Search PubMed⌕ Search

Biomedical subjects

P Murray

Publications and source records attributed to P Murray.

At least 37 records · Page 2Linked to original sources

Efficacy of atorvastatin in achieving National Cholesterol Education Program low-density lipoprotein targets in women with severe dyslipidemia and cardiovascular disease or risk factors for cardiovascular disease: The Women's Atorvastatin Trial on Cholesterol (WATCH).

BACKGROUND: Recent studies have demonstrated that women at high risk for cardiovascular disease (CVD) benefit from cholesterol lowering to an extent similar to that of men. The ability to achieve established treatment goals for low-density lipoprotein cholesterol (LDL-C) in women with clearly defined risk factors has not been examined in detail. METHODS AND RESULTS: We have determined the efficacy and frequency of achieving target levels for LDL-C with atorvastatin on the basis of National Cholesterol Education Program Adult Treatment Panel II recommendations in 318 women according to the presence of CVD (198 women) or risk factors for CVD (120 women) and the presence of mixed dyslipidemia with obesity with or without CVD (72 women). Mean baseline LDL-C concentrations for women with established CVD were in the upper 10% of the distribution for age-matched North American women and, for those without CVD, were also extremely elevated and were in the top 5% of the LDL-C distribution for age-matched women in this population. The majority of participants without CVD (63%) reached LDL-C targets (LDL-C or=2 CVD risk factors) with 10 mg atorvastatin and 79% reached targets with up to 20 mg of atorvastatin. For women with established CVD, 34% achieved an LDL-C <or=100 mg/dL (2.6 mmol/L) with 10 mg and 60% reached this target with up to 20 mg of atorvastatin. With maximal titration to the LDL-C target, up to and including 80 mg atorvastatin, 87% of women without CVD and 80% of women with established CVD achieved LDL-C targets. The presence of mixed dyslipidemia with obesity did not affect the frequency of achieving LDL-C targets. CONCLUSION: Atorvastatin is very effective in achieving National Cholesterol Education Program Adult Treatment Panel II target concentrations for LDL-C in the majority of women with established CVD or CVD risk factors.

Adult↗

Assessment of osteoporosis using standard radiographs of the wrist.

BACKGROUND: This study evaluated the ability of the orthopaedic surgeon to radiographically assess bone density in the wrist with sufficient accuracy to determine which patients require treatment for osteoporosis. METHODS: Thirty-eight patients with unilateral distal radius fractures, 30 of whom were female, were included in this study. The mean age was 55 years (range 45 to 82). Standard radiographs of the fractured and normal wrists were taken. Dual energy x-ray absorptiometry was performed on the normal distal radius of all patients within 1 week of their injury. The radiographs were viewed in blinded randomized fashion on two separate occasions by three orthopaedic surgeons and once by a fourth. The participants were required to determine the presence of osteoporosis. Visual analog scales (VAS) were used to evaluate (1) porosity, (2) cortical thickness, (3) trabecular thickness, and (4) the number of trabeculae in the ultradistal radius. RESULTS: Intraobserver agreement assessing osteoporosis averaged 81% (kappa of 0.5393). VAS assessment was unreliable for all four parameters. Radiographic determination of osteoporosis had a specificity of 61% and a sensitivity of 61% using x-rays of the uninjured wrist. CONCLUSION: We conclude that orthopaedic surgeons cannot predict with sufficient accuracy using plain x-rays whether a patient is significantly osteoporotic.

Absorptiometry, Photon↗

Spindle cell conversion by Kaposi's sarcoma-associated herpesvirus: formation of colonies and plaques with mixed lytic and latent gene expression in infected primary dermal microvascular endothelial cell cultures.

Angiogenic Kaposi's sarcoma (KS) skin lesions found in both AIDS and non-AIDS patients are universally associated with infection by the presumed causative agent, known as KS-associated herpesvirus (KSHV) or human herpesvirus 8. KSHV genomes expressing latent state virus-encoded mRNAs and the LANA1 (latent nuclear antigen 1) protein are consistently present in spindle-like tumor cells that are thought to be of endothelial cell origin. Although the KSHV lytic cycle can be induced in rare latently infected primary effusion lymphoma (PEL) cell lines, the ability to transmit or assay infectious KSHV has so far eluded investigators. Here, we demonstrate that infection with supernatant virions derived from three different tetradecanoyl phorbol acetate-induced PEL cell lines can induce cultured primary human dermal microvascular endothelial cells (DMVEC) to form colonies of proliferating latently infected spindle-shaped cells, all of which express the KSHV-encoded LANA1 protein. Although their initial infectivity varied widely (JSC1 > > BC3 > BCP1), virions from all three cell lines produced distinctive spindle cell colonies and plaques without affecting the contact-inhibited cobblestone-like phenotype of adjacent uninfected DMVEC. Each infected culture could also be expanded into a completely spindloid persistently infected culture displaying aggregated swirls of spindle cells resembling those in KS lesions. Formation of new colonies and plaques was inhibited in the presence of phosphonoacetic acid or gangciclovir, but these antiherpesvirus agents had little effect on the propagation of already latently infected spindloid cultures. In persistently infected secondary cultures, patches of up to 10% of the spindloid cells constitutively expressed several early viral lytic cycle proteins, and 1 to 2% of the cells also formed typical herpesvirus DNA replication compartments, displayed cytopathic rounding effects, and expressed late viral antigens. We conclude that de novo KSHV infection induces a spindle cell conversion phenotype in primary DMVEC cultures that is directly associated with latent state expression of the LANA1 protein. However, these cultures also spontaneously reactivate to produce an unusual combination of both latent and productive but slow lytic cycle infection. The formation of spindle cell colonies and plaques in DMVEC cultures provides for the first time a quantitative assay for directly measuring the infectivity of KSHV virion preparations.

Antigens, Viral↗

General case quasi-pyramidal staff training to promote generalization of teaching skills in supervisory and direct-care staff.

The authors employed staff training strategies designed to enhance generalization of teaching skills in staff working with persons with developmental disabilities. Staff training consultants initially employed a general case training approach involving the use of specially selected client program exemplars to provide three supervisory staff with generalized teaching skills. Subsequently, supervisory staff used the general case approach to train teaching skills to direct-care staff, with staff training support from the consultants (quasi-pyramidal training). Supervisors showed improvement in teaching skills after supervisory staff training, but only one of the three supervisors exceeded 70% correct skill use. After participating in the training of their own staff, however, supervisors demonstrated further improvements in skill use. All direct-care staff showed improvement after quasi-pyramidal training, with seven of the nine staff exceeding 70% correct skill use. General case quasi-pyramidal training appears to have potential as a strategy for promoting generalization of staff teaching skills in both trainees and trainers.

Activities of Daily Living↗

Cognitive/behavioral treatment for sexual offenders: an examination of recidivism.

Recent research in the treatment of sexual offenders suggests that comprehensive cognitive/behavioral approaches may yield lower recidivism. This study reviewed such a program, existing in Jackson County, Oregon, since 1982. Offenders were mandated into this community-based program upon conviction of a felony or misdemeanor sexual offense, and averaged 2-3 years of participation. A group of offender who participated in the Jackson County program between 1985 and 1995 was identified through archival data from the Oregon Department of Corrections. The data revealed success or nonsuccess in treatment, and any new convictions for sexual or nonsexual offenses. A control group of nonsexual offenders in Jackson County, and a group of sexual offenders in Linn County who did not have access to any treatment program were also studied. As hypothesized, those Jackson County offenders who successfully completed treatment had lower recidivism rates than those who were unsuccessful in the program. The observed effect of the program was particularly strong for offenders who remained in treatment for 1 year or more. When review was restricted to those participants, the reoffense rate for Jackson County offenders was reduced by over 40% when compared with Linn County offenders.

Adult↗

Regulation of the differentiation and behaviour of extra-embryonic endodermal cells by basement membranes.

Both the extracellular matrix and parathyroid hormone-related peptide (PTHrP) have been implicated in the differentiation and migration of extra-embryonic endodermal cells in the pre-implantation mammalian blastocyst. In order to define the individual roles and interactions between these factors in endodermal differentiation, we have used embryoid bodies derived from Lamc1(-/-) embryonic stem cells that lack basement membranes. The results show that in the absence of basement membranes, increased numbers of both visceral and parietal endodermal cells differentiate, but they fail to form organised epithelia. Furthermore, although parietal endodermal cells only migrate away from control embryoid bodies in the presence of PTHrP, they readily migrate from Lamc1(-/-) embryoid bodies in the absence of PTHrP, and this migration is unaffected by PTHrP. Thus, the basement membrane between epiblast and extra-embryonic endoderm is required for the proper organisation of visceral and parietal endodermal cells and also restricts their differentiation to maintain the population of primitive endodermal stem cells. Moreover, this basement membrane inhibits migration of parietal endodermal cells, the role of PTHrP being to stimulate delamination of parietal endodermal cells from the basement membrane rather than promoting migration per se.

Animals↗

Oral vitamin C attenuates acute ischaemia-reperfusion injury in skeletal muscle.

Ischaemia-reperfusion injury (IRI) is caused by endothelial and subendothelial damage by neutrophil-derived oxidants. Vitamin C is an antioxidant which attenuates endothelial injury after IRI. Our aim was to evaluate the effect of oral vitamin C in the prevention of IRI in skeletal muscle. We used a model of cross-clamping (3 hours) and reperfusion (1 hour) of the cremaster muscle in rats. Muscle function was assessed electrophysiologically by electrical field stimulation. Infiltration by neutrophils was determined by the activity of tissue myeloperoxidase (MPO) and tissue oedema by the wet-to-dry ratio. Neutrophil respiratory burst activity was measured in control animals and groups pretreated with vitamin C. IRI significantly decreased muscle function and increased muscle neutrophil MPO activity and muscle oedema. Pretreatment with vitamin C preserved muscle function and reduced tissue oedema and neutrophil infiltration. Neutrophil respiratory burst activity was reduced in the group treated with vitamin C compared with the control group. We conclude that pretreatment with oral vitamin C protects against acute muscle IRI, possibly by attenuating neutrophil respiratory burst activity.

Acute Disease↗

How informed is consent? Use of an information booklet in patients undergoing total hip replacement.

For informed consent, patients must understand the risks and benefits of the proposed procedure. Fifty patients undergoing total hip replacement (THR) participated in an evaluation of a newly devised information booklet. Patients' understanding of the risks and benefits of THR was assessed using a questionnaire before and after they had read the booklet. Pre-booklet patients knew on average 2 benefits of THR, compared with 3 afterwards. Twenty-two patients initially identified no alternative treatment to THR. Those who knew an alternative stated on average 1 treatment compared with 2 in the post-booklet group. Fifteen patients identified no risks of THR initially, compared with two after reading the booklet. Initially patients reported 1 risk, versus 3 after reading the booklet. Forty-eight patients thought that the booklet increased their understanding of THR and its risks. Fourteen found it upsetting, but acceptable. Forty-six patients wished to keep the booklet.

Arthroplasty, Replacement, Hip↗

The porous coated anatomic total hip replacement. A ten to fourteen-year follow-up study of a cementless total hip arthroplasty.

BACKGROUND: We previously reported our two and five-year results of arthroplasty with the Porous Coated Anatomic total hip prosthesis. We now report on the performance of this prosthesis at ten to fourteen years. METHODS: The results of 311 total hip replacements in which a Porous Coated Anatomic prosthesis was inserted without cement in 279 patients were analyzed prospectively. The average age of the patients at the time of the replacement was sixty--one years (range, twenty to eighty-one years). Sixty-four patients (seventy-six hips) died postoperatively. Forty-five patients (forty-seven hips) were lost to follow-up, and four were excluded because of their medical condition. One hundred and sixty-eight patients (187 hips) were followed for ten to fourteen years (average, twelve years). Seventeen of those patients (seventeen hips) had a revision. RESULTS: The overall survival rate (with any revision as the end point) was 90.0% +/- 5.4% at fourteen years, with an average Harris hip score of 85 +/- 14 points. The prevalence of thigh pain was 36% (fifty-six of 157) in the late period (more than ten years postoperatively). Radiographs showed stable fixation, with bone ingrowth, of 83% (130) of the 156 acetabular components and 88% (137) of the 156 femoral components at the latest follow-up evaluation. Men had a significantly higher rate of femoral osteolysis than did women (p < 0.001). The rates of acetabular and femoral osteolysis associated with 32-mm femoral heads (49% [twenty-three] of forty-seven and 70% [thirty-three] of forty-seven, respectively) were significantly higher (p < 0.01) than those associated with 26-mm heads (26% [twenty-eight] of 109 and 30% [thirty-three] of 109, respectively). Despite this, revision (removal or exchange of components) was not directly related to head size; instead, it was related to polyethylene thickness. CONCLUSIONS: There have been persistent problems with the Porous Coated Anatomic hip system, including thigh pain and an increasing prevalence of osteolysis with time. Revision because of aseptic loosening was related more to the thickness of the polyethylene liner than to the size of the femoral head. Femoral heads with a 32-mm diameter did not increase the risk for revision provided that an adequate thickness of polyethylene had been used.

Adult↗

Regulation of programmed cell death by basement membranes in embryonic development.

The formation of the proamniotic cavity in the mammalian embryo is the earliest of many instances throughout development in which programmed cell death and the formation of epithelia play fundamental roles (Coucouvanis, E., and G.R. Martin. 1995. Cell. 83:279-287). To determine the role of the basement membrane (BM) in cavitation, we use embryoid bodies derived from mouse embryonic stem cells in which the LAMC1 genes have been inactivated to prevent BM deposition (Smyth, N., H.S. Vatansever, P. Murray, M. Meyer, C. Frie, M. Paulsson, and D. Edgar. 1999. J. Cell Biol. 144:151-610). We demonstrate here that LAMC1-/- embryoid bodies are unable to cavitate, and do not form an epiblast epithelium in the absence of a BM, although both embryonic ectodermal cells and extraembryonic endodermal cells do differentiate, as evidenced by the expression of cell-specific markers. Acceleration or rescue of BM deposition by exogenous laminin in wild-type or LAMC1-/- embryoid bodies, respectively, results in cavitation that is temporally and spatially associated with restoration of epiblast epithelial development. We conclude that the BM not only directly regulates development of epiblast epithelial cells, but also indirectly regulates the programmed cell death necessary for cavity formation.

Animals↗

Whiplash injury--are current head restraints doing their job?

It is generally accepted that the incidence of whiplash associated disorders is increasing in all industrialised countries, despite the almost universal fitment of head restraints in at least the front seats of cars. This is usually attributed to the fact that few people can be observed to follow the standard recommendations as regards head restraint positioning, that is, level with the head vertically and as close to the head as possible horizontally. This study set out to determine whether any other factors, in addition to head restraint adjustment, could be found which would influence the severity of whiplash injury. This was done by linking medical assessment of real-world accident victims with engineering assessment of the accident vehicles. A random sample of road accident victims suffering from whiplash associated disorder was studied. The vehicles they had been travelling in were examined to assess impact severity and, where possible, measurements were made of seat and head restraint adjustment with the subject sitting in the vehicle. All subjects were interviewed to assess the disability resulting from their injuries, and their progress was followed for 12 months. The results were subjected to statistical analysis to try to determine relationships between severity of injury (as measured by resultant disability) and a number of occupant- and vehicle-related factors. A significant proportion of the sample had suffered lumbar strain injury in addition to whiplash, and these were excluded from the present analysis. Frontal impact victims suffered symptoms indistinguishable from those of rear impact victims. The beneficial effects of good head restraint adjustment could not be clearly demonstrated, and some trends, especially in rear impacts, where the benefits of a well-adjusted restraint should have been very clear, indicated that larger distances from head to restraint were associated with lower disability. The paper discusses these counter-intuitive results and their implications.

Accidents, Traffic↗

Trace metal speciation and bioavailability in urban soils.

Urban soils often contain concentrations of trace metals that exceed regulatory levels. However, the threat posed by trace metals to human health and the environment is thought to be dependent on their speciation in the soil solution rather than the total concentration. Three inactive railway yards in Montréal, Québec, were sampled to investigate the speciation and bioavailability of Cd, Cu, Ni, Pb and Zn. Soil solutions were obtained by centrifuging saturated soil pastes. In the soil solutions, up to 59% of the dissolved Cd was in its free ionic form. For Cu, Pb and Zn, organic complexes were the predominant species. Over 40% of Ni was present as inorganic complexes if the solution pH exceeded 8.1. Multiple regression analyses showed that pH and total metals in soil were significantly correlated with the activities of free metal ions, except for Cd(2+), which only had a weak correlation with soil pH. Free, dissolved and total soil metals were tested for their ability to predict metal uptake by plants in the field. However, none of these metal pools were satisfactory predictors. The results indicated that in these urban soils, trace metals were mainly in stable forms and bioavailability was extremely low.

Journal Article↗

Evaluating three trace metal contaminated sites: a field and laboratory investigation.

Selecting guidelines to evaluate elevated metals in urban brownfields is hindered by the lack of information for these sites on ecosystem structure and function. A study was performed to compare three trace metal-contaminated sites in the metropolitan Montreal area. The goal was to obtain an idea of the organisms that may be present on urban brownfields and to measure if elevated metals alter the presence and activity of the indigenous biota. Field and laboratory studies were conducted using simple methodologies to determine the extent to which microbial activity affected by trace metal content, to assess diversity of plant and soil invertebrate communities and to measure phytoaccumulation of trace metals. It was found that microbial activity, as measured by substrate-induced respiration (SIR) and nitrification, was not affected by the levels of soil Cd, Cu, Ni, Pb and Zn recorded on the sites. Seven of the 12 invertebrate groups collected were sampled on soils with similar Cd, Cu, Ni, Pb and Zn concentrations. Diversity of plant species increased as a function of the length of time the sites had been inactive. Levels of metals in plant tissue were influenced by soil characteristics and not by total soil Cd, Cu, Ni, Pb and Zn.

Journal Article↗