Search PubMed⌕ Search

Biomedical subjects

P Evans

Publications and source records attributed to P Evans.

At least 37 records · Page 2Linked to original sources
PubMed2002

Ultrasound measures of bone and the diurnal free cortisol cycle: a positive association with the awakening cortisol response in healthy premenopausal women.

In this study we examined the relationship between characteristics of the diurnal pattern of salivary free cortisol concentration and ultrasound (US) measures of bone in premenopausal women. Subjects were 36 healthy, eumenorrhoeic, nonsmoking women mean age (SE) 30.9 (1.3) years. Saliva samples were collected on awakening and 10, 20, 30, 120, 240, and 600 minutes thereafter. Calcaneal broadband ultrasonic attenuation (BUA) and speed of sound (SOS) were determined. Mean (SE) salivary cortisol concentration was 4.7 (0.5) nmol/l on awakening, peaked at 8.6 (0.9) nmol/l 30 min later, and declined to a trough of 2.3 (0.2) nmol/l 600 min after awakening. BUA and SOS were significantly associated with cortisol 0 and 30 min after awakening (r = 0.40 and 0.40 for BUA and 0.33 and 0.37 for SOS, respectively, with body mass included as covariate). Cortisol levels 240 and 600 min after awakening were not significantly associated with bone variables. Women above the median for peak (30 min after awakening) cortisol had significantly higher BUA and SOS than those below the median [BUA 51.8 (1.0) vs 47.4 (1.5) dB/MHz, P = 0.017; SOS 1554.0 (2.5) vs 1546.4 (1.5) m/sec, P = 0.008]. A high peak in cortisol following awakening was associated with higher US measures of bone in healthy premenopausal women. This finding suggests the possibility that diurnal variation in cortisol may have a role in bone metabolism.

Adult↗
PubMed2002

Mechanisms of magnesium-stimulated adhesion of osteoblastic cells to commonly used orthopaedic implants.

Poor cell adhesion to orthopaedic and dental implants may result in implant failure. Cellular adhesion to biomaterial surfaces primarily is mediated by integrins, which act as signal transduction and adhesion proteins. Because integrin function depends on divalent cations, we investigated the effect of magnesium ions modified bioceramic substrata (Al(2)O(3)-Mg(2+)) on human bone-derived cell (HBDC) adhesion, integrin expression, and activation of intracellular signalling molecules. Immunohistochemistry, flow cytometry, cell adhesion, cell adhesion blocking, and Western blotting assays were used. Our findings demonstrated that adhesion of HBDC to Al(2)O(3)-Mg(2+) was increased compared to on the Mg(2+)-free Al(2)O(3). Furthermore, HBDC adhesion decreased significantly when the fibronectin receptor alpha5beta1- and beta1-integrins were blocked by functional blocking antibodies. HBDC grown on the Mg(2+)-modified bioceramic expressed significantly enhanced levels of beta1-, alpha5beta1-, and alpha3beta1-integrins receptors compared to those grown on the native unmodified Al(2)O(3). Tyrosine phosphorylation of intracellular integrin-dependent signalling proteins as well as the expression of key signalling protein Shc isoforms (p46, p52, p66), focal adhesion kinase, and extracellular matrix protein collagen type I were significantly enhanced when HBDC were grown on Al(2)O(3)-Mg(2+) compared to the native Al(2)O(3). We conclude that cell adhesion to biomaterial surfaces is probably mediated by alpha5beta1- and beta1-integrin. Cation-promoted cell adhesion depends on 5beta1- and beta1-integrins associated signal transduction pathways involving the key signalling protein Shc and results also in enhanced gene expression of extracellular matrix proteins. Therefore, Mg(2+) supplementation of bioceramic substrata may be a promising way to improve integration of implants in orthopaedic and dental surgery.

Aluminum Oxide↗
PubMed2002

Local lymph node assay - validation, conduct and use in practice.

The validation of alternative methods is a relatively new activity in toxicology. The local lymph node assay (LLNA), a novel method for the identification of chemicals that have the potential to cause skin sensitization, was the first test to pass through the formal regulatory validation process established in the USA under the auspices of ICCVAM, the Interagency Coordinating Committee on the Validation of Alternative Methods. ICCVAM approved the LLNA as an alternative to guinea pig tests for the identification of skin sensitisation hazards. In this report, we explore the nine recommendations made by ICCVAM and discuss their interpretation in relation to the new OECD Guideline 429, which describes the LLNA. In particular, the value and limitations of the use of statistical evaluation of data and of the inclusion of routine positive controls is examined. It is concluded that the OECD Guideline as currently written embodies the necessary flexibility to permit conduct of the LLNA in a manner necessary to meet the varying needs of regulatory agencies and toxicologists around the world.

Animals↗
PubMed2001

Recognition of E-cadherin by integrin alpha(E)beta(7): requirement for cadherin dimerization and implications for cadherin and integrin function.

We have investigated the importance of dimerization of E-cadherin in the heterophilic adhesive interaction between E-cadherin and integrin alpha(E)beta(7). Dimerization of cadherin molecules in parallel alignment is known to be essential for homophilic adhesion and has been attributed to Ca(2+)-dependent interactions in the domain 1-2 junction or to cross-intercalation of Trp2 from one molecule to the other. We have disrupted either or both of these proposed mechanisms by point mutations in E-cadherin-Fc and have tested the modified proteins for alpha(E)beta(7)-mediated cell adhesion. Prevention of Trp2 intercalation had no adverse effect on integrin-mediated adhesion, whereas disruption of Ca(2+) binding permitted adhesion but with reduced efficiency. Both modifications in combination abolished recognition by alpha(E)beta(7). In EGTA, alpha(E)beta(7) adhered to wild type E-cadherin but not to the Trp2 deletion mutant. Independent evidence that the mutations prevented either or both mechanisms for dimerization is presented. The data show that dimerization is required for recognition by alpha(E)beta(7) and that it can take place by either of two mechanisms. Implications for the roles of the alpha(E) and beta(7) integrin subunits in ligand binding and for Trp2 and Ca(2+) in the assembly of cadherin complexes are discussed.

Animals↗
PubMed2001

Ultrafast source-to-surface movement of melt at island arcs from 226Ra-230Th systematics.

Island arc lavas have radium-226 excesses that extend to higher values than those observed in mid-ocean ridge or ocean island basalts. The initial ratio of radium-226 to thorium-230 is largest in the most primitive lavas, which also have the highest barium/thorium ratios, and decreases with increasing magmatic differentiation. Therefore, the radium-226 excesses appear to have been introduced into the base of the mantle melting column by fluids released from the subducting plate. Preservation of this signal requires transport to the surface arguably in only a few hundreds of years and directly constrains the average melt velocity to the order of 1000 meters per year. Thus, melt segregation and channel formation can occur rapidly in the mantle.

Journal Article↗
PubMed2001

Exploration of the awakening cortisol response in relation to diurnal cortisol secretory activity.

Adrenocortical activity can be assessed by measurement of free cortisol in saliva. Cortisol status has important health implications in both physical and psychological terms. Assessment of cortisol status is complicated by the marked diurnal cortisol cycle. This cycle is characterised by an increase in secretory activity following awakening to achieve the morning acrophase. Thereafter it falls with a declining trend over the remainder of the day. For between subject studies the timing of sampling in relation to this cycle is an important consideration. We report a comprehensive study of the diurnal free cortisol cycle designed to analyse its components and to investigate their reliability and inter-relatedness. We instructed 42 healthy volunteers to collect saliva samples at home on two consecutive days. On each day the first sample was collected immediately upon awakening, followed by a further three samples at 15-minute intervals which collectively comprised the "awakening samples". A further four sample's were collected through the day at 3-hour intervals, all synchronized to awakening time. The cortisol response to awakening was calculated in two ways. Overall cortisol production in the first 45 minutes after awakening was calculated as area under the cortisol curve with reference to zero (AUC). The dynamic of the cortisol response to awakening was calculated as area under the cortisol response curve (AURC) with reference to the first awakening sample. In addition the underlying cortisol secretory activity was assessed based upon the diurnal three-hourly samples. All three parameters of adrenocortical activity showed reasonable stability across the two sampling days indicating all were reliable indexes of trait characteristic. AUC was representative of underlying diurnal activity but AURC was not. Measurement at any time point, 3, 6, 9 or 12 hours post-awakening was representative of the underlying 12-hour diurnal activity.

Adrenal Cortex↗
PubMed2001

Association between time of awakening and diurnal cortisol secretory activity.

A 12-hour diurnal profile of salivary free cortisol was measured in healthy adults (n=40) on two consecutive days. Samples were collected at timed intervals synchronised to awakening. The mean profile is characterised by a marked increase in cortisol concentration following awakening, peaking after about 30 min, and a subsequent decline over the remainder of the day. Thus two components of the diurnal cycle were examined: a) the first 45 min post-awakening (the awakening cortisol response) and b) the underlying 12 h profile from immediately until 12 h post awakening (but without the awakening response). Both of these components were analysed in two ways such as to provide an indication of overall cortisol concentration and the degree of change in cortisol concentration, i.e. the rise for the awakening response and the diurnal decline. Both components of the cortisol diurnal profile were negatively correlated with awakening time. Thus, those subjects who awoke earliest had higher levels of cortisol over the 45 min following awakening as well as throughout the rest of the day. They also displayed a more marked diurnal decline to be convergent with late awakeners at the end of diurnal measurement, 12 h following awakening. Hence the diurnal cortisol cycle, which is synchronised to awakening, is significantly related to awakening time. These findings support the notion of a close association between suprachiasmatic nucleus (SCN) control of both awakening and cortisol secretory activity.

Adult↗
PubMed2001

High resolution ID-ICP-MS certification of an estuary water reference material (LGC 6016) and analysis of matrix induced polyatomic interferences.

Reliable trace metal analysis of environmental samples is dependent upon the availability of high accuracy, matrix reference standards. Here, we present Cd, Cu, Ni, Pb and Zn isotope dilution determination for an estuary water certified reference material (LGC 6016). This work highlights the need for high-accuracy techniques in the development of trace element CRMs rather than conventional inter-laboratory trials. Certification of the estuary water LGC6016 was initially determined from a consensus mean from 14 laboratories but this was found to be unsatisfactory due to the large discrepancies in the reported concentrations. The material was re-analysed using isotope dilution ICP-MS techniques. Pb and Cd were determined using a conventional quadrupole ICP-MS (Elan 5000). Cu, Zn and Ni were determined using a magnetic sector ICP-MS (Finnigan Element), which allowed significant polyatomic interferences to be overcome. Using the magnetic sector instrument, precise mass calibration to within 0.02 amu permitted identification of the interferences. Most interferences derived from the sample matrix. For example, the high Na content causes interferences on 63Cu, due to the formation of 40Ar23Na and 23Na2 16O1H, which in a conventional quadrupole instrument would relate to an erroneous increase in signal intensity by up to 20%. For each analyte a combined uncertainty calculation was performed following the Eurachem/GTAC and ISO guideline. For each element a combined uncertainty of 2-3% was found, which represents a 10-fold improvement compared to certification by inter-laboratory comparison. Analysis of the combined uncertainty budget indicates that the majority of systematic uncertainty derives from the instrumental isotope ratio measurements.

Calibration↗
PubMed2001

In-vitro activity of S. lavandulaefolia (Spanish sage) relevant to treatment of Alzheimer's disease.

Salvia lavandulaefolia Vahl. (Spanish sage) essential oil and individual monoterpenoid constituents have been shown to inhibit the enzyme acetylcholinesterase in-vitro and in-vivo. This activity is relevant to the treatment of Alzheimer's disease, since anticholinesterase drugs are currently the only drugs available to treat Alzheimer's disease. Other activities relevant to Alzheimer's disease include antioxidant, anti-inflammatory and estrogenic effects. Results of in-vitro tests for these activities are reported here for S. lavandulaefolia extracts, the essential oil and its major constituents. Antioxidant activity (inhibition of bovine brain liposome peroxidation) was found in the EtOH extract of the dried herb (5 mg mL(-1)) and the monoterpenoids (0.1 M) alpha- and beta-pinene and 1,8-cineole. Thujone and geraniol had lower antioxidant effects, while camphor had no antioxidant effects. Possible anti-inflammatory activity (eicosanoid inhibition in rat leucocytes) was found in the EtOH extract (50 microg mL(-1)) and was shown by the monoterpenoids alpha-pinene and geraniol (0.2 mM), but not 1,8-cineole, thujone or camphor. Possible estrogenic activity (via induction of beta-galactosidase activity in yeast cells) was found in the essential oil (0.01 mg mL(-1)) and the monoterpenoid geraniol (0.1-2 mM). 1,8-Cineole, alpha- and beta-pinene and thujone did not exhibit estrogenic activity in this analysis. These results demonstrate that S. lavandulaefolia, its essential oil and some chemical constituents have properties relevant to the treatment of Alzheimer's disease and provide further data supporting the value of carrying out clinical studies in patients with Alzheimer's disease using this plant species.

Alzheimer Disease↗
PubMed2001

Micronutrients: oxidant/antioxidant status.

Potentially damaging species (reactive oxygen, nitrogen and chlorine species) arise as by-products of metabolism and as physiological mediators and signalling molecules. Levels of these species are controlled by the antioxidant defence system. Several components of this system are micronutrients (e.g. vitamins C and E) or are dependent upon dietary micronutrients (e.g. CuZn and Mn superoxide dismutase). The antioxidant defences act as a coordinated system where deficiencies in one component may affect the efficiency of the others. Oxidative stress may be an important factor in infection if micronutrients are deficient.

Antioxidants↗
PubMed2001

End-of-life decisions: physicians as advocates for advance directives.

Physicians have a unique role in supporting patients and families throughout their lives; their expertise is called on not only in life, but also at its end. This study was designed to determine the effect of an individual's age, gender, and attachment to the decision maker with regard to life support choices. A total of 151 subjects completed the researcher-developed instrument. Results suggest that the age of patients is significantly related to the life support options chosen. Specifically, the greater the age of the patient, the more likely a less vigorous life support alternative was chosen. Gender and attachment had no effect on the level of care chosen. Study participants also identified reasons for selecting a particular life support choice for each case. The most common reasons given for a close relative centered around quality-of-life issues. In situations involving a nonrelative, life support decisions were likely to be made using the principle of best interest. The primary care physician has a unique opportunity to initiate discussions about life support issues with patients and families. These decisions must be framed in the context of individual patient expectations and desires throughout the life span.

Adult↗
PubMed2000

Training primary care physicians to give limited manual therapy for low back pain: patient outcomes.

STUDY DESIGN: Randomized controlled study of standard manual therapy given by 31 generalist physicians to 295 patients, in primary care practice. OBJECTIVES: To determine whether training primary care physicians in techniques of limited manual therapy would result in improved outcomes for their patients with acute low back pain. SUMMARY OF BACKGROUND DATA: Controversy continues regarding the benefit of spinal manual therapy and the role of highly trained manual therapists in the care of low back pain. Continuing medical education in manual therapy is frequently offered to generalist physicians, but nothing is known of the value and effectiveness of this training. METHODS: Thirty-one primary care physicians were trained to provide optimal low back care (enhanced care) and a sequence of eight standard manual therapy techniques. Two hundred ninety-five patients were randomized into two treatment groups: enhanced care alone and enhanced care with manual therapy. Main outcome measures included the Roland-Morris functional disability scale measured over time and patient-reported time to functional recovery, time to complete recovery, and satisfaction with care. RESULTS: No differences were found in Roland-Morris scores over time, mean functional days to recovery, days absent from work, or patient satisfaction. More patients receiving manual therapy (21; 14%) had completely recovered after the first visit compared with the control group (8; 6%; P = 0.01). Patients who received more intense manual therapy (four or more maneuvers) had a more rapid return to functional recovery (7.8 days) compared with those who received less intense manual therapy (11.1 days; P = 0.02). CONCLUSION: Limited training in manual therapy techniques offers very modest benefit compared with high-quality (enhanced) care for acute low back pain. Outcomes may have been modified by failure of some participant physicians to undertake the required sequence of maneuvers. Intensity of manual therapy may be a factor in improving patient outcomes and needs further study.

Disability Evaluation↗