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Biomedical subjects

J Walker

Publications and source records attributed to J Walker.

At least 19 recordsLinked to original sources
PubMed2006

Duplex ultrasound scanning is reliable in the detection of endoleak following endovascular aneurysm repair.

OBJECTIVE: To investigate the value of duplex ultrasound scanning (DUSS) in the routine follow up of patients following EVAR. METHODS: Imaging was reviewed for 310 consecutive patients undergoing EVAR at a single centre. Concurrent ultrasound and CT scans were defined as having occurred within 6 months of each other. There were 244 paired concurrent DUSS and CT scans which were used for further analysis. These modalities were compared with respect to sensitivity, specificity, positive and negative predictive values and level of agreement (by Kappa statistics) using CT as the 'gold standard'. RESULTS: DUSS failed to detect a number of endoleaks which were seen on CT and the sensitivity of this test was therefore poor (67%). However, the specificity of DUSS compared more favourably with a value of 91%. Positive predictive values ranged from 33-100% but negative predictive values were more reliable with values of 91-100% at all time points post operatively. There were no type I leaks, or endoleaks requiring intervention which were missed on DUSS. Overall, there was a 'fair' level of agreement between the two imaging modalities using Kappa statistics. CONCLUSION: Although DUSS is not as sensitive as CT scanning in the detection of endoleak, no leaks requiring intervention were missed on DUSS in this study. DUSS is much cheaper than CT and avoids high doses of radiation. DUSS therefore remains a valuable method of follow up after EVAR and can reduce the need for repeated CT scans.

Aneurysm↗
PubMed2006

WATCH IT: a community based programme for obese children and adolescents.

BACKGROUND: The WATCH IT programme was developed to address the needs of obese children from disadvantaged communities in Leeds and has been running since January 2004. Results of the pilot phase, prior to a randomised controlled trial, are presented. METHODS: A process evaluation to assess success of implementation was conducted in December 2004. User views (parent and child) were obtained by semi-structured interviews and focus groups. Change in BMI SD score was calculated for children attending between January 2004 and November 2005. RESULTS: A total of 94 children (49 girls, 45 boys), mean age (SD) 12.2 (2.0) years attended. They were moderately to severely obese (mean BMI SDS 3.09 (0.45), with low quality of life and self-image scores. There was a significant reduction in overweight at 6 months (DeltaBMI SD -0.07), especially for teenagers (DeltaBMI SD -0.13) and girls (DeltaBMI SD -0.07). The programme was successfully implemented. By December 2004 mean attendance was 2.1 (0.7) clinics per month, and sports sessions 3.3 (1.7) sessions per month. Fourteen children dropped out and non-attendance was low (only 7.5% sessions missed in 12 months). Qualitative research indicated significant appreciation of the service, with reported increase in self-confidence and friendships, and reduction in self-harm. CONCLUSION: WATCH IT offers a model for a community based service for obese children. The programme suggests that effective care can be delivered by health trainers supervised by health professionals, and so potentially provides a cost effective programme within children's communities. These findings are encouraging, and need to be substantiated by extension to other locations and evaluation by randomised controlled trial.

Adolescent↗
PubMed2006

Ultrasound based measurement of 'carotid stenosis >70%': an audit of UK practice.

OBJECTIVES: To determine velocity thresholds for diagnosing 'carotid stenosis >70%' and whether Vascular Studies Units in the United Kingdom used ECST or NASCET measurement methods. DESIGN: Questionnaire to 102 members of the Society of Vascular Technology of Great Britain and Ireland. RESULTS: One quarter (26%) of respondents reported that their unit used the NASCET measurement method, 31% used the ECST method, while 43% did not know. When all velocity criteria were pooled and compared, an almost equal proportion of ECST, NASCET and 'do not know' respondents used a peak systolic velocity threshold of >230 cm/s as being diagnostic of a 'stenosis >70%'. Interestingly, this velocity is now the threshold proposed by a North American consensus group for diagnosing a NASCET stenosis of >70%. CONCLUSIONS: This audit suggests that there is considerable confusion about what constitutes an ultrasound based diagnosis of 'stenosis >70% in the United Kingdom.

Blood Flow Velocity↗
PubMed2006

Sensitization to king scallop (Pectin maximus) and queen scallop (Chlamys opercularis) proteins.

OBJECTIVE: To report a case of occupational asthma and urticaria due to the queen scallop (Chlamys opercularis) and king scallop (Pectin maximus). BACKGROUND: A 40-year-old female worked in a shellfish-processing plant, handling king and queen scallops for 5 years. At the time of investigation, she described a 2-year history of work-related respiratory symptoms. METHODS: Serial peak expiratory flow rate readings were recorded and an OASYS study completed. A workplace visit was undertaken and specific immunoglobulin (IgE) radioallergosorbent (RAST) testing of scallop extracts was performed. RESULTS: The OASYS study was consistent with occupational asthma. RAST testing demonstrated evidence of specific sensitization (IgE) to queen and king scallop. There was also some cross-reactivity observed with other shellfish (prawns and crabs). CONCLUSION: Workers exposed to aerosols from scallop species are at risk of occupational asthma and require effective respiratory health surveillance.

Adult↗
PubMed2006

Quantifying the functional rehabilitation of injured football players.

OBJECTIVE: To determine whether quantified, auditable records of functional rehabilitation can be generated using subjective assessments of players' performance in fitness tests routinely used in professional football. METHOD: Ten sequential test elements grouped into three phases (fitness, ball and match skills, match pace football) were used to monitor players' functional recovery from injury. Physiotherapists subjectively assessed players' performance in each test element using a six point subjective rating scale. Satisfactory performance in each element of the assessment programme added 10% to the injured player's recovery score. Daily recovery scores for injured players were recorded against the time spent in functional rehabilitation. RESULTS: Rehabilitation data for 118 injuries sustained by 55 players over two seasons were recorded. The average time in functional rehabilitation depended on the time spent in pre-functional rehabilitation and the nature and location of injury. Benchmark functional rehabilitation curves (y = mln(x) + c) were developed for thigh (n = 15) and lower leg (n = 8) muscle strains and knee (n = 7) and ankle (n = 9) ligament sprains (R(2) = 0.95-0.98). CONCLUSIONS: A structured, quantified rehabilitation programme based on routine fitness and skills exercises and a graded subjective assessment of performance provides an auditable record of a player's functional recovery from a range of lower limb injuries and a transparent exit point from rehabilitation. The proposed method provides a permanent record of the functional rehabilitation of players' injuries and evidence based data to support management's return to play decisions.

Adult↗
PubMed2005

Developing a standard short questionnaire for the assessment of patient satisfaction with out-of-hours primary care.

BACKGROUND: Governmental reviews of out-of-hours services in England and Scotland have recommended that a standard questionnaire should be used to assess patient satisfaction. This is important because of the rapid introduction of new forms of care. OBJECTIVE: To produce a brief, reliable and valid measure of patient satisfaction for use by a wide variety of providers of out-of-hours primary care. METHODS: The Short Questionnaire for Out-of-Hours care was designed and compared with a longer questionnaire which had been validated and used in earlier research. Questionnaires were sent to 1906 people contacting an out-of-hours GP co-operative. Three versions of the short questionnaire were used with different formats. Analysis compared the response rates, measurement properties, concurrent and construct validity of the short and long questionnaires, and of different versions of the short questionnaire. RESULTS AND CONCLUSIONS: There was no significant difference in the overall response rates obtained from the short or long questionnaires (45.7% versus 41.9%; P = 0.17). The effective response rate of questionnaires from which all satisfaction scales could be calculated was higher for the short questionnaire (43.0% versus 36.4%; P = 0.01). There were no significant differences in response rates or distribution of responses between different versions of the short questionnaire. There was moderate agreement between items on the short questionnaire and corresponding scales on the long questionnaire. Scores using the short questionnaire showed anticipated relationships with the age and sex of patients and with characteristics of how the service was delivered. The SQOC is valid and reliable for routine service use.

After-Hours Care↗
PubMed2005

Protective immunogenicity of the paraflagellar rod protein 2 of Leishmania mexicana.

Paraflagellar rod proteins (PFR) are a potent immunogen against experimental Trypanosoma cruzi infection. PFR are highly conserved among kinetoplastid parasites. We therefore evaluated the immunogenicity of the Leishmania mexicana pfr-2 gene and protein product in the hamster model of American cutaneous leishmaniasis. Immunization with pfr-2 DNA-induced specific antibody, confirming immunogenicity. Subsequent challenge with 10,000 and 500 stationary phase L. mexicana promastigotes respectively, resulted in delayed appearance of lesions, and significant reduction in lesions post infection in male hamsters, yet exacerbated lesions in female hamsters. Immunization with recombinant PFR-2 protein (rPFR-2) prevented lesion development in female hamsters challenged with L. panamensis, but was ineffective against L. mexicana. Nevertheless, prime boost immunization of female hamsters with rPFR and pfr-2 DNA significantly reduced lesion size following challenge with 500 L. mexicana promastigotes, supporting the relevance of PFR-2 as a potential vaccine constituent.

Animals↗
PubMed2005

Bladder and sexual function following resection for rectal cancer in a randomized clinical trial of laparoscopic versus open technique.

BACKGROUND: Bladder and sexual dysfunction are recognized complications of mesorectal resection. Their incidence following laparoscopic surgery is unknown. METHODS: Bladder and sexual function were assessed in patients who had undergone laparoscopic rectal, open rectal or laparoscopic colonic resection as part of the UK Medical Research Council Conventional versus Laparoscopic-Assisted Surgery In Colorectal Cancer (CLASICC) trial, using the International Prostatic Symptom Score, the International Index of Erectile Function and the Female Sexual Function Index. Sexual and bladder function data from the European Organization for Research and Treatment of Cancer QLQ-CR38 collected in the CLASICC trial were used for comparison. RESULTS: Two hundred and forty-seven (71.2 per cent) of 347 patients completed questionnaires. Bladder function was similar after laparoscopic and open rectal operations for rectal cancer. Overall sexual function and erectile function tended to be worse in men after laparoscopic rectal surgery than after open rectal surgery (overall function: difference - 11.18 (95 per cent confidence interval (c.i.) -22.99 to 0.63), P = 0.063; erectile function: difference -5.84 (95 per cent c.i. -10.94 to -0.74), P = 0.068). Total mesorectal excision (TME) was more commonly performed in the laparoscopic rectal group than in the open rectal group. TME (odds ratio (OR) 6.38, P = 0.054) and conversion to open operation (OR 2.86, P = 0.041) were independent predictors of postoperative male sexual dysfunction. No differences were detected in female sexual function. CONCLUSION: Laparoscopic rectal resection did not adversely affect bladder function, but there was a trend towards worse male sexual function. This may be explained by the higher rate of TME in the laparoscopic rectal resection group.

Aged↗
PubMed2005

Comparison of the novel quantitative ARMS assay and an enriched PCR-ASO assay for K-ras mutations with conventional cytology on endobiliary brush cytology from 312 consecutive extrahepatic biliary stenoses.

BACKGROUND: Extrahepatic biliary stenosis (EBS) has malignant and benign causes. Patients with EBS are at risk of having or developing malignancy. Accurate diagnostic tests for early detection and surveillance are needed. The sensitivity of biliary cytology for malignancy is low. K-ras mutation analysis on brush cytology is a valuable adjunct, but specificity is low. A quantitative test for K-ras mutations has been developed: the amplification refractory mutation system (ARMS). AIM: To assess the test characteristics and additional value of ARMS in diagnosing the cause of EBS. METHODS: Brush samples from endoscopic retrograde cholangiopancreatography were collected from 312 patients with EBS. K-ras mutation analysis was performed using ARMS-allele specific amplification was coupled with real time fluorescent detection of PCR products. Results were compared with conventional cytology and K-ras mutation analysis using allele specific oligonucleotide (ASO) hybridisation, and evaluated in view of the final diagnosis. RESULTS: The test characteristics of ARMS and ASO largely agreed. Sensitivity for detecting malignancy was 49% and 42%, specificity 93% and 88%, and positive predictive value (PPV) 96% and 91%, respectively. The sensitivity of ARMS and cytology combined was 71%, and PPV was 93%. The specificity of ARMS could be increased to 100% by setting limits for the false positives, but reduced sensitivity from 49% to 43%. CONCLUSIONS: ARMS can be considered supplementary to conventional cytology, and comparable to ASO in diagnosing malignant EBS. A specificity of 100% can be achieved with ARMS, which should be considered in the surveillance of patients at risk for pancreatic cancer.

Adult↗
PubMed2004

Inhibition of P-glycoprotein function by XR9576 in a solid tumour model can restore anticancer drug efficacy.

Resistance to cancer chemotherapy involves both altered drug activity at the designated target and modified intra-tumour pharmacokinetic properties (e.g. uptake, metabolism). The membrane transporter P-glycoprotein (P-gp) plays a major role in pharmacokinetic resistance by preventing sufficient intracellular accumulation of several anticancer agents. Whilst inhibiting P-gp has great potential to restore chemotherapeutic effectiveness in blood-borne cancers, the situation in solid tumours is less clear. Therefore, the degree of resistance tumours pose to the cytotoxicity of vinblastine and doxorubicin was characterised using the multicellular tumour spheroid model. Tumour spheroids were generated from either drug-sensitive MCF7(WT) breast cancer cells or a resistant P-gp-expressing variant (NCI/ADR(Res)). Drug-induced cytotoxicity in tumour spheroids was measured using an outgrowth assay and compared with that observed in monolayer cultures. As anticipated, the 3-D organisation of MCF7(WT) in tumour spheroids was associated with a reduction in the potency of doxorubicin and vinblastine-i.e. the inherent multicellular resistance phenomenon. In contrast, tumour spheroids from NCI/ADR(Res) cells did not display multicellular resistance. However their constitutive expression of P-gp reduced the potency of both anticancer drugs. Moreover, the highly potent P-gp inhibitor, the anthranilic acid derivative, XR9576, was able to restore the cytotoxic efficacy of both drugs in tumour spheroids comprising NCI/ADR(Res) cells. The results suggest that inhibition of P-gp in solid tumours is achievable and that generation of potent inhibitors will provide a significant benefit towards restoration of chemotherapy in solid tissues.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2004

Understanding the social context of violent and aggressive incidents on an inpatient unit.

The English National Service Framework for Mental Health stipulates that the highest quality of health care should be provided for mental health service users. Incidents of aggression and violence militate against achieving that goal, yet such incidents are frequently reported in inpatient settings. Much research in this area reflects a dualistic, perpetrator/victim conceptualization of incidents. This study aimed to take a more systemic approach by treating violent and aggressive incidents as social interactions and by seeking to understand the social contexts in which they took place. In this paper we describe and discuss the main themes to emerge from 15 staff accounts of 11 incidents on one ward. A striking theme reflected throughout the interview data was the lack of staff engagement with clients, and particularly an inability to look at the world through clients' eyes in interpreting their behaviour. We conclude that the 'zero tolerance' campaigns currently being conducted in the UK in relation to aggression towards NHS staff are unlikely to succeed without attention to understanding why aggressive behaviour arises and identifying features of the caring environment that may contribute to it. Rather than adopting a position of 'zero tolerance', we argue that three steps are required following an aggressive incident: emotional support; critical reflection and learning; and the pursuit of accountability.

Aggression↗
PubMed2004

Rising obesity and expanding waistlines in schoolchildren: a cohort study.

A cohort of schoolchildren was followed up over 6 years from 1996 to 2001. In the final year, 315 of 500 targeted children were measured. Body mass index (BMI) increased substantially over time (p<0.001), indicating a further rise in obesity into the secondary school years. Two new indicators of obesity were also measured. Waist circumference scores rose as substantially as BMI (p<0.001), and may be of particular significance given the association between abdominal girth in adults and cardiovascular morbidity. International Obesity Task Force measures were found to be more stringent than previous criteria, with no significant change noted over the time period.

Adolescent↗
PubMed2004

TPIT mutations are associated with early-onset, but not late-onset isolated ACTH deficiency.

OBJECTIVE: Congenital isolated ACTH deficiency (IAD) is a rare inherited disorder that is clinically and genetically heterogeneous. Patients are characterised by low or absent cortisol production secondary to low plasma ACTH despite normal secretion of other pituitary hormones and the absence of structural pituitary defects. Onset may occur in the neonatal period, but may first be observed in later childhood. Recently, mutations in the TPIT gene, a T-box factor selectively expressed in developing corticotroph cells, have been found in cases of early-onset IAD. DESIGN: Here we report the screening of the TPIT gene in seven patients with IAD, four of whom had neonatal onset. METHODS: Genomic DNA was extracted and the sequences of the 8 TPIT exons and their intron/exon junctions were determined by automated sequencing. RESULTS: Two siblings with early-onset IAD were both compound heterozygotes for mutations in exons 2 and 6. The missense mutation (Met86Arg) in exon 2 within the T-box (or DNA binding domain) is predicted to disrupt DNA binding. A frameshift mutation in exon 6 (782delA) introduces a premature stop codon and is likely to lead to a non-functional truncated protein. No nucleotide changes were observed in exonic sequences in the other two early- or the three later-onset cases. Fifteen single nucleotide polymorphisms that were not predicted to change the TPIT transcript were also detected. CONCLUSIONS: These findings provide a further illustration of the genetic heterogeneity of IAD and are highly suggestive of one or more other genes being implicated in this disorder.

Adrenocorticotropic Hormone↗
PubMed2003

The expression of P-glycoprotein does influence the distribution of novel fluorescent compounds in solid tumour models.

Solid tumours display a complex drug resistance phenotype that involves inherent and acquired mechanisms. Multicellular resistance is an inherent feature of solid tumours and is known to present significant barriers to drug permeation in tumours. Given this barrier, do acquired resistance mechanisms such as P-glycoprotein (P-gp) contribute significantly to resistance? To address this question, the multicellular tumour spheroid (MCTS) model was used to examine the influence of P-gp on drug distribution in solid tissue. Tumour spheroids (TS) were generated from either drug-sensitive MCF7(WT) cells or a drug-resistant, P-gp-expressing derivative MCF7(Adr). Confocal microscopy was used to measure time courses and distribution patterns of three fluorescent compounds; calcein-AM, rhodamine123 and BODIPY-taxol. These compounds were chosen because they are all substrates for P-gp-mediated transport, exhibit high fluorescence and are chemically dissimilar. For example, BODIPY-taxol and rhodamine 123 showed high accumulation and distributed extensively throughout the TS(WT), whereas calcein-AM accumulation was restricted to the outermost layers. The presence of P-gp in TS(Adr) resulted in negligible accumulation, regardless of the compound. Moreover, the inhibition of P-gp by nicardipine restored intracellular accumulation and distribution patterns to levels observed in TS(WT). The results demonstrate the effectiveness of P-gp in modulating drug distribution in solid tumour models. However, the penetration of agents throughout the tissue is strongly determined by the physico-chemical properties of the individual compounds.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2003

Bradykinin causes hypotension by activating pulmonary sympathetic afferents in the rabbit.

Bradykinin (BK) activates sympathetic afferents in the heart, intestine, and kidney, and it alters hemodynamics. However, we know little about the influence of pulmonary sympathetic afferents on circulation. Activation of pulmonary afferents by directly injecting stimulants into the lung parenchyma permits examination of reflexes that originate in the lung without confounding effects from the systemic circulation. In the present study, we tested the hypothesis that pulmonary sympathetic afferents exert a significant influence on hemodynamics. We examined reflex effects of injecting BK (1 microg/kg in 0.1 ml) into the lung parenchyma on circulation in anesthetized, open-chest, artificially ventilated rabbits. BK significantly decreased mean arterial blood pressure (BP) (27 +/- 3 mmHg) and heart rate (19 +/- 4 beats/min). Both effects remained after bilateral vagotomy. To rule out possible direct systemic vasodilation by BK, we examined renal sympathetic nerve activity (RSNA) in response to BK injection and examined BP responses to injection of ACh (0.1 ml of 10-4 M). BK suppressed the RSNA before and after vagotomy. ACh did not change BP when injected into the lung parenchyma, but it decreased BP (31 +/- 3 mmHg) when injected into the right atrium. Our data indicate that activating pulmonary sympathetic afferents reflexly suppresses hemodynamics.

Acetylcholine↗
PubMed2003

Rural general practitioner preceptors--how can effective undergraduate teaching be supported or improved?

INTRODUCTION: General practitioners (GPs) as rural GP-Preceptors play an important role in medical student teaching within the Discipline of General Practice, University of Tasmania, Australia. As well a significant teaching role, they are responsible for apportioning 20% of the mark medical students receive in the General Practice examination at the end of the rotation. The contribution of the student-rural GP preceptor relationship to recruiting and retaining rural GPs has been acknowledged. Despite these important responsibilities, as honorary teaching staff rural GP preceptors receive no formal training in undergraduate education or assessment, nor did they receive formal peer support. METHOD: To address the lack of educational preparation of GP-preceptors, and in accordance with the stringent teaching and assessment standards of the Australian Medical School Accreditation, a tripartite approach was taken to educational skills development among rural GP-preceptors. The Discipline of General Practice conducted a needs-analysis of 64 rural GP-preceptors, and an evaluation by questionnaire of the teaching efficacy of those 64 rural GP-Preceptors and 76 urban GP-preceptors by 64 final-year medical students after their 3-week rural and urban GP attachments. The second intervention, based on the assessment and evaluation findings, was devised and implemented by the University Department of Rural Health. A series of workshops comprised the interdisciplinary educational and support program for GP preceptors, entitled Preceptor Onsite Preparation Program for Information Education and Support, or POPPIES. RESULTS: The rural GP-preceptor needs analysis indicated that the majority of rural preceptors had no clear understanding of how what they taught fitted into the overall curriculum; they believed that their role as a clinical teacher had not been clearly defined by the program director; and also that undergraduate students had little understanding of what they needed to learn during their attachments. In contrast, preceptors believed they understood what students needed to learn; they were confident in performing the role of preceptor; and were familiar with adult learning principles, goal setting processes, effective student evaluation and the provision of appropriate performance feedback. Evaluation of feedback from students revealed that while rural GP preceptors performed well overall in regard to providing quality teaching and learning experiences, there was a significant spread of scores across all criteria, and approximately 15%-25% of students perceived various aspects of their attachment to be mediocre or poor. CONCLUSION: The combined results of the medical student questionnaire and rural GP-preceptor survey indicated both a need and a desire for educational skills development among rural GP-preceptors. On this basis, the interdisciplinary educational and support program for GP-preceptors (POPPIES) was developed and implemented as a series of workshops throughout rural Tasmania. Although no objective data are yet available about teaching outcomes as a result of POPPIES workshops, preliminary responses from attendee GP preceptors indicated that the workshops were effective in addressing educational needs, and in providing rural clinical teachers with professional teaching development.

Journal Article↗