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Biomedical subjects

J Richardson

Publications and source records attributed to J Richardson.

At least 37 records · Page 2Linked to original sources

Communication skills training in postgraduate medicine: the development of a new course.

It has long been accepted that communication is of central importance in healthcare, and a core aspect of clinical competence. Many educational institutions and Royal Colleges now reflect this and consider communication skills a priority in postgraduate examination. The new examination "Practical Assessment of Clinical and Examination Skills" has replaced the Royal College of Physicians MRCP part 2 clinical and oral examination. This examination now consists of five clinical stations, two of which focus on communication skills. A short course for postgraduate trainees has been designed to address the communication skills requirements of the part 2 clinical examination. The aims, development, and content of the course are described. Emphasis is placed on candidates practising skills with patients and receiving feedback during the course. Evidence suggests that practice with feedback is an essential ingredient of communication skills courses, and is more effective than other methods such as observing experts or video examples, or simply discussing issues in communication. Results of a preliminary evaluation indicate that the course was perceived as valuable by candidates and that the aims, format, and content were appropriate. Although the preliminary evaluation was largely positive, it could be argued that the acid test of the effectiveness of a course is an objective evaluation of skills, observed before and after the course, a development that is being considered for future evaluation of the course. Recommendations for applying this type of training to postgraduate trainees in any branch of medicine are given.

Clinical Competence↗

A population-based study of primary care predictors of non-attendance for cervical screening.

OBJECTIVE: To identify and estimate the population impact of primary care service delivery factors that independently predict non-attendance for cervical screening. SETTING: Screening records of all eligible women aged 30 years and over and resident in the former Manchester Health Authority area were analysed (n=72,613). METHODS: Practice-level and GP-level explanatory variables, along with area-level covariates, were obtained and merged to the study data set. Logistic regression models were used to identify factors associated with having no recorded history of attending NHS cervical screening services. A multivariate model was created to identify independent predictors of non-attendance with comprehensive adjustment for women's age, area-level socio-demographic factors, and other primary care factors. Attributable fraction estimates were used to assess the population impact of the independent predictors. RESULTS: Large practice size (>4,000 patients), single-handed practice, South Asian male GP, part-time GP employment status, older age and birthplace overseas, and area-level measures of deprivation and transience independently predicted non-attendance. Women born overseas and registered at larger practices were especially unlikely to have ever attended. The combined population attributable fraction estimate for the independent predictors reflecting primary care service delivery was almost 40%, and that for all variables in the final model was over 70%. CONCLUSIONS: Independent predictors of non-attendance reflecting general practice structure, workload and GP characteristics were identified. Although relative risks were modest, the collective population impact of these factors was considerable, which has implications for the implementation of informed targeting and the development of new screening services by Primary Care Trusts.

Adult↗

Mutant presenilin 1 proteins induce cell death and reduce tau-dependent processes outgrowth.

The expression of familial Alzheimer's disease mutants of presenilin-1 (PS1) proteins has been observed to induce cell death in cellular systems. To investigate how this phenomenon might be associated to alterations of the microtubule network, we have studied the effect of wild-type and mutant (C263R, P264L and delta9) PS1 proteins expression on the formation of microtubule-dependent processes outgrowth and the association of PS1 to the insoluble cytoskeletal fraction in a cell line expressing the tau microtubule-associated protein. Expression of wild-type and mutant PS1 was associated with increased cell death, most marked for the P264L and delta9 mutants. The three PS1 mutants induced a significant reduction of the length of cell processes. These effects were not associated to a change in tau phosphorylation. However, the mutant PS1 proteins increased the proportion of insoluble tau in the cytoskeletal fraction and they were concentrated in the same fraction. These results suggest that PS1 proteins interact with the microtubule network, affect its organization and that this phenomenon, more marked for the PS1 mutants, might play a role in the cell dysfunction induced by mutant PS1 proteins.

Animals↗

Factors affecting the spread of bupivacaine in the adult thoracic paravertebral space.

Factors affecting the spread of bupivacaine in the paravertebral space were investigated in patients undergoing paravertebral nerve blocks for the treatment of chronically painful conditions. Injections of bupivacaine 0.5%, 10-15 ml mixed with depomedrone up to 80 mg were repeated at 2-wk intervals up to a maximum of four times. A blinded observer mapped out the subsequent distribution of sensory loss to cold on both sides of the torso at 5-min intervals after each injection. Age, sex, height and weight did not correlate with the block; nor did injectate volume, mass of bupivacaine, previous posterolateral thoractomy and spread of radiocontrast. Injections repeated at 2-wk intervals in the same patient resulted in different degrees of spread that were unrelated to one another. Time to peak onset of blockade was 40 min in 95% of patients. A single bolus of bupivacaine produces a safe but unpredictable block. Yet to be defined physical properties and anatomical factors are probably key determinants of the spread of bupivacaine in the paravertebral space. This single bolus technique may be better supplanted by a reversion to the older multiple level injection technique.

Adult↗

Dissatisfaction with medical care among women with HIV: dimensions and associated factors.

Studies have shown that women with HIV/AIDS in the USA are less likely than men to have access to appropriate health care and to utilize services, including the latest antiretroviral drug therapies. One explanation for this underutilization is patient dissatisfaction with medical care. Dissatisfaction with care has been shown to be associated not only with treatment underutilization, but also with discontinuity of care and poor clinical outcomes. Using Patient Satisfaction Questionnaire data from a national cohort of women with HIV, this study examines levels of dissatisfaction across seven established dimensions of care, and uses multivariate analysis to identify patient characteristics associated with these dimensions (N = 1,303). Women were most dissatisfied with access to care and the technical quality of care, and least dissatisfied with financial aspects of care and their providers' interpersonal manner. Women who reported poor health, who had depressive symptomatology, who were not receiving antiretroviral therapy (ART), who had no consistent care providers or who were Hispanic/Latina were more likely to be dissatisfied across most dimensions of care. Implications for enhancing clinical care for women with HIV/AIDS and overcoming barriers to utilization of care and treatment are discussed.

Acquired Immunodeficiency Syndrome↗

Health authority cervical screening recall policies and time since last smear: a retrospective cohort analysis in the north west England.

OBJECTIVES: To evaluate the impact of health authority cervical screening programmes upon the the actual screening interval for women attending as a result of routine recall and to assess the impact of general practice recall policies on attendance for smears. SETTING: Nine health authorities constituting the Lancashire and Greater Manchester zones of the North West region on the National Health Service. METHODS: Information was obtained on the invitation and recall policies of each health authority. A retrospective analysis of information held on cervical screening databases ("Exeter" computer systems was performed. The proportions of smears, classified by a screening interval of "unscheduled", "on-time" or "overdue", in the different health authority recall programmes were compared. General practices in one health authority (operating five-yearly recall) were contacted to determine their current practice screening policy. RESULTS: Women who were invited as part of a three-yearly recall programme were more likely to attend for smears at intervals of 3-5 years than those on a five-yearly recall programme (68% vs 47%). Those health authorities operating three-yearly recall that issued recall invitations to women more than four weeks before the date the smear was due had higher rates of "unscheduled" smears. In the one health authority (operating a five-yearly recall programme) in which we determined general practice screening policy, 62% of the general practitioners (GPs) were operating their own three-yearly recall policy; these GPs had a higher proportion of the women who attended for smears "on-time" (51%) than did those who relied on the health authority five-yearly recall procedure (44%). CONCLUSIONS: Despite the cervical screening programme being a national programme, there is scope at a local level for considerable variation in the interpretation of national guidance. This variation effects the extent to which programmes comply with the requirement to screen all women at an interval of 3-5 years.

Adult↗

Bronchoscopic lung volume reduction.

AIM: Because traditional lung volume reduction involves major surgery in unfit patients, resource implications are formidable. Many patients are too ill for consideration and overall survival rates have lead to questions about its continuation. We report on a new method of lung volume reduction, through a bronchoscopic approach. Patients with severe dyspnoea with end stage emphysema were recruited. Target areas for collapse therapy were upper lobes or segments with severe destruction, occupying a large volume, with surrounding lung compression and little perfusion. These were delineated radiologically and with ventilation-perfusion scanning. Endobronchial bloc-kade was initially with detachable, silicone balloons and later with especially designed and hospital manufactured stainless steel wire stents containing bio-compatible sponge. METHODS: Five males and 3 females with preoperative breathlessness at rest and muscle wasting were treated. Operative time was a mean of 67.5 min. Rehabilitation began immediately and 7 patients left hospital the following day. RESULTS: Five patients had improvements in well-being, dyspnoea, exercise tolerance, lifestyles and medication requirements. One patient survived at least 2 years and 2 are still alive 4(1/2) years later. Endoscopic balloon replacement with wire and sponge devices was required in 5 patients. Complications were related to intraoperative oxygenation problems in 2 patients and late infections in 4. CONCLUSIONS: Bronchoscopic lung volume reduction for the treatment of end-stage emphysema subjectively improved the majority of patients. The use of stents was promising: balloons were disappointing.

Aged↗

Diversity of Burkholderia isolates from woodland rhizosphere environments.

AIMS: Determination of genetic diversity among UK Burkholderia cepacia isolates from various environmental niches, principally woodland tree rhizospheres and onions. METHODS AND RESULTS: Genus determination was made using polymerase chain reaction (PCR) amplification and fatty acid methyl ester profiling. Genetic diversity was investigated by repetitive sequence genetic PCR fingerprinting. Several onion isolates were similar to clinical isolates but others were diverse. Some environmental isolates were possibly synonymous with B. cepacia and B. gladioli but most from woodland rhizospheres were distinct and clustered together. The 16S rRNA genes of representatives from these clusters were PCR amplified, sequenced and phylogenetically compared with all known Burkholderia and related species. This revealed that the rhizospheric isolates had closest affinity with Burkholderia spp. with known bioremediative and biocontrol capabilities and were unrelated to taxa comprising plant or human pathogenic strains. CONCLUSIONS: All of the analyses investigated revealed that environmental and onion isolates of B. cepacia complex bacteria are genetically diverse but that woodland rhizospheric isolates are related to each other and unrelated to plant or human pathogenic strains. SIGNIFICANCE AND IMPACT OF THE STUDY: Woodland rhizospheric isolates of B. cepacia are potentially good candidates for use in bioremediation and biocontrol, as they appear distinct from plant or human pathogenic strains.

Burkholderia↗

Community coronary units: strategies to promote pre-hospital thrombolysis.

Early diagnosis and the early delivery of pre-hospital thrombolysis in cases of acute myocardial infarction (AMI) have been shown to decrease mortality. Despite strong evidence of its benefits, pre-hospital thrombolysis rates are still worryingly low. The challenge is to empower community practitioners to deliver thrombolysis. In the Grampian region there is a network of community hospitals which have been equipped with both videoconferencing and remote telemetry equipment. This allows realtime consultation with the local accident and emergency department and coronary care unit. Early trials of the system show that clinical information can be viewed in realtime, with transfer of a 12-lead electrocardiogram at 60 s intervals. This will give general practitioners unprecedented access to specialist advice. Our aim is to use a combination of teaching and decision support technology to ensure that all patients with AMI have the opportunity to access timely and appropriate prehospital thrombolysis.

Acute Disease↗

Changes in physical functioning in institutionalized older adults.

PURPOSE: Chronic care and long-term care facilities have a responsibility to provide care that enables residents to attain or maintain their maximal functional capacity. This paper uses the Minimum Data Set (MDS) to examine changes in functional health. METHODS: One hundred and thirty-eight residents were assessed quarterly using the MDS over a 12 month period in a chronic care and long-term care institution. Physical functioning was conceptualized in two areas of physical limitations (e.g. bed mobility) and disability (e.g. dressing). RESULTS: Ten percent of the residents physical functioning improved. Gender, range of motion score at baseline, change in bed mobility and change in short term memory were strong independent predictors of changes in functional activity FL adjusted R2 = 0.23, F(5156) = 10.47, p<0.0001. The strongest independent predictors of change in ADL were gender, balance while standing at baseline, joint range of motion at baseline and change in depression scores, and weight loss, adjusted R2 = 0.24 , F(4157)= 13.38, p < 0.0001. CONCLUSIONS: Most residents' physical functioning showed a deterioration or remained stable. Impairments which best explained changes in functioning such as range of motion or balance in standing are modifiable and should be targeted in interventions by nursing and rehabilitation staff.

Activities of Daily Living↗

Relation between childhood sexual and physical abuse and risk of revictimisation in women: a cross-sectional survey.

BACKGROUND: Women who are physically and sexually abused in childhood are at increased risk of victimisation in adulthood. Research has concentrated on sexual revictimisation, and has not included investigation of other abusive experiences, nor examination of prevalence and effects of abuse on adult revictimisation. We aimed to examine the relation between childhood trauma and adult revictimisation, and identify confounding factors. METHODS: We did a cross-sectional survey of 2592 women who were attending primary care practices in east London, UK, with self-administered anonymous questionnaires. We included questions on physical and sexual abuse in childhood; on domestic violence, rape, indecent assault, and other traumatic experiences in adulthood; and on alcohol and other drug abuse. We analysed associations between childhood and adulthood abuse with multiple logistic regression. FINDINGS: 1207 (55%) of 2192 eligible women were recruited and completed the questionnaire. Abusive experiences co-occurred in both childhood and adulthood. Repetition and severity of childhood abuse were independently associated with specific types of adult revictimisation. Unwanted sexual intercourse (<16 years) was associated with domestic violence in adulthood (odds ratio 3.54; 95% CI 1.52-8.25) and with rape (2.84; 1.09-7.35); and severe beatings by parents or carers with domestic violence (3.58; 2.06-6.20), rape (2.70; 1.27-5.74), and other trauma (3.85; 2.23-6.63). INTERPRETATION: Childhood abuse substantially increases risk of revictimisation in adulthood. Women who have experienced multiple childhood abuse are at most risk of adult revictimisation. Identification of women who have undergone childhood abuse is a prerequisite for prevention of further abuse.

Adolescent↗

Dishevelled regulates the metabolism of amyloid precursor protein via protein kinase C/mitogen-activated protein kinase and c-Jun terminal kinase.

Alzheimer's disease (AD) is a disorder of two pathologies: amyloid plaques, the core of which is a peptide derived from the amyloid precursor protein (APP), and neurofibrillary tangles composed of highly phosphorylated tau. Protein kinase C (PKC) is known to increase non-amyloidogenic alpha-secretase cleavage of APP, producing secreted APP (sAPPalpha), and glycogen synthase kinase (GSK)-3beta is known to increase tau phosphorylation. Both PKC and GSK-3beta are components of the wnt signaling cascade. Here we demonstrate that overexpression of another member of this pathway, dishevelled (dvl-1), increases sAPPalpha production. The dishevelled action on APP is mediated via both c-jun terminal kinase (JNK) and protein kinase C (PKC)/mitogen-activated protein (MAP) kinase but not via p38 MAP kinase. These data position dvl-1 upstream of both PKC and JNK, thereby explaining the previously observed dual signaling action of dvl-1. Furthermore, we show that human dvl-1 and wnt-1 also reduce the phosphorylation of tau by GSK-3beta. Therefore, both APP metabolism and tau phosphorylation are potentially linked through wnt signaling.

Adaptor Proteins, Signal Transducing↗

Activated MEK5 induces serial assembly of sarcomeres and eccentric cardiac hypertrophy.

Mitogen-activated protein kinase (MAPK) pathways couple intrinsic and extrinsic signals to hypertrophic growth of cardiomyocytes. The MAPK kinase MEK5 activates the MAPK ERK5. To investigate the potential involvement of MEK5-ERK5 in cardiac hypertrophy, we expressed constitutively active and dominant-negative forms of MEK5 in cardiomyocytes in vitro. MEK5 induced a form of hypertrophy in which cardiomyocytes acquired an elongated morphology and sarcomeres were assembled in a serial manner. The cytokine leukemia inhibitory factor (LIF), which stimulates MEK5 activity, evoked a similar response. Moreover, a dominant-negative MEK5 mutant specifically blocked LIF-induced elongation of cardiomyocytes and reduced expression of fetal cardiac genes without blocking other aspects of LIF-induced hypertrophy. Consistent with the ability of MEK5 to induce serial assembly of sarcomeres in vitro, cardiac-specific expression of activated MEK5 in transgenic mice resulted in eccentric cardiac hypertrophy that progressed to dilated cardiomyopathy and sudden death. These findings reveal a specific role for MEK5-ERK5 in the induction of eccentric cardiac hypertrophy and in transduction of cytokine signals that regulate serial sarcomere assembly.

Animals↗

Entorhinal cortex atrophy in epilepsy patients exhibiting normal hippocampal volumes.

OBJECTIVE: To determine whether MRI volumetric measurement of the entorhinal cortex could detect structural damage and lateralize the seizure focus in patients with temporal lobe epilepsy in whom no measurable hippocampal abnormalities were found. BACKGROUND: A reduction in the volume of the entorhinal cortex ipsilateral to the seizure focus in patients with intractable temporal lobe epilepsy and hippocampal atrophy was recently shown. METHODS: MRI volumetric analysis of the entorhinal cortex was performed using a T1-weighted three-dimensional gradient echo sequence in 24 control subjects and 22 patients with temporal lobe epilepsy and normal hippocampal volumes. Thirteen patients underwent surgery, with a mean postoperative follow-up of 36 months. RESULTS: Group analysis (multivariate analysis of variance) showed a reduction in the volume of the entorhinal cortex ipsilateral to the seizure focus in patients with left (p < 0.0001) and right temporal lobe epilepsy (p < 0.0001). Lateralization of the seizure focus could be done in 14 of 22 patients (64%) based on entorhinal cortex volumetry. CONCLUSION: Entorhinal cortex atrophy ipsilateral to the seizure focus supports the presence of structural damage in the mesial temporal lobe in patients with temporal lobe epilepsy and normal hippocampal volumes and emphasizes the participation of the entorhinal cortex in the pathogenesis of this disorder.

Adult↗

A degradation signal located in the C-terminus of p21WAF1/CIP1 is a binding site for the C8 alpha-subunit of the 20S proteasome.

The cyclin-dependent kinase inhibitor p21WAF1/CIP1 is a key regulator of cell-cycle progression and its expression is tightly regulated at the level of transcription and by proteasome-dependent proteolysis. The turnover of p21WAF1/CIP1 by proteasomes does not always require the ubiquitylation of p21WAF1/CIP1 suggesting that there could be an alternative pathway into the proteasome. Here we show that the C8 alpha-subunit of the 20S proteasome interacts with the C-terminus of p21WAF1/CIP1 and mediates the degradation of p21WAF1/CIP1. A small deletion in this region that disrupts binding to C8 increased the half-life of p21WAF1/CIP1 expressed in vivo. In contrast a deletion that increased the affinity between C8 and p21WAF1/CIP1 significantly reduced the stability of the latter. These data suggest that interaction with a 20S proteasome alpha-subunit is a critical determinant of p21WAF1/CIP1 turn-over and show how non-ubiquitylated molecules might bypass the 19S regulator of the proteasome and become targeted directly to the 20S, core protease. Consistent with this, p21WAF1/CIP1 was degraded rapidly by purified 20S proteasomes in a manner that was dependent on the C8-interaction domain.

3T3 Cells↗

Natural antisense transcripts are detected in different cell lines and tissues of cats infected with feline immunodeficiency virus.

Feline immunodeficiency virus (FIV) is a lentivirus inducing an AIDS-like disease in cats, thus providing an interesting model for AIDS study. FIV and HIV-1 possess a similar genomic arrangement of structural and non-structural genes, whose expression is regulated by related genetic mechanisms. On the DNA strand complementary to the HIV-1 envelope messenger, an open reading frame (ORF) has been identified which encompasses the Rev Responsive Element (RRE), a cis-acting element critical to HIV gene expression. This ORF was highly conserved among HIV-1 isolates and had the potential to encode a hydrophobic protein. A corresponding antisense transcript was detected in cells infected with HIV-1, and appeared to encode an antisense protein. In the present study, we have identified a well-conserved antisense ORF, also coincident with the RRE region, in the genome of 21 FIV isolates. The predicted protein, 103 amino acids in length, is highly hydrophobic, as is the case for that of HIV-1. In addition, we have shown that a corresponding transcript, complementary to the transmembrane sequence of the FIV envelope gene, was produced in different cellular and viral contexts, that is, ex vivo and in vivo in FIV infected cell lines and tissues of infected cats, respectively. Expression of antisense transcripts might therefore be of general importance in the natural history of retroviruses.

Amino Acid Sequence↗

Incidence of the cblA major subunit pilin gene amongst Burkholderia species.

PCR-amplification has been used to screen 75 isolates of the Burkholderia cepacia complex for the cblA pilin gene. PCR-amplified products of the correct size (664 bp) were cloned and sequenced and the sequences compared. Apart from in the control, epidemic cystic fibrosis (CF)-associated B. cepacia lineage we also identified, for the first time, cblA genes in a unique, non-CF clinical isolate from France and a plant (onion) pathogenic isolate from Italy. The sequence of the cblA gene amplified from the clinical isolate was more diverged from the epidemic lineage than that amplified from the onion pathogenic isolate.

Amino Acid Sequence↗