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Biomedical subjects

R Jones

Publications and source records attributed to R Jones.

At least 127 records · Page 7Linked to original sources

Fine mapping and genetic heterogeneity in the pure form of autosomal dominant familial spastic paraplegia.

We evaluated seven families segregating pure, autosomal dominant familial spastic paraplegia (SPG) for linkage to four recently identified SPG loci on chromosomes 2q (1), 8q (2), 12q (3), and 19q (4). These families were previously shown to be unlinked to SPG loci on chromosomes 2p, 14q, and 15q. Two families demonstrated linkage to the new loci. One family (family 3) showed significant evidence for linkage to chromosome 12q, peaking at D12S1691 (maximum lod = 3.22). Haplotype analysis of family 3 did not identify any recombinants among affected individuals in the 12q candidate region. Family 5 yielded a peak lod score of 2.02 at marker D19S868 and excluded linkage to other known SPG loci. Haplotype analysis of family 5 revealed several cross-overs in affected individuals, thereby potentially narrowing the SPG12 candidate region to a 5-cM region between markers D19S868 and D19S220. Three of the families definitively excluded all four loci examined, providing evidence for further genetic heterogeneity of pure, autosomal dominant SPG. In conclusion, these data confirm the presence of SPG10 (chromosome 12), potentially reduce the minimum candidate region for SPG12 (chromosome 19q), and suggest there is at least one additional autosomal dominant SPG locus.

Chromosome Mapping↗

Application of the stretched exponential function to fluorescence lifetime imaging.

Conventional analyses of fluorescence lifetime measurements resolve the fluorescence decay profile in terms of discrete exponential components with distinct lifetimes. In complex, heterogeneous biological samples such as tissue, multi-exponential decay functions can appear to provide a better fit to fluorescence decay data than the assumption of a mono-exponential decay, but the assumption of multiple discrete components is essentially arbitrary and is often erroneous. Moreover, interactions, both between fluorophores and with their environment, can result in complex fluorescence decay profiles that represent a continuous distribution of lifetimes. Such continuous distributions have been reported for tryptophan, which is one of the main fluorophores in tissue. This situation is better represented by the stretched-exponential function (StrEF). In this work, we have applied, for the first time to our knowledge, the StrEF to time-domain whole-field fluorescence lifetime imaging (FLIM), yielding both excellent tissue contrast and goodness of fit using data from rat tissue. We note that for many biological samples for which there is no a priori knowledge of multiple discrete exponential fluorescence decay profiles, the StrEF is likely to provide a truer representation of the underlying fluorescence dynamics. Furthermore, fitting to a StrEF significantly decreases the required processing time, compared with a multi-exponential component fit and typically provides improved contrast and signal/noise in the resulting FLIM images. In addition, the stretched-exponential decay model can provide a direct measure of the heterogeneity of the sample, and the resulting heterogeneity map can reveal subtle tissue differences that other models fail to show.

Animals↗

Challenges with studies investigating longevity of dental restorations--a critique of a systematic review.

OBJECTIVES: A systematic review is a method of evaluating the published and unpublished literature relating to a specific area or topic. The objectives of this paper are to identify and discuss problems encountered in synthesising the available literature; and to make recommendations for the future conduct and reporting of clinical trials that aim to determine the longevity of dental restorations. DATA SOURCES: Studies were identified by a wide search of published and unpublished material in any language using a large number of general and specialist data bases, hand searching of key dental journals and searching of abstracts from conference proceedings. STUDY SELECTION: Pre-defined inclusion criteria based on objective outcome measures of restoration longevity and study designs were applied to determine study selection. CONCLUSIONS: A review of the longevity of dental restorations completed recently encountered substantial problems in designing an appropriate protocol to address this issue. The review found that many of the factors reported previously as affecting restoration longevity could not be confirmed using the agreed systematic review protocol that incorporated an objective study design. Further, the multiplicity of study designs, and reporting methods found in the literature made meta-analyses impossible. A proforma is proposed in order to aid the design of future research into the longevity of restorations.

Dental Materials↗

Biocompatibility and performance of the Wallstent and several covered stents in a sheep iliac artery model.

PURPOSE: To compare the biocompatibility and performance of various stent-grafts to those of a bare stent in an ovine model with a subchronic (3 months) endpoint. MATERIALS AND METHODS: Three different types of stent-grafts (ePTFE/nitinol, n = 8; polyester/nitinol, n = 8; and polycarbonate urethane/cobalt-alloy, n = 8) and a bare stent as a control (Ni-Co-Ti-steel-alloy, n = 8) were implanted in the iliac arteries in eight female sheep. One type of each stent-graft was implanted per animal, two implants at each side. The implantation sites for each type varied from animal to animal. Angiographic control and intravascular ultrasound (IVUS) imaging were performed before and after implantation, after 2 months, and before explantation at 3 months and were used to characterize patency and to assess intimal hyperplasia. After 3 months, the implants were retrieved and subjected to histologic evaluation (after methacrylate embedding, cutting, and histologic staining) to characterize the biologic response. RESULTS: Implantation was technically successful in all procedures. At 2 and 3 months after implantation, all segments in which stents had been implanted were patent. Marked neointima formation was found in the polyester-covered stent-graft that showed significant luminal narrowing of 50%, compared to the ePTFE-covered (24%) and polycarbonate urethane-covered endoprostheses (22%), as well as the bare stent (Wallstent; 9%; P < .001). A minimal inflammatory vessel wall reaction was demonstrated for the polyester-covered and ePTFE-covered endoprostheses; the polycarbonate urethane-covered stent-graft's response was demonstrable but not significantly different from that of the Wallstent. At 3 months, the ePTFE-covered stent-graft showed incomplete (>90%) endothelial coverage; in the other endoprostheses, complete but partially immature endothelialization was found. CONCLUSION: All stent-grafts induced an inflammatory vessel wall reaction with neointimal hyperplasia. The polyester-covered endoprosthesis caused a marked reaction with 50% luminal stenosis. Endothelialization was retarded with the ePTFE-covered stent-graft. The bare stent performed best in regard to neointimal formation and caused the least inflammatory response.

Alloys↗

Aqueous sonolytic decomposition of polycyclic aromatic hydrocarbons in the presence of additional dissolved species.

Sonochemical degradation of aqueous polycyclic aromatic hydrocarbons (PAHs) results in a first-order loss of the PAHs (k = 0.010-0.027 s-1). When sonication occurred in the presence of other organic compounds, the degradation rate constant was reduced quite dramatically. This reduction is believed to come about through scavenging of radicals by the matrix chemical. When oxygen was bubbled into the PAH solution before sonication, the degradation rate constant was elevated. Nitrogen purging resulted in decreased rate constants. These results indicate that oxygen was an important precursor in the degradation of the PAHs. Organic compounds, including humic acid, benzoic acid, and sodium dodecyl sulfate, decreased PAH degradation rate constants by scavenging oxygen derived reactive transients.

Indicators and Reagents↗

Hand function of C6 and C7 tetraplegics 1 - 16 years following injury.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To quantify the hand function of C6 and C7 tetraplegics 1 - 16 years after injury. SETTING: Patients were assessed in their homes. METHODS: Medical records of patients admitted to the Prince Henry Hospital Spinal Injuries Unit between 1984 and 1999 were used to identify all patients with C6 or C7 tetraplegia at 3 months post injury. Sixty-five patients (107 hands) were identified in this way. Forty-seven patients (81 hands) were located and agreed to partake in the study, and seven (nine hands) had died. Thus 81% of patients (83% of hands) still alive at follow-up were assessed. MAIN OUTCOME MEASURES: Unilateral hand function was assessed with the Grasp and Release Test (GRT) and a 10 item Activities of Daily Living (ADL) Test. Prevalance and severity of contractures, lateral grasp (key grip) strength and extensibility of the extrinsic finger flexor muscles were also determined. RESULTS: All hands except one had been managed without surgical intervention. The median number of ADL tasks successfully completed was 9/10 (interquartile range=8 - 10) and the median number of objects successfully manipulated in the GRT was 3/6 (IQ range=3 - 5). Lateral grasp was poor (74% and 75% of hands could not use a lateral grasp to move the paperweight or depress the fork in the GRT, respectively), and the prevalence of contractures was low (53% of hands had full passive range of motion). CONCLUSION: In the long term, most C6 and C7 tetraplegics attain a high level of hand function despite poor lateral grasps.

Activities of Daily Living↗

Surveillance of antimicrobial resistance--what, how and whither?

OBJECTIVE: To express the views of a working party held to consider antibiotic resistance surveillance systems, their strengths and weaknesses, and their current and future applications. METHODS: The participants, all of whom were experienced in this field, discussed the development of surveillance systems in relation to the increasing prevalence of resistance to antibacterial agents and the current interest in surveillance systems shown by many official bodies, in both the human and veterinary fields. The problems inherent in surveillance systems were considered together with the applications of different systems. RESULTS: The properties of good antibiotic resistance surveillance systems were defined. Surveillance systems vary widely from those with a narrow base, focusing on few organisms in one disease area, to those covering many diseases, many organisms (including normal flora) and many compounds. Whatever their design, they should be able to detect significant differences and shifts in susceptibility to various antibacterial agents, and the information derived from them should reach as many interested parties as possible in a timely manner. In using this information to decide strategies, criteria for action need to be determined by pragmatic consensus. Funding remains a major problem, with few large studies being supported by official bodies in spite of their professed enthusiasm for surveillance. In consequence, many current systems are funded by the pharmaceutical industry and are of necessity restricted in their focus. CONCLUSIONS: Antibiotic resistance surveillance studies should and can be well planned and well executed. Many current systems suffer from well-recognized but uncorrected biases. Consortium funding will be necessary for large schemes to be successful. There is no "ideal" surveillance system.

Animals↗

Review article: acid suppression in the management of gastro-oesophageal reflux disease--an appraisal of treatment options in primary care.

Gastro-oesophageal reflux disease (GERD) is one of the most common conditions presenting to the primary care physician. Despite progress in understanding and treatment of the disease, strategies for capitalizing on these advances are less well developed. In many practices, H2-receptor antagonists still remain the most widely prescribed treatment for GERD, despite the availability of the more effective acid-suppressant proton pump inhibitors. This review examines the relative efficacies of acid-suppressant drugs in minimizing oesophageal acid exposure and outlines the evidence for the superiority of proton pump inhibitors over standard-dose H(2)-antagonists in symptom relief, erosion healing and prevention of relapse in GERD. Current prescribing patterns and considerations for the general practitioner are also examined. The availability and impact of over-the-counter H(2)-antagonists on the treatment of GERD and their relative cost-effectiveness vs. proton pump inhibitors are also addressed. A hierarchy of drug efficacy (full-dose proton pump inhibitor > half-dose proton pump inhibitor > high-dose H(2)-antagonist > standard-dose H(2)-antagonist or prokinetic) applies in principle to all GERD patients, (with or without oesophagitis). The most effective initial therapy for GERD is also likely to be the most cost-effective one, if treatment failure leads to higher utilization of medical resources. The application of these recommendations to the management of non-endoscoped GERD, endoscopy-negative GERD and low-grade oesophagitis as well as higher grade oesophagitis is also reviewed.

Cost-Benefit Analysis↗

High-dose intrathecal diamorphine for analgesia after Caesarean section.

Forty women undergoing elective Caesarean section under spinal anaesthesia using hyperbaric 0.5% bupivacaine were randomly allocated to receive either 0.5 mg or 1 mg intrathecal diamorphine. All women received diclofenac 100 mg at the end of surgery and morphine via a patient-controlled analgesia system. Oral analgesics were not used. Postoperative analgesia was more prolonged and more reliable in the 1-mg group. Mean time to first analgesia was 10.2 h in the 1-mg group and 6.9 h in the 0.5-mg group, and 45% in the 1-mg group used no morphine, compared with 10% in the 0.5-mg group. Mean morphine consumption over 24 h was 5.2 mg in the 1-mg group and 10.6 mg in the 0.5-mg group. Pain scores all tended to be lower in the 1-mg group but this was only significant at 4 h. There were no serious side-effects. Minor side-effects were common but well tolerated, and the incidence did not differ between the groups. If intrathecal diamorphine is used in combination with rectal diclofenac and without oral analgesia, then 1 mg provides superior analgesia to 0.5 mg without any worsening of the side-effects.

Administration, Rectal↗

Sanitary towel provision and disposal in primary schools.

This study was designed to look at arrangements for menstruating girls in primary schools. We report the results of a questionnaire sent to the head teachers of 344 randomly selected primary schools throughout the UK. Although sanitary towels were available in 90% of schools, most girls had to ask an adult for a towel. Almost 60% of schools had disposal facilities, but in only 43% were facilities situated within individual toilet cubicles. The deficiencies identified in provision for girls in primary schools should be addressed.

Child↗

What role do nurses play in Type 2 diabetes care in the community: a Delphi study.

OBJECTIVES: To identify the views of nurses on their current and future roles in care in the community for people with Type 2 diabetes. METHOD: A two-round Delphi study was used to elicit, and assess consensus on opinions from random samples of practice nurses, with a substantial role in the management of diabetes patients and diabetes specialist nurses. Both groups had defined levels of expertise in diabetes care and worked in Great Britain. The study instrument in round one comprised a questionnaire with 10 statement headings inviting opinions on the nursing role in the management and care of people with Type 2 diabetes. In the second round levels of agreement were elicited from responders on collated opinions from round one. The initial questionnaire also included closed questions to obtain a profile of current care delivered. RESULTS: Responders were 97 practice nurses and 69 diabetes specialist nurses with second round response rates of 93% and 86%, respectively. The 47 themes raised could be grouped under headings of clinical practice, responsibility, communication, knowledge, education/experience, rewards, and patients' roles. Many were common to several statements and both nurse groups. The level of agreement on the themes fed back was high, 85% of the 165 items achieved greater than 80% agreement. Agreement occurred for factors relating to clinical effectiveness, audit, knowledge, education and experience. Dissent occurred both within and between individual nurse groups on issues of responsibility, prescribing, service delivery, resources, and patient factors. CONCLUSIONS: This Delphi study has identified key areas of consensus on the management of care for people with Type 2 diabetes in the community but also areas in which further work needs to be carried out to understand the differences found. Many of the discordant items relate to the separate roles and associated issues of the two nurse groups.

Attitude of Health Personnel↗

Time-domain whole-field fluorescence lifetime imaging with optical sectioning.

A whole-field time-domain fluorescence lifetime imaging (FLIM) microscope with the capability to perform optical sectioning is described. The excitation source is a mode-locked Ti:Sapphire laser that is regeneratively amplified and frequency doubled to 415 nm. Time-gated fluorescence intensity images at increasing delays after excitation are acquired using a gated microchannel plate image intensifier combined with an intensified CCD camera. By fitting a single or multiple exponential decay to each pixel in the field of view of the time-gated images, 2-D FLIM maps are obtained for each component of the fluorescence lifetime. This FLIM instrument was demonstrated to exhibit a temporal discrimination of better than 10 ps. It has been applied to chemically specific imaging, quantitative imaging of concentration ratios of mixed fluorophores and quantitative imaging of perturbations to fluorophore environment. Initially, standard fluorescent dyes were studied and then this FLIM microscope was applied to the imaging of biological tissue, successfully contrasting different tissues and different states of tissue using autofluorescence. To demonstrate the potential for real-world applications, the FLIM microscope has been configured using potentially compact, portable and low cost all-solid-state diode-pumped laser technology. Whole-field FLIM with optical sectioning (3D FLIM) has been realized using a structured illumination technique.

Animals↗

Standardized or real patients to test clinical competence? The long case revisited.

BACKGROUND: In undergraduate clinical examinations, the use of real patients as long cases is being replaced by objective structured clinical examinations (OSCEs) which use simulated scenarios, although we lack published psychometric data on long cases to support the move from real to simulated patients. AIM: To assess candidate performance across two history-taking long cases to estimate the number of cases required for a reliable assessment. Results are compared with psychometric data from an OSCE. SETTING: A final-year qualifying undergraduate clinical examination. METHOD: Two observed history-taking long cases were included, alongside an OSCE. Candidates interviewed two unstandardized real patients. The history-taking part (14 minutes) was observed, uninterrupted, by examiner(s) who assessed data gathering, interviewing, and diagnostic and management skills. The presentation (7 minutes) was unstructured; the examiner(s) intervened as appropriate. Marks were expressed as a percentage of the total possible score and analysed using generalizability theory to estimate intercase reliability. RESULTS: Two examiner pairs independently rated both long cases for 79 (36.7%) of the 214 candidates. Projections based on generalizability theory showed that 10 20-minute cases would give reliabilities of 0.84 for single-marked and 0.88 for double-marked candidates, compared with a projected reliability of 0.73 for the same 214 candidates taking the OSCE. CONCLUSION: If history-taking long cases are observed, three-and-a-half hours of testing time using 10 unstandardized patients would produce a reliable test. Long cases therefore are, in terms of reliability, no worse and no better than OSCEs in assessing clinical competence.

Clinical Competence↗

ALSPAC--the Avon Longitudinal Study of Parents and Children. I. Study methodology.

ALSPAC (The Avon Longitudinal Study of Parents and Children, formerly the Avon Longitudinal Study of Pregnancy and Childhood) was specifically designed to determine ways in which the individual's genotype combines with environmental pressures to influence health and development. To date, there are comprehensive data on approximately 10,000 children and their parents, from early pregnancy until the children are aged between 8 and 9. The study aims to continue to collect detailed data on the children as they go through puberty noting, in particular, changes in anthropometry, attitudes and behaviour, fitness and other cardiovascular risk factors, bone mineralisation, allergic symptoms and mental health. The study started early during pregnancy and collected very detailed data from the mother and her partner before the child was born. This not only provided accurate data on concurrent features, especially medication, symptoms, diet and lifestyle, attitudes and behaviour, social and environmental features, but was unbiased by parental knowledge of any problems that the child might develop. From the time of the child's birth many different aspects of the child's environment have been monitored and a wide range of phenotypic data collected. By virtue of being based in one geographic area, linkage to medical and educational records is relatively simple, and hands-on assessments of children and parents using local facilities has the advantage of high quality control. The comprehensiveness of the ALSPAC approach with a total population sample unselected by disease status, and the availability of parental genotypes, provides an adequate sample for statistical analysis and for avoiding spurious results. The study has an open policy in regard to collaboration within strict confidentiality rules.

Adult↗

Hepatocellular carcinoma and chemoembolization.

BACKGROUND: Chemoembolization is often used in the treatment of hepatocellular carcinoma; however, there are limited data on its efficacy in an Australian setting. AIMS: To review retrospectively the experience of 21 patients with hepatocellular carcinoma who collectively had 36 chemoembolizations performed between October 1995 and February 1999 in a teaching hospital and liver transplant centre in Victoria. METHODS: Selective catheterization of the right or left hepatic arteries was performed. A mixture of cisplatin 50 mg, epirubicin 50 mg, mitomycin C 10 mg, Lipiodol and gelfoam was injected. Computed tomography (CT) scans were performed at baseline and at 1-3 months after chemoembolization. Outcome measures included response rates, toxicity, progression-free and overall survival. RESULTS: CT response rates: partial response 19% (n = 7), median duration 11 months (range 2+ to 37+); minor response 17% (n = 6), median duration 7 months (1+ to 12+); stable disease 42% (n = 15), median duration 3 months (1+ to 15 months); and progressive disease 22% (n = 8). Major toxicities included one case each of acute renal failure, contrast encephalopathy, gastric ulceration and hepatorenal failure. Median progression-free survival was 3 months (range 0-37+). Median overall survival was 15 months (range 6-50+). CONCLUSION: Chemoembolization has a role in the palliative treatment of hepatocellular carcinoma. Our response rates and toxicity data are consistent with those in the published literature. However, new treatments are needed and prevention of disease by reduction in the prevalence of chronic hepatitis B and C will be required to significantly reduce mortality from this tumour.

Adult↗

Surveillance of antibiotic resistance in European ICUs.

Antibiotic resistance among bacteria causing hospital-acquired infections poses a threat, particularly to patients in intensive care units (ICUs). In order to control the spread of resistant bacteria, local, regional and national resistance surveillance data must be used to develop efficient intervention strategies. In an attempt to identify national differences and the dynamics of antibiotic resistance in European ICUs, data have been merged from several networks of resistance surveillance performed during the 1990s. It should be stressed, however, that comparisons of results from different studies using different methods and different population samples must be made with caution. Antibiotic resistance across all species and drugs was, with some exceptions, highest in southern European countries and Russia, and lowest in Scandinavia. More effective strategies are needed to control the selection and spread of resistant organisms. Antibiotic intervention policies, efficient infection control measures and an overall awareness of the serious implications at public health level will contribute to the management of antibiotic resistance.

Acinetobacter↗

Morphologic and mechanical characteristics of engineered bovine arteries.

OBJECTIVE: The ideal small-caliber arterial graft remains elusive despite several decades of intense research. A novel approach to the development of small-caliber arterial prostheses with a biomimetic system for in vitro vessel culture has recently been described. In this study we examined the effects of culture time and tissue culture scaffolding on engineered vessel morphology and function and found that these parameters greatly influence the function of engineered vessels. METHODS: This report describes the effects of culture time and scaffold type on vessel morphology, cellular differentiation, and vessel mechanical characteristics. Engineered vessels were cultured from bovine aortic smooth muscle cells (SMCs) and endothelial cells that were seeded onto biodegradable polymer scaffolds and cultured under physiologically pulsatile conditions. Engineered vessels were subjected to histologic, ultrastructural, immunocytochemical, and mechanical analyses. RESULTS: Vessel morphology and mechanical characteristics improved as time in culture increased to 8 weeks. SMCs in the engineered vessel wall were organized into a highly lamellar structure, with cells separated by alternating layers of collagen fibrils. Polymer scaffold remnants were present in vessels cultured for 8 weeks, and SMCs that were in proximity to polymer remnants exhibited a dedifferentiated phenotype. CONCLUSIONS: These findings aid in the systematic understanding of the effects of in vitro parameters on engineered vessels and will be useful for the translation of vessel culture techniques to human cells for the development of autologous human vascular grafts.

Animals↗

Rat germinal cells require PARP for repair of DNA damage induced by gamma-irradiation and H2O2 treatment.

The ability of rat germinal cells to recover from genotoxic stress has been investigated using isolated populations of primary spermatocytes and round spermatids. Using a comet assay at pH 10.0 to assess single strand breakage (SSB) in DNA, it was found that a high level of damage was induced by 5 Gy gamma-irradiation and acute exposure to 50 microM H2O2. This damage was effectively repaired during a subsequent recovery period of 1-3 hours culture in vitro but repair was significantly delayed in the presence of the poly(ADP-ribose)polymerase (PARP) inhibitor 3-aminobenzamide (3-ABA). Immunofluorescence detection of PARP with specific antibodies localised the protein to discrete foci within the nucleus of both spermatocytes and spermatids. Poly(ADP-ribose) (pADPR) could also be detected in spermatid nuclei following gamma-irradiation or H2O2 treatment. Moreover, PARP activation occurs both in spermatocytes and spermatids left to recover after both genotoxic stresses. The NO donors, 3-morpholino-sydnonimine (SIN-1) and S-nitrosoglutathione (SNOG), caused significant SSBs in both spermatocytes and spermatids. The effects of SIN-1 could be prevented by exogenous catalase (CAT), but not superoxide dismutase (SOD), in the cell suspensions. SNOG-induced SSBs were insensitive to both CAT and SOD. It is concluded that DNA in spermatocytes and spermatids is sensitive to damage by gamma-irradiation and H2O2 and that efficient repair of SSBs requires PARP activity.

Animals↗