A 38-year-old man with a 9 month history of neurological and cognitive impairment.
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Adult↗
Biomedical subjects
Peter Smith
Publications and source records attributed to Peter Smith.
In vitro antiplasmodial activity of abietane and totarane diterpenes isolated from Harpagophytum procumbens (devil's claw).
The development of drug resistance and resurgence of malaria has highlighted the need for new chemically diverse antimalarial drugs. This study investigates Harpagophytum procumbens DC. as a source of antiplasmodial hit compounds. The roots of wild harvested plants as well as the aerial sections, seeds and roots of cultivated H. procumbens were evaluated for in vitro antiplasmodial activity. Bioassay-guided fractionation of the petroleum ether root extract yielded two diterpenes, (+)-8,11,13-totaratriene-12,13-diol (1) and (+)-8,11,13-abietatrien-12-ol (2). Compounds 1 and 2 displayed significant (IC50 < 1 microg/mL) in vitro antiplasmodial activity against a chloroquine-resistant (K1) and -sensitive (D10) strain of Plasmodium falciparum, and low cytotoxicity (SI > 65) against two mammalian cell lines (CHO and HepG2). It was found that 1 and 2 did not modify the erythrocyte shape, which in conjunction with the cytotoxicity results, indicates selective antiplasmodial activity.
Animals↗
Social norms, social behaviours and health: an empirical examination of a model of social capital.
OBJECTIVE: To explore a model of social capital, specifically the association between socially oriented norms and behaviours and the effect that these factors have on the gradient between income and self-rated health across three different welfare states. METHOD: We used data from the 1995-97 World Values Survey, a cross-sectional study conducted in a variety of countries including Australia, United States, Sweden and Norway (n = 5,096). RESULTS: We found variation in the level of social capital measures across the three different welfare states. Socially oriented norms are not strongly correlated with each other, or with socially oriented behaviours. The presence of socially oriented norms or behaviours did not reduce the likelihood of lower income groups reporting poor self-rated health, relative to the highest income groups. CONCLUSIONS AND IMPLICATIONS: Many questions still exist regarding the relationship between social capital and health, including how to measure the social capital concept and whether and how social capital affects health, independent of material and economic conditions.
Altruism↗
The influence of health care organisations on health system performance.
OBJECTIVES: The governments of many countries are undertaking initiatives to assess the extent to which health care organisations fulfil important objectives of health care, such as health improvement, fair access and efficiency. However, the extent to which these health care organisations can influence these objectives is unclear. The purpose of this study is to examine the potential influence of English National Health Service territorial health authorities on 14 indicators of system performance. METHODS: The study uses performance data relating to approximately 5000 small geographical areas with average populations of 10,000. Multi-level statistical models are used to attribute variation in the indicators to three hierarchical levels--small areas, district health authorities and regional health authorities--after controlling for socio-demographic characteristics. Variations in indicators attributable to district or regional level give an indication of the extent to which health authorities may influence performance. RESULTS: After adjusting for socio-demographic characteristics, the proportion of variation in performance attributable to district health authorities varies from about 8% (for standardised mortality ratios) to about 76% (for waiting time for elective surgery). Variation at the regional level is smaller than at the district level. CONCLUSIONS: There appear to be very large variations between indicators in the extent to which health care organisations can influence health system performance. Choice of performance indicators and the managerial incentive regime based on the indicators should recognise this variability, as it is highly dysfunctional to hold managers accountable for measures of performance that are beyond their control.
Efficiency, Organizational↗
Predicting urine culture results by dipstick testing and phase contrast microscopy.
AIMS: Urine is the most frequently received clinical specimen for bacterial culture. To determine whether dipstick or microscopy results reliably predicted the presence or absence of a reportable urinary pathogen we performed dipstick testing and phase contrast microscopy on unspun urine from 500 specimens. We also investigated the relationship between the presence of squamous epithelial cells (SECs) and mixed growth on culture. METHODS: For each specimen, the presence of leukocyte esterase and urinary nitrite was recorded as well as the quantity of leukocytes (WBC), SECs, and erythrocytes. All cultures had the number and type of each organism recorded. Pyuria was defined as > or =10 WBC/mm(3). RESULTS: Specimens with <10 SEC/mm(3) had fewer isolates (0.9 isolate per culture) than specimens with > or =10 SEC/mm(3) (two isolates per culture); therefore, SEC contamination was defined as > or =10 SEC/mm(3). Of 500 specimens, 266 (53%) had no growth and 136 (27%) had mixed growth. A total of 288 (58%) specimens had negative dipstick results and completely normal microscopy. Of these, 11 (4%) had a pure growth of a urinary pathogen but the pathogen was present in only three (1%) at > or =10(5) CFU/mL. Of 413 urine specimens without SEC contamination, 323 (78%) had either no detectable growth or pure growth compared with only 41 of 87 (47%) with SEC contamination (P<0.001). Of the 413 urine specimens without SEC contamination, 90 (22%) had > or =2 organisms compared with 46 of 87 (53%) with contamination (P<0.01). Pyuria was present in only 21 of 266 (8%) urine specimens without growth but was present in 60 of 95 (64%) specimens containing a reportable pathogen (P<0.01). CONCLUSIONS: SEC contamination does not reliably predict cultures with mixed growth, urine specimens with negative dipstick results and microscopy rarely contain a reportable urinary pathogen, and screening algorithms are warranted and justified.
Adolescent↗
Knowledge, use of and attitudes towards peer support: a 2-year follow-up to the Prince's Trust survey.
This present study investigated how school peer support systems studied 2 years earlier in a survey funded by The Prince's Trust have evolved. In all, 413 pupils (actual and potential users of the systems) aged 13-14 (Year 9--Y9) and 15-16 (Year 11--Y11), 34 teachers in charge of systems and 80 peer supporters in 35 secondary schools were interviewed using structured schedules for the pupils and semi-structured ones for the teachers and peer supporters. All of these interviews focussed on the respondents' perceptions and experiences of the school's peer support system, including: the perceived benefits to users of the system; benefits to peer supporters; problems with the system and the attempts made to overcome them. There was widespread support for the systems and a strong sense that both teachers and peer supporters were increasingly confident about the value of their service. However, some problems remain, notably with regard to gender. The study documents difficulties in the recruitment and retention of boys as peer supporters because of peer pressure to conform to a "macho" image. The issue is discussed and some solutions presented.
Adolescent↗
Analysis of postural control synergies during quiet standing in healthy children and children with cerebral palsy.
OBJECTIVE: To estimate the contribution of body transverse rotation using weighted differential center of pressure signals during quiet standing in healthy children and in children with cerebral palsy. DESIGN: Body sway was indirectly measured through center of pressure data, which was calculated using dual force platforms. BACKGROUND: Assessment of postural control synergies using center of pressure data provides a unique method for center of mass data analysis in characterizing complex balance sway. METHODS: Using dual force platforms, linear expressions for the coordinates of right and left center of pressure signals were developed to identify and characterize balance control synergies during quiet standing. Subjects were also tested during eyes open and eyes closed trials to determine the significance of visual input on these control synergies. RESULTS: The limb protraction/retraction control was found to be dominant during medial-lateral sway, whereas the estimated body transverse rotation contribution was found to be more significant than the previously reported measures of anterior-posterior balance. These findings were consistent in healthy children and in children with cerebral palsy during both eyes open and eyes closed trials. CONCLUSION: The weighted differential center of pressure signals show that the estimated body transverse rotation contribution is significant in healthy children and critical for postural stability in children with cerebral palsy. RELEVANCE: This study identifies the significance of body transverse rotation control contribution in upright posture. Children with cerebral palsy with relatively poor ankle control demonstrate the importance of body transverse rotation for postural stability.
Ankle Joint↗
The role of the district nurse in bereavement support.
BACKGROUND: District nurses are frequently involved in the care of patients immediately prior to death and could therefore provide support to bereaved relatives. However, little is known about nurses' views on bereavement support or their actual involvement. AIMS OF THE STUDY: To survey a representative sample of district nurses to ascertain their current practice and perceived role in supporting bereaved people and to identify factors that influence their practice. DESIGN AND METHOD: A self-completed postal questionnaire was distributed anonymously to 522 district nurses in the central southern coastal area of Britain. It comprised five sections: interest in and education about bereavement; a Likert scale to measure nurses' views about bereavement care; information about the practice with which the nurse had links; bereavement care provided by the practice; and demographics. RESULTS: A 62% response rate was achieved following two reminders. Sixty-nine per cent reported having an interest in bereavement support. Logistic regression modelling identified older age of the nurse and district of employment as the best predictors of interest in bereavement, and older age of the nurse, district of employment and higher level of academic qualification (having a diploma or degree) as the best predictors of active follow-up bereavement visiting. Ninety five percent of district nurses believed their role should involve visiting bereaved relatives/carers of patients they have nursed, but only 19% believed they should visit bereaved people when the deceased was not their patient. CONCLUSIONS: Older age, higher qualifications and district of employment among district nurses were associated with greater interest in bereavement and more proactive care of bereaved people. The findings of this survey have important implications for the training, continued education and the extended role of the nurse in bereavement support.
Adult↗
Growth differentiation factor 9 and bone morphogenetic protein 15 are essential for ovarian follicular development in sheep.
The aim of this study was to test the hypothesis that both growth differential factor 9 (GDF9) and bone morphogenetic protein (BMP15; also known as GDF9B) are essential for normal ovarian follicular development in mammals with a low ovulation rate phenotype. Sheep (9-10 per group) were immunized with keyhole limpet hemocyanin (KLH; control), a GDF9-specific peptide conjugated to KLH (GDF9 peptide), a BMP15-specific peptide conjugated to KLH (BMP15 peptide), or the mature region of oBMP15 conjugated to KLH (oBMP15 mature protein) for a period of 7 mo and the effects of these treatments on various ovarian parameters such as ovarian follicular development, ovulation rate, and plasma progesterone concentrations evaluated. Also in the present study, we examined, by immunohistochemistry, the cellular localizations of GDF9 and BMP15 proteins in the ovaries of lambs. Both GDF9 and BMP15 proteins were localized specifically within ovarian follicles to the oocyte, thereby establishing for the sheep that the oocyte is the only intraovarian source of these growth factors. Immunization with either GDF9 peptide or BMP15 peptide caused anovulation in 7 of 10 and 9 of 10 ewes, respectively, when assessed at ovarian collection. Most ewes (7 of 10) immunized with oBMP15 mature protein had a least one observable estrus during the experimental period, and ovulation rate at this estrus was higher in these ewes compared with those immunized with KLH alone. In both the KLH-GDF9 peptide- and KLH-BMP15 peptide-treated ewes, histological examination of the ovaries at recovery (i.e., approximately 7 mo after the primary immunization) showed that most animals had few, if any, normal follicles beyond the primary (i.e., type 2) stage of development. In addition, abnormalities such as enlarged oocytes surrounded by a single layer of flattened and/or cuboidal granulosa cells or oocyte-free nodules of granulosa cells were often observed, especially in the anovulatory ewes. Passive immunization of ewes, each given 100 ml of a pool of plasma from the GDF9 peptide- or BMP15 peptide-immunized ewes at 4 days before induction of luteal regression also disrupted ovarian function. The ewes given the plasma against the GDF9 peptide formed 1-2 corpora lutea but 3 of 5 animals did not display normal luteal phase patterns of progesterone concentrations. The effect of plasma against the BMP15 peptide was more dramatic, with 4 of 5 animals failing to ovulate and 3 of 5 ewes lacking surface-visible antral follicles at laparoscopy. By contrast, administration of plasma against KLH did not affect ovulation rate or luteal function in any animal. In conclusion, these findings support the hypothesis that, in mammals with a low ovulation rate phenotype, both oocyte-derived GDF9 and BMP15 proteins are essential for normal follicular development, including both the early and later stages of growth.
Animals↗
Formation of ovarian follicles during fetal development in sheep.
The origin of follicle (i.e., pregranulosa) cells that become the somatic component of primordial follicles is obscure. In addition, information regarding the structural changes that accompany the concomitant regression of ovigerous cords and the appearance of primordial follicles is lacking. In the present study, ovine ovaries collected at frequent time intervals between Day 38 and Day 100 of fetal life were examined by light and electron microscopy. To gain new information regarding the origin of follicular cells, incorporation of 5-bromo-2'-deoxyuridine was used to identify proliferating cells at selected stages of development. Based on the location and identity of proliferating cells, apoptotic cells, and sequential changes in histoarchitecture, we hypothesize 1) that most (i.e., >95%) of the granulosal cells in newly formed primordial follicles originate from the ovarian surface epithelium; 2) that the sequential events leading to follicle formation take place entirely within ovigerous cords, with the first follicles forming at the interface of the cortex and medulla; and 3) that the loss (i.e., >75%) of germ cells, but not of somatic cells, within the ovigerous cords is a means by which each surviving oocyte gains additional pregranulosal cells before follicle formation. Conceptual models detailing the chronology of developmental events involved in the formation of primordial follicles in sheep are discussed.
Animals↗
Osteoprotegerin abrogates chronic alcohol ingestion-induced bone loss in mice.
To investigate the role of osteoprotegerin (OPG) on alcohol (ethanol)-mediated osteoporosis, we measured a variety of bone remodeling parameters in mice that were either on a control diet, an ethanol (5%) diet, or an ethanol (5%) diet plus OPG administration. OPG diminished the ethanol-induced (1) decrease in bone mineral density (BMD) as determined by dual-energy densitometry, (2) decrease in cancellous bone volume and trabecular width and the increase of osteoclast surface as determined by histomorphometry of the femur, (3) increase in urinary deoxypyridinolines (Dpd's) as determined by ELISA, and (4) increase in colony-forming unit-granulocyte macrophage (CFU-GM) formation and osteoclastogenesis as determined by ex vivo bone marrow cell cultures. Additionally, OPG diminished the ethanol-induced decrease of several osteoblastic parameters including osteoblast formation and osteoblast culture calcium retention. These findings were supported by histomorphometric indices in the distal femur. Taken together, these data show that OPG diminishes ethanol-induced bone loss. Furthermore, they suggest that OPG achieves this through its ability to abrogate ethanol-induced promotion of osteoclastogenesis and promote osteoblast proliferation.
Animals↗
A study of female nurses combining partner and parent roles with working a continuous three-shift roster: the impact on sleep, fatigue and stress.
This study of female nurses working a continuous 3-shift roster found that the average sleep duration per 24-hours across the roster is almost one hour less for nurses who combine shiftwork, partner and parent roles. In particular, they are not free to use the later starting afternoon shift as an opportunity to repay the sleep debt incurred on night shift. The results show an interaction between work and family roles resulting in chronic fatigue that is a risk factor especially when combined with the acute fatigue associated with night work. The sleep record data is supported by interview data which highlight shiftwork as a stressor that reduces the opportunity for participation in social and leisure activities by all three of the groups studied: single, partnered and partnered with children. The strain of shiftwork on personal and social relationships reduces the resources available for coping with the emotional and physical stressors encountered by nurses in their work and family roles.
Adult↗
Clinical inquiries. What are the indications for urodynamic testing in older adults with incontinence?
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Evidence-Based Medicine↗
Application of genetically altered models as replacement for the lifetime mouse bioassay in pharmaceutical development.
The international pharmaceutical regulatory academic and industrial toxicology communities are collaborating to improve the efficiency and effectiveness of cancer hazard identification based on dramatic improvements in our understanding of the cancer process. Guidelines emanating from the International Conference on Harmonization provide for use of in vivo alternatives. Standard practices utilizing lifetime rat and mouse studies are recognized as seriously flawed with over 80% false positive rates. Furthermore, tobacco, the most important human carcinogen commercialized by industry, is negative in these traditional lifetime studies. The lifetime mouse bioassay is generally recognized in pharmaceutical development as not adding value in safety assessment. An international consortium under the aegis of ILSI has recently completed an evaluation of alternative mouse cancer models. Transgenic models are less expensive, use fewer animals and take less time than traditional lifetime bioassays. These alternative models have now been sufficiently evaluated to be considered useful in the safety assessment plan for pharmaceuticals in development. Specifically for example, the rasH2 appears useful in detecting nongenotoxic as well as genotoxic rodent tumorigens with improved concordance with human response. The p53+/- heterozygous mouse apparently identifies hormonal carcinogenic mechanisms, immunosuppressive carcinogens, and genotoxic carcinogens. The TG:AC predicts for rodent tumorigens applied topically. Recent experiences at FDA, CPMP, and MHW indicate that with good planning and agency interactions, regulatory acceptability can be anticipated.
Animals↗
Anorexia nervosa and the efficacy of an eating disorder service.
Anorexia nervosa is often a chronic and severe disorder in which morbidity and mortality are high. This article describes the treatments used at The Priory Hospital's eating disorder service. The findings of an audit and follow-up study found that 85 per cent of the anorexic patients were successfully helped to gain weight (up to their normal weight) at a rate of about 1 kg per week. In a follow-up study four years later 80 per cent were doing reasonably well.
Adult↗