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P Evans

Publications and source records attributed to P Evans.

At least 19 recordsLinked to original sources
PubMed2006

Suspected non-adherence and weekend versus week day differences in the awakening cortisol response.

The pronounced rise in cortisol following awakening holds promise as a bio-marker of variables in the psychosocial domain, but its investigation also presents methodological challenges, which we attempted to address in this study. Forty-eight healthy, young students participated and were instructed to collect saliva 0, 15, 30 and 45 min post awakening on two consecutive normal weekdays and two consecutive weekend days (order counterbalanced). Participants' awakening cortisol response (ACR) profiles differed between the weekdays and weekend with trend analysis revealing a steeper rise on weekdays compared to the weekend. These differences were not accounted for by weekday/weekend differences in awakening time and state stress or by perceived stress over the previous month. Total salivary-free cortisol secretion (area under the cortisol curve (AUC)) over the 4 study days was negatively correlated with the measure of longer term stress and awakening time. The mean 4-day rise in cortisol (mean increase: MnInc) was also negatively correlated with awakening time. This awakening time effect was not mediated by stress or vice versa, since both were independent predictors of cortisol. In an attempt to address the ubiquitous problem of non-adherence to the requested saliva sampling regime, known to distort the shape of the ACR, suspected non-adherence (SNA) was examined by identifying instances of profiles showing no cortisol rise from the waking sample to either the 15 or 30 min sample post awakening. Analysis controlling for SNA status had no effect upon the observed associations with Perceived Stress Scale (PSS) and awakening time however it abolished the otherwise highly significant flatter profile at weekends.

Adolescent↗
PubMed2006

The local lymph node assay in practice: a current regulatory perspective.

Following the formal acceptance of the local lymph node assay (LLNA) as an Organization for Economic Cooperation and Development (OECD) guideline in April 2002, the UK Health and Safety Executive (HSE) informed notifiers that this was now the method of choice for the assessment of skin sensitization potential under the EU notification scheme for new industrial chemicals (NONS). This paper summarizes the experience of the HSE for the 2-year period immediately following the issuing of this statement, during which 48 LLNA study reports were assessed for notification purposes. The issues discussed here include adherence to the OECD guideline, interpretation of results, and classification outcomes. Generally, notifying laboratories followed the OECD guideline successfully, with regard to the sex/ strain/numbers of mice used, the precise process used for measurement of cell proliferation, and the use of recommended vehicles and positive controls. Initially, use of the individual animal approach (measuring the cell proliferation in each animal rather than for a pooled dose group) highlighted problems caused by technical inexperience, but these were overcome by practice. Toxicity or irritation were found to be minor factors in dose selection; more important was the choice of vehicle to correctly maximize the test substance concentration, while maintaining appropriate application properties. Contrary to concerns that the LLNA would prove to be less sensitive or more sensitive than the traditionally used Guinea Pig Maximization Test (GPMT), the proportion of new substances classified as skin sensitizers was within the range observed in previous years. Although the sample size is relatively small, the experience of the HSE indicates that the LLNA is satisfactory for routine regulatory use.

Animals↗
PubMed2005

Post-awakening cortisol secretion during basic military training.

Salivary free cortisol concentrations in the first 30 min after awakening were assessed in 12 healthy army recruits at the beginning, middle and end of an 11-week intensive physical training course. To ensure strict adherence to protocol saliva collection was supervised and collected on each sampling day immediately on waking and again 15 and 30 min later. Self-rated psychological assessments of state levels of stress, arousal and fatigue were performed in the evening of each sampling day. A within-subjects repeated-measures analysis of participants who completed the course (12 of the original 20) showed a significant main effect of cortisol concentration across all three sampling points after awakening (F((2,22))=54.516, p<0.0001) and a significant main effect of weeks into the training course (F((3,33))=4.390, p=0.010). Further analysis of this effect of measurement-week revealed that at weeks 3 and 6 total cortisol secretion estimated by area under the curve was lower (F((3,33))=4.602, p=0.008) compared to the beginning and end of the course. Surprisingly self-reported stress, arousal and fatigue did not differ significantly across weeks, despite the large dropout rate (40%) and self-evident pressures of the course. We conclude that when controlling for many confounding variables, including participant adherence, post-awakening cortisol levels are sensitive to stressful challenge over a period of weeks.

Adolescent↗
PubMed2005

The diurnal patterns of the adrenal steroids cortisol and dehydroepiandrosterone (DHEA) in relation to awakening.

The steroid hormones, cortisol and dehydroepiandrosterone (DHEA) are the two main peripheral secretory products of the hypothalamic-pituitary-adrenal stress-neuroendocrine axis. The diurnal pattern of cortisol secretory activity has been well characterised. Various aspects of this pattern have been related to time of awakening, light exposure, psychological dimensions of affect, immune function and systemic health and well-being. DHEA is also an important adrenocortical steroid whose secretory activity has been related to immune function, psychological and health variables. The most pronounced feature of the diurnal cortisol cycle is a burst of secretory activity following awakening with a diurnal decline thereafter. We mapped DHEA secretory activity onto this cycle by measuring both steroids in saliva samples collected at distinct time points over the diurnal cycle, synchronised to awakening. Both steroids, particularly DHEA, showed stability across days of sample collection. A main distinction between cortisol and DHEA was that although DHEA was elevated in post-awakening samples compared with later in the day there was no evidence of an awakening stimulatory burst of DHEA secretory activity. Although DHEA in many respects paralleled cortisol secretory activity there was some dissociation; mean levels were positively but not tightly correlated. The secretory pattern of DHEA is very stable whereas cortisol secretory activity seems more sensitive to day-to-day variability.

Adolescent↗
PubMed2005

Can we influence medical students' approaches to learning?

Students use three approaches to learning and studying: deep, surface and strategic. These are influenced by the learning environment. In response to the General Medical Council's report 'Tomorrow's Doctors', the second year of the medical course at the University of Edinburgh was changed to promote deep learning, with learning objectives constructed according to the SOLO taxonomy, learning methods such as problem-based learning and constructively aligned written assignments and examinations. The Approaches to Study Skills Inventory for Students (ASSIST) was used to evaluate the effect of these changes. Scores were highest for deep approaches and lowest for surface approaches and showed almost no change during the course. There are various possible explanations. The students already scored highly on deep approaches at the beginning of Year 2 and it may be difficult to increase the deep scores further, particularly over the relatively short period of the study. Alternatively, the effect of the changes in learning environment may not be strong enough to change entrenched approaches which have hitherto been successful.

Cohort Studies↗
PubMed2005

A comparison of intrathecal fentanyl and diamorphine as adjuncts in spinal anaesthesia for Caesarean section.

This randomised controlled trial examines the effects of fentanyl and diamorphine, alone and in combination, as adjuncts to spinal anaesthesia for Caesarean section. Ninety-nine women undergoing elective Caesarean section with spinal anaesthesia using 0.5% hyperbaric bupivacaine were randomly allocated to receive fentanyl 15 microg (F), diamorphine 0.25 mg (D), or fentanyl 15 microg plus diamorphine 0.25 mg (FD), intrathecally. All women received morphine via a patient controlled analgesia system after surgery. There was no significant difference between the groups in time to achieve a block, discomfort, ephedrine use, nausea and vomiting, pruritus and sedation during surgery. Significant differences were observed in morphine consumption 4, 8, 12 and 24 h after surgery between both F and D groups, and F and FD groups, and also at 2 h between F and FD groups. There was a significant difference in pruritus at 4 h between the F and FD group. Our results suggest that diamorphine alone provides optimum benefits during and after surgery, when used in combination with hyperbaric bupivacaine for Caesarean section.

Adjuvants, Anesthesia↗
PubMed2005

Recent insights into interactions of deferoxamine with cellular and plasma iron pools: Implications for clinical use.

Despite the availability of deferoxamine (DFO) for more than three decades, its rates of interaction with cellular iron pools in different tissues, and the effects of its pharmacokinetics on the interaction with plasma iron pools, remain incompletely understood. The positive charge of DFO, together with the negative resting potential in vertebrate cells, favors cellular uptake, whereas the low lipophilicity and high molecular weight counter this effect. The findings presented suggest a facilitated uptake of DFO into hepatocytes, being several hundred-fold faster than into red cells. Antibodies that selectively recognize ferrioxamine (FO) show that initial hepatocellular iron chelation is cytosolic, but later transposes to lysosomal and ultimately canalicular compartments. Strong FO staining is visible in myocytes within 4-8 h after commencing a subcutaneous DFO infusion, indicating effective chelation of myocyte iron. A methodology was developed to study the interaction of DFO and its metabolites with plasma iron pools by stabilizing DFO with aluminum ions, thereby preventing iron shuttling from non-transferrin-bound iron (NTBI) onto DFO after plasma collection. DFO removes only about a third of NTBI rapidly, and NTBI is rarely cleared completely. Increasing DFO dosing does not increase NTBI removal, but instead leads to a greater rebound in NTBI on cessation of intravenous infusion. Thus, intermittent infusions of high-dose DFO are less desirable than continuous infusions at low doses, particularly in high-risk patients. Here the benefits of continuous DFO on heart function occur before changes in T2*-visible storage iron, consistent with early removal of a toxic labile iron pool within myocytes.

Animals↗
PubMed2004

The P23T cataract mutation causes loss of solubility of folded gammaD-crystallin.

Mutations in the human gammaD-crystallin gene have been linked to several types of congenital cataracts. In particular, the Pro23 to Thr (P23T) mutation of human gammaD crystallin has been linked to cerulean, lamellar, coralliform, and fasciculiform congenital cataracts. We have expressed and purified wild-type human gammaD, P23T, and the Pro23 to Ser23 (P23S) mutant. Our measurements show that P23T is significantly less soluble than wild-type human gammaD, with P23S having an intermediate solubility. Using synchrotron radiation circular dichroism spectroscopy, we have determined that the P23T mutant has a slightly increased content of beta-sheet, which may be attributed to the extension of an edge beta-strand due to the substitution of Pro23 with a residue able to form hydrogen bonds. Neither of the point mutations appears to have reduced the thermal stability of the protein significantly, nor its resistance to guanidine hydrochloride-induced unfolding. These results suggest that insolubility, rather than loss of stability, is the primary basis for P23T congenital cataracts.

Amino Acid Sequence↗
PubMed2004

The effect of dawn simulation on the cortisol response to awakening in healthy participants.

Bright light exposure after awakening has been shown to elevate cortisol levels in healthy participants. The present study examined the effect of dawn simulation (a treatment for seasonal affective disorder) on the cortisol response to awakening and mood. Twelve healthy participants were supplied with a dawn simulator (The Natural Alarm Clock, Outside In, Cambridge Ltd), a bedside light that increases in intensity prior to awakening to approximately 250 lux over 30 mins when an audible alarm sounds. A counterbalanced study was performed on 4 consecutive normal weekdays, two of which were control days (no dawn simulation) and two experimental (dawn simulation). Saliva samples were taken immediately on awakening then at 15, 30 and 45 minutes post awakening on all 4 study-days. Total cortisol production during the first 45 mins after awakening was found to be significantly higher in the experimental condition than in the control condition. Participants also reported greater arousal in the experimental condition and there was a trend for an association between increased arousal and increased cortisol secretory activity under dawn simulation. This study provides supportive evidence for the role of light and the suprachiasmatic nucleus in the awakening cortisol response.

Adult↗
PubMed2004

The awakening cortisol response: methodological issues and significance.

The awakening cortisol response (ACR) is a discrete and distinctive part of the cortisol circadian cycle. In healthy adults salivary free cortisol concentrations increase by between 50 and 160% in the first 30 min immediately post-awakening (approximate average increase of 9 nmol/l, range 4-15 nmol/l, estimated to be equivalent to about three secretory episodes). However there are no agreed norms for the absolute concentrations of free cortisol in saliva either immediately post-awakening (range of 4.7-18.5 nmol/l) or 30 min post-awakening (range of 8.6-21.9 nmol/l). This review explores reasons for these discrepancies in normative data including confounding factors such as gender, age, awakening time, light and participant adherence. Although the physiological role of the ACR has not been clearly defined evidence is discussed that suggests it is under a distinct regulatory influence, different from the rest of the diurnal cortisol secretory cycle. Despite the difficulties associated with its measurement a range of studies have demonstrated an association between the ACR and psychosocial variables, stress and health. However it remains unclear whether positive affect and good health are consistently associated with larger or smaller awakening responses. It is early days in the search for the role and significance of the ACR. Its putative role in the regulation of physiological function across the day (e.g. the immune system) and its sensitivity to psychosocial variables make it a prime candidate as an intermediary linking mind and health.

Adrenal Cortex↗
PubMed2004

Fixed dose combinations for tuberculosis: Lessons learned from clinical, formulation and regulatory perspective.

Worldwide, tuberculosis (TB) remains one of the most important communicable diseases in terms of morbidity and mortality. Its control requires multi-drug therapy for at least six months, which could lead to patient non-compliance, failure of therapy and ultimately resulting in the emergence of drug resistance. Fixed dose combinations (FDCs) in TB therapy reduce the number of tablets to be consumed and thereby increase patient compliance with recommended treatment regimens. Thus, FDCs play a significant role in preventing the emergence of drug resistance and successful treatment. However, the quality of FDCs with respect to variable bioavailability and their registration requirements are major hurdles to their implementation in national TB control programs. It is anticipated that a large global market for FDCs will encourage large-scale production and increased competition, which in turn will result in FDCs at affordable prices. The Global Drug Facility (GDF), established by the World Health Organization (WHO), aims to ensure universal uninterrupted access to quality TB drugs for implementation of directly observed treatment short-course (DOTS) in resource-poor countries. In this program, four FDCs were accepted as the drugs of first choice because of their obvious advantages in controlling TB. This demands the necessity of addressing quality and registration requirements of FDCs systematically. In light of this current knowledge on anti-TB FDCs, their dosage, combinations, available clinical studies and the experiences with TB therapy has been discussed in this article, which should serve as lessons for selection of appropriate FDCs for other diseases such as malaria and AIDS.

Antitubercular Agents↗
PubMed2004

The Global TB Drug Facility: innovative global procurement.

The Global TB Drug Facility (GDF) is a new initiative to increase access to high quality tuberculosis drugs. The GDF, a project of the Global Partnership to Stop TB, is managed by its secretariat, in the World Health Organization (WHO), Geneva. It aims to provide tuberculosis drugs to treat up to 11.6 million patients over the next 5 years and to assist countries to reach the WHO global TB control targets by 2005. The GDF was launched on 24 March 2001. Six rounds of applications have been completed, with 46 countries and non-governmental organisations (NGOs) approved for support. The GDF is not a traditional procurement mechanism. It has adopted an innovative approach to the supply of drugs, by linking demand for drugs to supply and monitoring, using partners to provide services, using product packaging to simplify drug management and linking grants to TB programme performance. This paper describes the GDF operational procedures and experience gained so far. Key achievements to date are also outlined, including the creation of a flexible supply system to meet differing programme needs, rapid establishment of procedures, reduction in TB drug prices--a catalyst for DOTS expansion in countries, standardisation of products, and collaboration with partners. The GDF is flexible enough to meet the needs of countries with a TB burden. The GDF experience could be used as an example for global procurement of drugs and commodities for other diseases, such as HIV/AIDS and malaria. In the future it is likely that the GDF will expand to include second-line drugs and diagnostic materials for TB and could assist other partnerships to develop similar mechanisms and facilities to meet country needs.

Antitubercular Agents↗
PubMed2003

A rapid and accurate method for the determination of plutonium in food using magnetic sector ICP-MS with an ultra-sonic nebuliser and ion chromatography.

In the event of a nuclear incident it is essential that analytical information on the distribution and level of contamination is available. An ICP-MS method is described which can provide data on plutonium contamination in food within 3 h of sample receipt without compromising detection limits or accuracy relative to traditional counting methods. The method can also provide simultaneous determinations of americium and neptunium. Samples were prepared by HNO3 closed-vessel microwave digestion, evaporated to dryness and diluted into a mobile phase comprising 1.5 M HNO3 and 0.1 mM 2,6-pyridinedicarboxylic acid. A commercially available polystyrene-divinylbenzene ion chromatography column provides on-line separation of 239Pu and 238U reducing the impact of the 238U1H interference. Oxidation of the sample using H2O2 ensures all Pu is in the Pu(+4) state. The oxidation also displaces Np away from the solvent front by changing the oxidation state from Np(+3) to Np(+4) and produces the insoluble Am(+4) ion. Simultaneous Pu, Am and Np analyses therefore require omission of the oxidation stage and some loss of Pu data quality. Analyses were performed using a magnetic sector ICP-MS (Finnigan MAT Element). The sample is introduced to the plasma via an ultrasonic nebuliser-desolvation unit (Cetac USN 6000AT+). This combination achieves an instrumental sensitivity of 238U > 2 x 10(7) cps/ppb and removes hydrogen from the sample gas, which also inhibits the formation of 238U1H. The net effect of the improved sample introduction conditions is to achieve detection levels for Pu of 0.020 pg g(-1) (4.6 x 10(-2) Bq kg(-1)) which is significantly below 1/10th of the most stringent EU (European Union) legislation, currently 0.436 pg g(-1) (1 Bq kg(-1)) set for baby food. The new method was evaluated with a range of biological samples ranging from cabbage to milk and meat. Recovery of Pu agrees with published values (100% +/- 20%).

Chromatography, Ion Exchange↗
PubMed2002

The awakening cortisol response: no evidence for an influence of body posture.

It has recently been reported that the orthostatic challenge associated with postural change from sitting to an upright position is stimulatory to the hypothalamic-pituitary-adrenal axis as evidenced by increased salivary free cortisol. This stimulatory influence is potentially a confound for the many psychoneuroendocrine studies for which salivary free cortisol is the main dependent variable. This particularly relates to laboratory psychosocial stress procedures in which subjects are invited to stand in order to deliver public speech and the studies which have explored the cortisol response to awakening in which postural shift has not been controlled for. We therefore examined, in a balanced cross over design whether the awakening cortisol response was influenced by standing, shortly after awakening or remaining supine during the response study period. In addition and in the same subjects we measured the cardiovascular response and saliva cortisol response to the orthostatic challenge of shifting from a supine to a standing position later in the diurnal cortisol cycle. The expected cortisol response to awakening was demonstrated but there was no evidence that the postural shift, supine to standing, confounded the response. This same postural shift later in the day induced the expected increase in heart rate but cortisol simply followed the circadian decline. Under the conditions of the present study we found no evidence that the postural shift supine to standing could induce a cortisol secretory episode such as to contribute towards the awakening response.

Adult↗