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Biomedical subjects

R Jones

Publications and source records attributed to R Jones.

At least 145 records · Page 8Linked to original sources

Human perceptions of sports equipment under playing conditions.

Assessment of the 'performance' of sports equipment is generally derived from physical and technical parameters, such as power, speed, distance and accuracy. However, from a psychological perspective, players need to feel comfortable with their equipment and confident in its properties. These factors can only be measured through the subjective assessment of individual perceptions. Focusing on a group of elite golfers, this study presents a formalized approach for eliciting and structuring players' descriptions of their perception of sports equipment. Qualitative methods of inquiry were used to generate perceptions from a group of professional golfers (n = 15) during play testing. The equipment characteristics of significance to the golfers emerged from an inductive analysis of their responses. However, although this method of representation of the results helped to identify the key components or dimensions of a player's subjective perception, it was unable to determine potential relationships between the dimensions. With this in mind, a new technique, called 'structured relationship modelling', was developed. Ten general dimensions emerged from the analysis, of which three are presented here together with a section of the relationship model. The results demonstrate the effectiveness of qualitative techniques for eliciting human perceptions and of structured relationship models for representation of the associations found.

Adult↗

Why can't you scientists leave things alone? Science questioned in British films of the post-war period (1945-1970).

Considerable attention has been paid to the representation of scientists as villains in horror and science fiction films, and to the part this has played in creating the public perception of scientists. But science and scientists have also been represented in films which do not fit readily with the conventions of these genres, and these "mainstream" films allow a more detailed investigation of the public perception of science at the time they were made. This paper examines a number of British mainstream films portraying scientists and science from the period 1945-1970 to see in what ways the conduct of science was being questioned. A concern with the political control of science and the resulting secrecy is evident in a number of the films. The criticism of scientists seems to come from two contradictory directions. Scientists were either seen as too detached and unconcerned about the consequences of their work, or they were too emotional and insufficiently objective. This is in part explained by newer, less deferential attitudes to science co-existing with the older, heroic view during the period under study.

History, 20th Century↗

Diffusion barriers in ram and boar sperm plasma membranes: directionality of lipid diffusion across the posterior ring.

The plasma membrane of mammalian spermatozoa, like that of other differentiated cells, is compartmentalized into discrete regions or domains that are biochemically and functionally distinct from one another. Physical structures within the membrane, such as the posterior ring at the juncture of the sperm head and tail, have long been thought to act as diffusion barriers to help segregate important molecules required for fertilization within specific domains and to regulate migration of molecules between domains. In this investigation, we used a quantitative photobleaching technique (video-FRAP) to assess the efficacy of the posterior ring as a barrier to exchange of lipids between the postacrosomal and midpiece plasma membranes. A lipid reporter probe (1,1'-diduodecyl-3,3,3', 3'-tetramethylindocarbocyanine; DiIC(12)) was incorporated into the plasma membrane of live ram and boar spermatozoa, and the directionality of its diffusion across the posterior ring was measured by line-profile analysis. Results showed that DiIC(12) was able to traverse the posterior ring from the direction of the postacrosomal plasma membrane and to diffuse onto the midpiece plasma membrane. These results suggest that the posterior ring is not an immutable barrier to lipid exchange in mature spermatozoa and that there are other mechanisms for maintaining in-plane lipid asymmetry, such as differential phase behavior and interaction with the submembranous cytoskeleton.

Acrosome↗

Expression of the adhesion molecules Mac-1 and L-selectin on neutrophils in acute pancreatitis is protease- and complement-dependent.

OBJECTIVE: To examine the effect of pancreatic proteases on the expression of the adhesion molecules Mac-1 and l-selectin on neutrophils, and the role of complement activation in this process. SUMMARY BACKGROUND DATA: Sequestration of neutrophils in the pancreatic and pulmonary microvasculature characterizes acute pancreatitis. METHODS: Serum was collected from inbred rats after induction of necrotizing pancreatitis; trypsinogen activation peptide was measured to quantify trypsin activation. Normal rat serum was also collected and subjected to limited trypsin digestion with and without the addition of complement inhibitor. Both groups of sera were incubated in vitro with healthy leukocytes. Expression of Mac-1 and L-selectin on neutrophils was measured quantitatively by flow cytometry. To assess the consequences of these events in vivo, trypsinated serum with or without complement inhibition or control serum was infused intravenous into rats. Soybean trypsin inhibitor was added to serum before injections to block residual trypsin activity. Pancreatic and pulmonary injury was quantitated by histology, measurement of edema, and myeloperoxidase activity. RESULTS: Mac-1 expression on neutrophils incubated with pancreatitis serum was increased compared with controls, whereas L-selectin was decreased. Neutrophils incubated with trypsinated serum also showed upregulation of Mac-1 and downregulation of L-selectin, particularly with trypsin at 10(-4) mol/L. Addition of soluble complement receptor 1 abrogated both Mac-1 upregulation and L-selectin downregulation. Lungs of animals injected with trypsinated serum showed increased edema and myeloperoxidase activity, which were reduced by soluble complement receptor 1. CONCLUSIONS: Trypsin-generated complement activation participates in the upregulation of Mac-1 and shedding of L-selectin on neutrophils in acute pancreatitis. Protease or complement inhibition may be effective in preventing leukocyte migration and subsequent local and remote organ injury.

Analysis of Variance↗

Nebulized sildenafil is a selective pulmonary vasodilator in lambs with acute pulmonary hypertension.

OBJECTIVE: To determine whether inhalation of aerosolized sildenafil with and without inhaled nitric oxide (NO) causes selective pulmonary vasodilation in a sheep model of pulmonary hypertension. DESIGN: A controlled laboratory study in instrumented, awake, spontaneously breathing lambs. SETTING: Animal research laboratory affiliated with a university hospital. SUBJECT: Twenty Suffolk lambs. INTERVENTIONS: Lambs were instrumented with a carotid artery catheter, a pulmonary artery catheter, and a tracheostomy tube and studied awake. After baseline measurements, pulmonary hypertension was induced by the continuous infusion of U46619, a thromboxane A2 analog. After breathing three concentrations of inhaled NO (2, 5, and 20 ppm), lambs were divided into two groups. Group 1 (n = 7) breathed aerosols containing 1, 10, and 30 mg of sildenafil alone, and group 2 (n = 4) simultaneously breathed NO (2 and 5 ppm) and aerosols containing 10 mg of sildenafil. Hemodynamic measurements were obtained before and at the end of each drug administration. Venous admixture was calculated, and plasma cyclic guanosine monophosphate and sildenafil concentrations were measured. MEASUREMENTS AND MAIN RESULTS: Aerosols containing 10 mg and 30 mg of sildenafil selectively decreased the pulmonary artery pressure by 21% +/- 3% and 26% +/- 3%, respectively (p < .05 vs. baseline pulmonary hypertension). When 10 mg of sildenafil was inhaled while simultaneously breathing 2 ppm and 5 ppm NO, the pulmonary artery pressure decreased by 35% +/- 3% and 43% +/- 2% (p < .05 vs. baseline pulmonary hypertension). Inhaled sildenafil did not impair systemic oxygenation, increase right-to-left intrapulmonary shunting, or impair the ability of inhaled NO to reduce right-to-left shunting. CONCLUSIONS: Nebulized sildenafil is a selective pulmonary vasodilator that can potentiate the pulmonary vasodilating effects of inhaled NO.

Acute Disease↗

Single-dose gatifloxacin compared with ofloxacin for the treatment of uncomplicated gonorrhea: a randomized, double-blind, multicenter trial.

BACKGROUND: Treatment of gonorrhea is complicated by widespread resistance of Neisseria gonorrhoeae to antimicrobial agents of choice, including decreased susceptibility to ciprofloxacin. GOAL: To demonstrate the efficacy and safety of gatifloxacin, a novel 8-methoxy fluoroquinolone antibiotic, compared with ofloxacin in treating patients with uncomplicated gonococcal infection. STUDY DESIGN: In a double-blind, randomized (2:2:1), controlled trial, 340 men and 388 women with uncomplicated gonorrhea who were 16 years or older received a single oral dose of gatifloxacin (400 mg or 600 mg) or ofloxacin (400 mg). Primary analysis of efficacy was based on bacteriologic eradication from sites of infection. Secondary analyses examined clinical response and adverse event profiles. RESULTS: Bacteriologic eradication rates for gatifloxacin in evaluable men with urethral gonorrhea were 99% (400 mg) and 100% (600 mg) versus 100% for ofloxacin (n = 117, 122, and 55, respectively; P = ns). Eradication rates in evaluable women with endocervical gonorrhea were 99% for both 400 mg and 600 mg gatifloxacin versus 100% for ofloxacin (n = 101, 104, and 55, respectively; P = ns). Eradication rates were 100% for both rectal (n = 43) and pharyngeal (n = 31) infection across all treatment groups. All three drug regimens were well tolerated and exhibited similar clinical response profiles. CONCLUSION: Gatifloxacin is safe and effective as a single 400-mg or 600-mg dose for the treatment of uncomplicated gonorrhea. Similar efficacy rates were observed with the 400-mg and 600-mg doses. A single 400-mg dose can be recommended for treatment of uncomplicated gonorrhea.

Administration, Oral↗

The influence of dose of angiotensin I-converting enzyme inhibitor on systolic blood pressure variability in heart failure: a substudy of the Assessment of Treatment with Lisinopril and Survival in heart failure (ATLAS) trial.

UNLABELLED: Heart failure is associated with a decreased variability in circadian systolic blood pressure. ACE inhibitors have been shown to be beneficial in CHF. However, the effect of the magnitude of the dose of ACE inhibitor on blood pressure variability has not been reported. The objective of this sub-study of the ATLAS trial was to determine if there was a difference in effect on systolic blood pressure variability of two doses (35mg, 'high'; and, 5mg, 'low') of the ACE inhibitor, lisinopril, in patients with heart failure (class II-IV; NYHA). Criteria for inclusion were: symptomatic heart failure (class II-IV; NYHA), left ventricular ejection fraction < or = 30%, and 2 months of conventional therapy with diuretics with, or without, digoxin. Twenty-four hour ambulatory blood pressure was recorded prior to randomization and after peak titration (4 weeks) of the study drug for analysis of variability of systolic blood pressure variability. The high dose of lisinopril was associated with greater variability of 24 h systolic blood pressure as noted by inspection of the 24 h recordings or calculation of the blood pressure variability index (P < 0.05). The greater variability in SBP was not associated with a difference in mean 24 h arterial blood pressure. CONCLUSIONS: Variation in circadian systolic blood pressure is useful in reflecting the influence of the magnitude of dose of the ACE inhibitor lisinopril on the pharmacodynamics of patients with heart failure.

Angiotensin-Converting Enzyme Inhibitors↗

Initial validation of a diagnostic questionnaire for gastroesophageal reflux disease.

OBJECTIVES: Brief, reliable, and valid self-administered questionnaires could facilitate the diagnosis of gastroesophageal reflux disease in primary care. We report the development and validation of such an instrument. METHODS: Content validity was informed by literature review, expert opinion, and cognitive interviewing of 50 patients resulting in a 22-item survey. For psychometric analyses, primary care patients completed the new questionnaire at enrollment and at intervals ranging from 3 days to 3 wk. Multitrait scaling, test-retest reliability, and responsiveness were assessed. Predictive validity analyses of all scales and items used specialty physician diagnosis as the "gold standard." RESULTS: Iterative factor analyses yielded three scales of four items each including heartburn, acid regurgitation, and dyspepsia. Multitrait scaling criteria including internal consistency, item interval consistency, and item discrimination were 100% satisfied. Test-retest reliability was high in those reporting stable symptoms. Scale scores significantly changed in those reporting a global change. Regressing specialty physician diagnosis on the three scales revealed significant effects for two scales (heartburn and regurgitation). Combining the two significant scales enhanced the strength of the model. Symptom response to self-directed treatment with nonprescription antisecretory medications was highly predictive of the diagnosis also, although the item demonstrated poor validity and reliability. CONCLUSIONS: A brief, simple 12-item questionnaire demonstrated validity and reliability and seemed to be responsive to change for reflux and dyspeptic symptoms.

Adult↗

Coverage of neonatal screening: failure of coverage or failure of information system.

OBJECTIVES: To evaluate neonatal screening coverage using data routinely collected on the laboratory computer. SUBJECTS: 90 850 births in 14 North East Thames community provider districts over a 21 month period. METHODS: Births notified to local child health computers are electronically copied to the neonatal laboratory computer system, and incoming Guthrie cards are matched against these birth records before testing. The computer records for the study period were processed to estimate the coverage of the screening programme. RESULTS: Out of an estimated 90 850 births notified to child health computers, all but 746 (0.82%) appeared to have been screened or could be otherwise accounted for (0.14% in non-metropolitan districts, 0.39% in suburban districts, and 1.68% in inner city districts). A further 893 resident infants had been tested, but could not be matched to the list of notified resident births. The calculated programme coverage already exceeds the 99.5% National Audit Programme standard in 7/14 districts. Elsewhere it is not clear whether it is coverage or recording of coverage that is low. CONCLUSION: Previous reports of low coverage may have been exaggerated. High coverage can be shown using routine information systems. Design of information systems that deliver accurate measures of coverage would be more useful than comparison of inadequately measured coverage with a national standard. The new NHS number project will create an opportunity to achieve this.

Birth Certificates↗

A new variant of Carney's triad: phaeochromocytoma and chondrosarcoma.

A 61 year old hypertensive woman presented in 1986 with a right scapular chondrosarcoma. She developed type 1 diabetes mellitus in 1991 and suffered a stroke in 1991. Chest radiography showed pulmonary metastases in 1997. Further radiological staging detected a right sided phaeochromocytoma, which was subsequently removed in 1998. Before this, repeated urine estimations of vanillylmandelic acid had been normal. Her diabetes was cured by adrenalectomy. It is believed that the combination of phaeochromocytoma and extrapulmonary chondrosarcoma represents a new variant of Carney's triad.

Adrenal Gland Neoplasms↗

Interactions between mouse ZP2 glycoprotein and proacrosin; a mechanism for secondary binding of sperm to the zona pellucida during fertilization.

The mouse zona pellucida glycoprotein, mZP2, is thought to be the secondary receptor on eggs for retention of acrosome-reacted sperm during fertilization. Here, we present evidence that one of its complementary binding proteins on sperm is proacrosin/acrosin. mZP2 binds to proacrosin null sperm considerably less effectively than to wild-type sperm. Binding is mediated by a strong ionic interaction between polysulphate groups on mZP2 and basic residues on an internal proacrosin peptide. The stereochemistry of both sulphate groups and basic amino acids determines the specificity of binding. Structurally relevant sulphated polymers and suramin, a polysulphonated anticancer drug, compete with mZP2 for complementary binding sites on proacrosin/acrosin in solid-phase binding assays. The same competitors also displace attached sperm from the zona pellucida of eggs in an in vitro fertilization system. This combination of genetic, biochemical and functional data supports the hypothesis that mZP2-proacrosin interactions are important for retention of acrosome-reacted sperm on the egg surface during fertilization. Safe mimetics of suramin have potential as non-steroidal antifertility agents.

Acrosin↗

Oral uracil-tegafur: an alternative to intravenous 5-fluorouracil?

The fluoropyrimidines have been used in the treatment of a number of tumour types over the past 40 years. Particular attention has focused on the use of 5-fluorouracil (5-FU) in colorectal cancer for which, until recently, there has been a lack of other effective chemotherapy. In an attempt to optimise the efficacy of fluoropyrimidines, a number of approaches have been used. These include alternative methods of iv. scheduling, the use of co-factors and the development of oral compounds. The aim of oral agents is to satisfy patient preference while maintaining the efficacy of sustained drug exposure seen with prolonged or continuous infusions of iv. 5-FU. One such oral compound is uracil-tegafur (UFT), which combines tegafur (ftorafur, a 5-FU prodrug) and uracil in a 1:4 molar ratio. UFT first entered Phase I trials in Japan over 20 years ago but has only recently received significant exposure in Phase II and III trials. Results from a number of Phase III studies in Europe and in the US are now becoming available. With UFT recently approved for colorectal cancer in many European countries, although not in the US, it is timely to review the current situation and future prospects for this agent.

Administration, Oral↗

Symptom and health-related quality-of-life measures for use in selected gastrointestinal disease studies: a review and synthesis of the literature.

Patient-rated symptom and health-related quality-of-life (HR-QOL) outcomes are important end-points for clinical trials of medical treatments for gastrointestinal (GI) disorders. Based on this review, patient outcomes research is focused on gastroesophageal reflux disease and dyspepsia, with a growing interest in irritable bowel syndrome but little research in gastroparesis. State-of-the-art for patient-rated symptom scales is rudimentary with an abundance of scales and little attention to systematic instrument development or comprehensive psychometric evaluation. Generally, disease-specific HR-QOL measures have been more systematically developed and evaluated psychometrically, but few have been incorporated into clinical trials. More comprehensive outcome assessments are needed to determine the effectiveness of new medical treatments for functional GI disorders. Future clinical trials of GI disorders should combine clinician assessments of outcomes and symptoms with patient-rated symptom and HR-QOL end-points.

Clinical Trials as Topic↗

Low proliferative rate of invasive node-negative breast cancer predicts for a favorable outcome: a prospective evaluation of 669 patients.

This study was designed to compare outcome in terms of disease-free survival (DFS) in women with histologically negative axillary lymph nodes and documented low proliferative rate cancer to other well-defined prognostic factors including type of adjuvant treatment. Between 1988 and 1998, we studied 669 patients with invasive node-negative breast cancer up to 5 cm in size and low proliferative rate measured by flow cytometry to determine S-phase fraction (SPF) or by histochemistry (Ki67/MIB1). At a median follow-up of 53 months, 5-year DFS for the entire group was 94% and did not differ significantly by type of systemic adjuvant treatment: none (133 patients, 95% DFS), tamoxifen (441 patients, 94% DFS), or chemotherapy with doxorubicin and cyclophosphamide (95 patients, 92% DFS). In a multivariate prognostic factor analysis, only tumor size was significant; 5-year DFS was 96% for T1N0 cancer versus 89% for T2N0 cancer (P = 0.01). We have prospectively confirmed that a low rate of proliferation as measured by SPF or MIB1 determination confers an excellent prognosis in invasive node-negative breast cancer up to 5 cm in size, regardless of adjuvant treatment.

Adult↗

Alternative forages--back to the future.

The BSE crisis, restrictions over export of UK beef and bans on animal-derived concentrate feeds are driving agriculture in the UK 'back' towards more sustainable, low input systems for feeding cattle and sheep using 'natural' home-grown forages. Research is in progress to answer some of the questions surrounding the use of protein- and energy-rich alternative forages as feeds for ruminants.

Agriculture↗

A continuous curriculum for general practice? Proposals for undergraduate-postgraduate collaboration.

The development of a seamless general practice 'spiral' curriculum, in which topics may be revisited at different levels of intensity and complexity during the learning process, has been discussed in the context of undergraduate-postgraduate co-operation. Although the lifelong curriculum for all doctors contains a number of core competencies that aim to produce a 'stem' doctor, concerns remain about the effects of excessive reductionism. It is therefore essential that the content and delivery of the spiral curriculum ensure that intellectual interest is nurtured, by containing both taught theory and training in a hospital context. The opportunity for generalists to teach core competencies such that general practice is at the centre of the undergraduate curriculum--emphasising working within primary health care teams in teaching and training practices--is an ideal area for undergraduate-postgraduate co-operation. The use of the directly observed measures of performance would bring the undergraduate approach to assessment closer to that used in postgraduate general practice. However, supporting the tutors' network is crucial in undergraduate departments where much can be gained by joint working with postgraduate colleagues.

Curriculum↗

An integrated restriction fragment length polymorphism--amplified fragment length polymorphism linkage map for cultivated sunflower.

Restriction fragment length polymorphism (RFLP) maps have been constructed for cultivated sunflower (Helianthus annuus L.) using three independent sets of RFLP probes. The aim of this research was to integrate RFLP markers from two sets with RFLP markers for resistance gene candidate (RGC) and amplified fragment length polymorphism (AFLP) markers. Genomic DNA samples of HA370 and HA372, the parents of the F2 population used to build the map, were screened for AFLPs using 42 primer combinations and RFLPs using 136 cDNA probes (RFLP analyses were performed on DNA digested with EcoRI, HindIII, EcoRV, or DraI). The AFLP primers produced 446 polymorphic and 1101 monomorphic bands between HA370 and HA372. The integrated map was built by genotyping 296 AFLP and 104 RFLP markers on 180 HA370 x HA372 F2 progeny (the AFLP marker assays were performed using 18 primer combinations). The HA370 x HA372 map comprised 17 linkage groups, presumably corresponding to the 17 haploid chromosomes of sunflower, had a mean density of 3.3 cM, and was 1326 cM long. Six RGC RFLP loci were polymorphic and mapped to three linkage groups (LG8, LG13, and LG15). AFLP markers were densely clustered on several linkage groups, and presumably reside in centromeric regions where recombination is reduced and the ratio of genetic to physical distance is low. Strategies for targeting markers to euchromatic DNA need to be tested in sunflower. The HA370 x HA372 map integrated 14 of 17 linkage groups from two independent RFLP maps. Three linkage groups were devoid of RFLP markers from one of the two maps.

Chromosome Mapping↗