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Biomedical subjects

P Tucker

Publications and source records attributed to P Tucker.

At least 19 recordsLinked to original sources

Rest breaks and accident risk.

Regular rest breaks are recommended to prevent accumulation of accident risk during sustained activities. We examined the effect of rest breaks on temporal trends in industrial accident risk, by assessment of accident records from a large engineering company, obtained over 3 years. In 2 h of continuous work, relative risk of an accident in the last half-hour of a shift was 2.08 (95% CI 1.73-2.43) higher than in the first half-hour. Trends in risk did not seem to differ between three 2-h work periods. Regular rest breaks seem to be an effective way to control accumulation of risk during industrial shift-work.

Accidents, Occupational↗

Short-term effects on linear growth and bone turnover in children randomized to receive prednisolone or dexamethasone.

AIM: To compare the relative potency of prednisolone (Pred) and dexamethasone (Dex) on short-term growth and bone turnover. METHOD: Prospective study over 16 weeks of children randomized to receive Pred (40 mg/m2) or Dex (6.5 mg/m2) for the first 5 weeks as part of the MRC-ALL97/99 induction chemotherapy for acute lymphoblastic leukaemia (ALL). MEASUREMENTS: Lower leg length velocity (LLLV) and weight, serum IGF-I, serum bone alkaline phosphatase (bALP) levels and creatinine-adjusted, urinary excretion of deoxypyridinoline cross-links (DPD). SUBJECTS: Nineteen children (eight boys, 11 girls) with a median age of 5.9 years (range 2.6-13) and with a diagnosis of ALL. RESULTS: At week 2 of therapy, median LLLV in the Dex group was -1.5 mm/week (range 0.7 to -2.1) and significantly lower than the LLLV in the Pred group which was -0.1 mm/week (range 0.20 to -0.28; P < 0.05). In the Dex group, LLLV remained lower at week 8 (med LLLV, -0.3 mm/week, range 0 to -1.3) compared to LLLV in the Pred group at 0.3 mm/week (range 0.2-1.0; P < 0.05). Body weight showed an increase after week 2 and reached a peak in both groups of children at week 6. The change in weight from baseline was greater in the Dex group than the Pred group reaching a maximum change by week 5 of 17.5% (range 5-25) and 8.7% (range -3 to 18), respectively (P < 0.05). At presentation, median IGF-I level for the whole group was 83.5 micro g/l (range 31.8-293). IGF-I levels fell markedly during Dex therapy and continued to remain lower than baseline. At weeks 4, 6 and 8, median change in IGF-I from baseline was lower in the Dex group than the Pred group. From week 1 to week 3, median change in bALP was 72% (range -8 to 304) in the Pred group, whereas in the Dex group change in bALP was -1% (range 23 to -28; P < 0.005). By week 3, median bALP was higher in the Pred group at 65 U/l (range 36-187) than in the Dex group at 39 U/l (range 26-60; P < 0.05) but by week 6 median bALP in the Pred group had fallen to a similar level to the Dex group. At presentation, median DPD was 22 nmol/l (range 17-38) and 20 nmol/l (range 12-26) in the Pred and Dex groups, respectively (ns), reaching a nadir between weeks 3 and 6. The median percentage change in DPD in the Pred and Dex group from week 1 to week 3 was -34% (range -7 to 14) and -53% (range -6 to -69), respectively (ns). By week 8, DPD excretion had started to rise more dramatically in the Pred group such that the median DPD was 35 nmol/l (range 10-53) in the Pred group and 22 (range 9-30) in the Dex group (P < 0.05). On average, between weeks 2 and 8, LLLV was three times lower, percentage gain in weight was three times higher, bALP was 1.3 times lower and DPD was 1.5 times lower in the Dex group than the Pred group. CONCLUSION: Pred and Dex both affect short-term growth and bone turnover. The mechanism of the effect on bone formation may be different between the two drugs. Dex may be about 18 times more potent than Pred at suppressing short-term linear growth and stimulating weight gain, and about nine times more potent at suppressing bone turnover. Glucocorticoids have a variable effect on different parameters of growth and bone turnover and the intensity may depend on the steroid used.

Adolescent↗

Crystallization and preliminary X-ray analysis of Drosophila glutathione S-transferase-2.

The sigma-class glutathione S-transferase-2 (GST-2) from Drosophila melanogaster is predominantly found within the indirect flight muscles (IFMs), where it is bound to the 'heavy' subunit of the IFM thin filament troponin complex (Tn-H). An N-terminal extension found in GST-2 is unique within the sigma GST class and may be involved in its interaction with Tn-H or modulate its enzymatic function. The recombinant protein has been crystallized at room temperature using ammonium sulfate as precipitant. Synchrotron radiation was used to measure a complete native data set to 1.75 A resolution from flash-cooled crystals. The crystals belong to one of the trigonal space groups P3(1)21 or P3(2)21, with unit-cell parameters a = b = 89.7, c = 131.8 A. The self-rotation function is consistent with a GST-2 dimer in the asymmetric unit.

Animals↗

The eyeless mouse mutation (ey1) removes an alternative start codon from the Rx/rax homeobox gene.

The eyeless inbred mouse strain ZRDCT has long served as a spontaneous model for human anophthalmia and the evolutionary reduction of eyes that has occurred in some naturally blind mammals. ZRDCT mice have orbits but lack eyes and optic tracts and have hypothalamic abnormalities. Segregation data suggest that a small number of interacting genes are responsible, including at least one major recessive locus, ey1. Although predicted since the 1940s, these loci were never identified. We mapped ey1 to chromosome 18 using an F2 genome scan and there found a Met10-->Leu mutation in Rx/rax, a homeobox gene that is expressed in the anterior headfold, developing retina, pineal, and hypothalamus and is translated via a leaky scanning mechanism. The mutation affects a conserved AUG codon that functions as an alternative translation initiation site and consequently reduces the abundance of Rx protein. In contrast to a targeted Rx null allele, which causes anophthalmia, central nervous system defects, and neonatal death, the hypomorphic M10L allele is fully viable.

Alternative Splicing↗

A profile of recyclers making special trips to recycle.

The aims of the research were to: (1) establish a profile of 'special recyclers', i.e. those who make special trips by car to recycle their household waste; and (2) establish whether the environmental burden resulting from their activities presents a significant environmental problem than needs pro-active management. The research was undertaken through surveys of recyclers at supermarket recycling centres and at civic amenity sites in Glasgow and across Ayrshire in south-west Scotland. Twenty-two percent of civic amenity recyclers made special trips to recycle, whilst at supermarkets less than 10% made special journeys. Those making special journeys tended to make shorter journeys than those combining recycling with another activity. Special recyclers also tended, on average, to recycle more items and bring greater weights of recyclable material per trip. No demographic difference was found between the special recyclers and the 'non-specials'. The environmental impact of consumer journeys to recycle was estimated from the statistic: 'The total distance travelled by car by special recyclers/the total weight deposited by all recyclers'. For the sites of this survey, this statistic ranged in value from 9 km tonne-1 to 106 km tonne-1. The lowest impacts of 9 km tonne-1 were at a supermarket site in a small town with a predominantly local catchment. The highest impacts were at a civic amenity site, in a major town, also used by residents from satellite communities. Over 50% of special recyclers cited nearness as their prime reason for choosing a particular site, compared with 32% of non-specials. Although special recyclers in Ayrshire did appear to act reasonably responsibly (environmentally), their activities produced additional environmental burden. Simulation studies demonstrate that up to 34% reduction in this burden may be possible through encouraging longer intervals between recycling trips. Three quarters of the environmental burden was attributable to less than 5% of the overall recycling population.

Attitude↗

Traumatic grief in a convenience sample of victims seeking support services after a terrorist incident.

This report describes traumatic grief in 40 individuals who suffered losses in the 1995 bombing of the Alfred P. Murrah Federal Building in Oklahoma City. We administered a self-report instrument 6 months after the bombing to assess demographics; exposure; injury; retrospective report of initial emotional and physiological reaction; and current posttraumatic stress symptoms, grief, safety concerns, and functioning. A strong association was found between posttraumatic stress symptoms and grief. The relationship between grief and difficulty functioning was stronger at higher levels of posttraumatic stress than at lower levels. The results support the construct of traumatic grief and have important implications for the treatment of people exposed to large-scale traumatic events and for the training of mental health professionals.

Adult↗

Episodic evolution of pyrin in primates: human mutations recapitulate ancestral amino acid states.

Familial Mediterranean fever (FMF; MIM 249100) is an autosomal recessive disease characterized by recurrent attacks of fever with synovial, pleural or peritoneal inflammation. The disease is caused by mutations in the gene encoding the pyrin protein. Human population studies have revealed extremely high allele frequencies for several different pyrin mutations, leading to the conclusion that the mutant alleles confer a selective advantage. Here we examine the ret finger protein (rfp) domain (which contains most of the disease-causing mutations) of pyrin during primate evolution. Amino acids that cause human disease are often present as wild type in other species. This is true at positions 653 (a novel mutation), 680, 681, 726, 744 and 761. For several of these human mutations, the mutant represents the reappearance of an ancestral amino acid state. Examination of lineage-specific dN/dS ratios revealed a pattern consistent with the signature of episodic positive selection. Our data, together with previous human population studies, indicate that selective pressures may have caused functional evolution of pyrin in humans and other primates.

Amino Acid Sequence↗

Temperature profiles, and the effect of sleep on them, in relation to morningness-eveningness in healthy female subjects.

There were 15 healthy female subjects, differing in their position on the "morningness-eveningness" scale, studied for 7 consecutive days, first while living a sedentary lifestyle and sleeping between midnight and 08:00 and then while undergoing a "constant routine." Rectal temperature was measured at regular intervals throughout this time, and the results were subjected to cosinor analysis both before and after "purification" for the effects of physical activity. Results showed that there was a phase difference in the circadian rhythm of core temperature that was associated with the morningness score, with calculations that "morning types" would be phased earlier than "evening types" by up to about 3 h. This difference in phase (which was also statistically significant when the group was divided by a median split into a "morning group" and an "evening group") could not be attributed to effects of waking activity and existed in spite of the subjects keeping the same sleep-wake schedule. Moreover, it persisted when the subjects' data had been purified and when the data were obtained from the constant routine. That is, there was an endogenous component to this difference in phase of the core temperature. The morning group also showed a greater fall of core temperature during sleep; this was assessed in two ways, the main one being a comparison of constant routine and nychthemeral data sets after correction for any effects of activity. Even though the morning group was sleeping at a later phase of their circadian temperature rhythm than was the evening group, neither group showed a fall of temperature due to sleep that varied with time elapsed since the temperature acrophase. It is concluded that another factor that differs between morning and evening types is responsible for this difference.

Behavior↗

Paroxetine in the treatment of chronic posttraumatic stress disorder: results of a placebo-controlled, flexible-dosage trial.

BACKGROUND: The objective of this double-blind, placebo-controlled study was to investigate the efficacy and safety of paroxetine in outpatients with posttraumatic stress disorder (PTSD). METHOD: Male and female outpatients 18 years and older who met DSM-IV criteria for PTSD and had baseline scores of 50 or greater on the Clinician Administered PTSD Scale (CAPS-2) were randomly assigned to treatment with paroxetine (20-50 mg/day) or placebo for 12 weeks. The primary efficacy variables were the change from baseline to the 12-week endpoint in the CAPS-2 total score and the proportion of responders on the Clinical Global Impressions-Global Improvement scale (CGI-1). Additional key outcome measures were the change from baseline in the reexperiencing, avoidance/ numbing, and hyperarousal scores of the CAPS-2 and in the total scores of the Treatment Outcome PTSD Scale and the patient-rated Davidson Trauma Scale and Sheehan Disability Scale (SDS). Depressive symptoms were assessed with the Montgomery-Asberg Depression Rating Scale. The proportion of patients achieving response and remission was also determined. RESULTS: 307 patients constituted the intent-to-treat population. At week 12, compared with the placebo group (N = 156), the paroxetine group (N = 151) showed significantly greater reduction of PTSD symptoms on both of the primary and all of the secondary outcome measures. Significantly greater improvement on the CAPS-2 total score was observed for paroxetine compared with placebo from week 4 (p < .05), and significantly greater proportions of paroxetine-treated patients achieved response (p < .001) and remission (p = .008) by week 12. The improvement in PTSD symptoms was similar in male and female patients. Functional improvement at the study endpoint was significantly greater (p < .05) in the paroxetine group in all 3 domains of the SDS (work, social life, family life). Treatment with paroxetine was well tolerated, with the frequency and type of adverse events recorded for the paroxetine group corresponding to the known safety profile of this medication. CONCLUSION: Paroxetine in doses of 20 to 50 mg once daily is effective as a treatment for chronic PTSD. Improvement is obtained for all 3 symptom clusters (reexperiencing, avoidance/numbing, hyperarousal) and is associated with significant reduction in disability after 12 weeks of treatment.

Adolescent↗

A comprehensive approach to stress in primary care.

Stress is a precipitant of many physical and emotional problems that patients present to their primary care physicians. Hans Selye's classic General Adaptation Syndrome is described as it relates to the body's response to stress. Techniques for assessing stress are presented. Stress management techniques that primary care physicians can employ in the office include prescribing relaxation and exercise, cognitive restructuring, dealing with negative thoughts, and setting appropriate goals. Severe or prolonged stress warrants consideration of a diagnosis of a mental disorder, use of a psychotropic medications, or referral to a psychiatrist or other mental health provider.

Humans↗

Predictors of post-traumatic stress symptoms in Oklahoma City: exposure, social support, peri-traumatic responses.

Eighty-five adults seeking mental health assistance six months after the Oklahoma City bombing were assessed to determine which of three groups of variables (exposure, peri-traumatic responses, and social support) predicted development of post-traumatic stress disorder (PTSD) symptoms. Variables most highly associated with subsequent PTSD symptoms included having been injured (among exposure variables), feeling nervous or afraid (peri-traumatic responses), and responding that counseling helped (support variables). Combining primary predictors in the three areas, PTSD symptoms were more likely to occur in those reporting counseling to help and those feeling nervous or afraid at the time of the bombing. Implications of these findings are discussed for behavioral health administrators and clinicians planning service delivery to groups of victims seeking mental health intervention after terrorist attacks and other disasters.

Adult↗

A comparison of some different methods for purifying core temperature data from humans.

Nine healthy females were studied about the time of the spring equinox while living in student accommodations and aware of the passage of solar time. After 7 control days, during which a conventional lifestyle was lived under a 24h "constant routine," the subjects lived 17 x 27h "days" (9h sleep in the dark and 18h wake using domestic lighting, if required). Throughout the experiment, recordings of wrist activity and rectal (core) temperature were taken. The raw temperature data were assessed for phase and amplitude by cosinor analysis and another method, "crossover times," which does not assume that the data set is sinusoidal. Two different purification methods were used in attempts to remove the masking effects of sleep and activity from the core temperature record and so to measure more closely the endogenous component of this rhythm; these two methods were "purification by categories" and "purification by intercepts." The former method assumes that the endogenous component is a sinusoid, and that the masking effects can be estimated by putting activity into a number of bands or categories. The latter method assumes that a temperature that would correspond to complete inactivity can be estimated from measured temperatures by linear regression of these on activity and extrapolation to a temperature at zero activity. Three indices were calculated to assess the extent to which exogenous effects had been removed from the temperature data by these purification methods. These indices were the daily variation of phase about its median value; the ratio of this variation to the daily deviation of phase about midactivity; and the relationship between amplitude and the square of the deviation of phase from midactivity. In all cases, the index would decrease in size as the contribution of the exogenous component to a data set fell. The purification by categories approach was successful in proportion to the number of activity categories that was used, and as few as four categories produced a data set with significantly less masking than raw data. The method purification by intercepts was less successful unless the raw data had been "corrected" to reflect the direct effects of sleep that were independent of activity (a method to achieve this being produced). Use of this purification method with the corrected data then gave results that showed least exogenous influences. Both this method and the purification by categories method with 16 categories of activity gave evidence that the exogenous component no longer made a significant contribution to the purified data set. The results were not significantly influenced by assessing amplitude and phase of the circadian rhythm from crossover times rather than cosinor analysis. The relative merits of the different methods, as well as of other published methods, are compared briefly; it is concluded that several purification methods, of differing degrees of sophistication and ease of application to raw data, are of value in field studies and other circumstances in which constant routines are not possible or are ethically undesirable. It is also concluded that such methods are often somewhat limited insofar as they are based on pragmatic or biological, rather than mathematical, considerations, and so it is desirable to attempt to develop models based equally on mathematics and biology.

Body Temperature↗

Fluvoxamine reduces physiologic reactivity to trauma scripts in posttraumatic stress disorder.

This study assessed the effect of open-label fluvoxamine treatment for posttraumatic stress disorder (PTSD), depressive symptoms, and physiologic arousal to trauma cues. Baseline psychometric ratings and physiologic assessments of heart rate and blood pressure responses to individualized, taped trauma scripts were determined for 16 patients with PTSD and 16 mentally healthy age- and gender-matched control subjects exposed to at least 1 serious trauma. Patients with PTSD had greater autonomic reactivity than control subjects at baseline, with physiologic measures correlating with the severity of the PTSD for the combined groups. Discriminant analyses indicated that systolic blood pressure best classified patients with PTSD (75% sensitivity) and control subjects (100% specificity), with a stepwise discriminant analysis showing that combined physiologic variables correctly classified 75% of patients with PTSD and 100% of control subjects. After 10 weeks of fluvoxamine treatment (100-300 mg/day), patients' PTSD, depression, and physiologic reactivity improved significantly. Medicated patients with PTSD could not be distinguished statistically from untreated control subjects in any physiologic measure. This dampening of autonomic reactivity after drug treatment corroborates subjective measures of improvement, validating the reported efficacy of fluvoxamine in this open trial.

Adult↗

Effects of direction of rotation in continuous and discontinuous 8 hour shift systems.

OBJECTIVES: Previous research has produced conflicting evidence on the relative merits of advancing and delaying shift systems. The current study assessed the effects of the direction of shift rotation within 8 hour systems, upon a range of measures including sleep, on shift alertness, physical health, and psychological wellbeing. METHODS: An abridged version of the standard shiftwork index which included retrospective alertness ratings was completed by four groups of industrial shiftworkers on relatively rapidly rotating 8 hour systems (n=611). Two groups worked continuous systems that were either advancing or delaying; the other two groups worked discontinuous systems that were either advancing or delaying. RESULTS: Few effects were found of direction of rotation on chronic measures of health and wellbeing, even when the systems incorporated "quick returns" (a break of only 8 hours when changing from one shift to another). This was despite the use of measures previously shown to be sensitive to the effects of a broad range of features of shift systems. However, advancing continuous systems seemed to be associated with marginally steeper declines in alertness across the shift (F (3,1080)=2.87, p<0.05). They were also associated with shorter sleeps between morning shifts (F (1,404)=4.01, p<0.05), but longer sleeps between afternoons (F (1,424)=4.16, p<0.05). CONCLUSIONS: The absence of negative effects of advancing shifts upon the chronic outcome measures accorded with previous evidence that advancing shifts may not be as harmful as early research indicated. However, this interpretation is tempered by the possibility that difficult shift systems self select those workers most able to cope with their deleterious effects. The presence of quick returns in advancing continuous systems seemed to impact upon some of the acute measures such as duration of sleep, although the associated effects on alertness seemed to be marginal.

Adult↗

Measurement and definition for smoking cessation intervention research: the smoke-free families experience. Smoke-Free Families Common Evaluation Measures for Pregnancy and Smoking Cessation Projects Working Group.

The measures, definitions, and processes used in the Smoke-Free Families clinical trials to assure consistent measurement and reporting of various aspects of the trials are described. Definitions of current smokers at different points in the pregnancy, levels of addiction, biological verification, cessation, stages of change, and intervention approaches are presented along with the rationale underlying their adoption and development.

Family↗

The changing incidence and spectrum of thyroid carcinoma in Tasmania (1978-1998) during a transition from iodine sufficiency to iodine deficiency.

Exposure to ionizing radiation, changing levels of iodine nutrition, and increased pathologic diagnosis of clinically unimportant thyroid neoplasia have all been proposed as explanations for a worldwide rise in the incidence of thyroid carcinoma (TC) over the past 6 decades. Tasmania is geographically an area of endemic iodine deficiency. In this report, we describe the spectrum of TC in a population averaging 450,000 persons during a 21-yr period that spans the communities transition from iodine sufficiency to iodine deficiency after discontinuation of universal iodine prophylaxis in the mid 1980s. The Tasmanian Cancer Register was used to ascertain all cases of TC diagnosed in Tasmania between 1978 and 1998. Histopathological and demographic data were reviewed. A total of 289 cases of TC were identified. Papillary TC (PTC), follicular TC, medullary TC, and other species accounted for 62%, 23%, 4%, and 11% of cases, respectively. The age standardized incidence rate for total TC increased from 2.45 to 5.33 per 100,000 for females and 0.75 to 1.76 per 100,000 for males between 1978 and 1984 and 1992 and 1998, respectively. A rise in the incidence of PTC by 4.5-fold (P < 0.05) in females and 2.1-fold in males (not significant) was the dominant change over this period. In parallel, the proportion of follicular TC relative to PTC fell from 0.35 to 0.17 during these years (P < 0.05). The rise in PTC incidence was, in part, due to an increase in the occurrence of tumors 1cm or less in diameter. Nonetheless, a 3-fold rise in incidence of larger lesions was also observed during the study period. Forty-three (24%) PTC cases had multifocal disease, 17 (40%) of whom had bilateral tumors. Familial (autosomal dominant) PTC was identified in nine (5%) total PTC cases. Prior studies have linked iodine prophylaxis to a rise in the proportion of differentiated TC, particularly PTC. Our data suggest a complex relationship between iodine nutrition and thyroid tumorigenesis. Factors such as a long latency between changes in iodine nutrition and thyroid tumorigenesis, a dose threshold for the effect of iodine nutrition on thyroid tumorigenesis, and an interaction between iodine nutrition and thyroidal sensitivity to ionizing radiation may all play a role.

Adenocarcinoma, Follicular↗

Diurnal variations in the mood and performance of highly practised young women living under strictly controlled conditions.

The diurnal variation in a range of psychological functions and core body temperature were investigated in a series of studies involving a total of 24 highly practised young women who lived in a controlled environment and on a strictly regimented 24-hour routine for 6 or 7 days. Ten participants were exposed to the natural light/dark cycle (L/Dc) through windows, whereas the 14 remaining participants saw no daylight, but all had access to normal clock time. A battery of mood and performance tests was completed every 2 hours whilst awake (08:00-00:00), resulting in nine equally spaced measures per waking day. Average time of day (ToD) functions were calculated from the last 5 or 6 days spent in the controlled environment. Significant ToD effects were found for many of the variables taken although the nature of these effects differed across measures, with a 'post-lunch dip' being observed at 16:00 in some variables. Analysis of the standardized data established that all variables presented reliably different ToD functions to core body temperature, whilst factor analyses indicated possible relationships between the variables. It was concluded that those variables that exhibited diurnal variation showed trends that did not parallel those in core body temperature.

Adult↗