her to haemodynamic stability. Hyperbaric therapy was also administered as air embolism could not be excluded.
Anesthesia, General↗