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Biomedical subjects

E Davies

Publications and source records attributed to E Davies.

At least 19 recordsLinked to original sources

How is place of death from cancer changing and what affects it? Analysis of cancer registration and service data.

We aimed to compare trends in place of cancer death with the growth of palliative care and nursing home services, and investigate demographic, disease-related and area influences on individual place of death, using registration data for 216404 patients with breast, lung, colorectal and prostate cancer and aggregate data on services in South East England. Between 1985 and 1994 there was a trend away from hospital death (67-44%), to home (17-30%) and hospice death (8-20%). After 1995, this partly reversed. By 2002, hospital death rose to 47%, home death dropped to 23%, hospice death remained stable and nursing home death rose from 3 to 8%. Numbers of palliative care services increased, but trends for hospice and nursing home deaths most clearly followed the beds available. Cancer diagnosis and treatment influenced individual place of death, but between 1998 and 2002, age and area of residence were associated with most variation. Older patients and those living in more deprived areas died more often in hospitals and less often at home. Despite more palliative care services the proportion of people dying at home has not increased. Variation by age, deprivation and area of residence is unlikely to reflect patient preference. More active surveillance and planning must support policies for choice in end of life care.

Age Factors↗

Lack of annexin 1 results in an increase in corticotroph number in male but not female mice.

Annexin 1 (ANXA1) is a member of the annexin family of phospholipid- and calcium-binding proteins with a well demonstrated role in early delayed (30 min to 3 h) inhibitory feedback of glucocorticoids in the pituitary. We have examined corticotrophs in wild-type and ANXA1 knockout mice to determine the effects of lack of ANXA1 in male and female animals. Anterior pituitary tissue from ANXA1 wild-type, heterozygote and null mice was fixed and examined (i) by confocal immunocytochemistry to determine the number of corticotrophs and (ii) by electron microscopy to examine the size, secretory granule population and secretory machinery of corticotrophs. No differences in these parameters were detected in female mice. In male ANXA1 null mice, there were approximately four-fold more corticotrophs than in wild-type animals. However, the corticotrophs in ANXA1 null mice were smaller and had reduced numbers of secretory granules (the reduction in granules paralleled the reduction in cell size). No differences in the numerical density of folliculo-stellate, gonadotroph, lactotroph or somatotroph cells were detected in male ANXA1 null mice. Plasma corticosterone, adrenocorticotrophic hormone (ACTH) and pituitary pro-opiomelanocortin mRNA were unchanged but pituitary ACTH content was increased in male ANXA1 null mice. Interleukin (IL)-6 pituitary content was significantly elevated in male and reduced in female ANXA1 null mice compared to wild-type. In conclusion, these data indicate that ANXA1 deficiency is associated with gender-specific changes in corticotroph number and structure, via direct actions of ANXA1 and/or indirect changes in factors such as IL-6.

Adrenocorticotropic Hormone↗

Prejudice and schizophrenia: a review of the 'mental illness is an illness like any other' approach.

OBJECTIVE: Many anti-stigma programmes use the 'mental illness is an illness like any other' approach. This review evaluates the effectiveness of this approach in relation to schizophrenia. METHOD: The academic literature was searched, via PsycINFO and MEDLINE, to identify peer-reviewed studies addressing whether public espousal of a biogenetic paradigm has increased over time, and whether biogenetic causal beliefs and diagnostic labelling are associated with less negative attitudes. RESULTS: The public, internationally, continues to prefer psychosocial to biogenetic explanations and treatments for schizophrenia. Biogenetic causal theories and diagnostic labelling as 'illness', are both positively related to perceptions of dangerousness and unpredictability, and to fear and desire for social distance. CONCLUSION: An evidence-based approach to reducing discrimination would seek a range of alternatives to the 'mental illness is an illness like any other' approach, based on enhanced understanding, from multi-disciplinary research, of the causes of prejudice.

Attitude to Health↗

Evaluation of the effect of endometriosis on oocyte quality and endometrial environment by comparison of donor and recipient outcomes following embryo transfer in a shared oocyte program.

PURPOSE: To determine whether endometriosis has an effect on the uterine environment vs the oocyte itself. METHODS: A retrospective study comparing pregnancy outcome of infertile donors sharing oocytes with donor egg recipients according to whether the donor or recipient had endometriosis or not was carried out. RESULTS: There were 26 transfers from donors with endometriosis vs 144 in donors without endometriosis. The clinical and viable PRs and implantation rates were 42.9%, 38.1%, and 29.4% for the endometriosis group vs 60.9%, 51.9%, and 33.2%, respectively, for donors without endometriosis (p = NS). The clinical and viable PRs and implantation rates for donors with endometriosis per ET was 41.2%, 35.3%, and 20.4% vs 50.4%, 48.0% and 28.4% for donors without endometriosis, respectively (p = NS). CONCLUSIONS: Though no significant differences were found in donors with or without endometriosis in any parameters, there did appear to be a trend for lower PRs and implantation rates in women undergoing controlled ovarian hyperstimulation.

Adult↗

The aldosterone synthase (CYP11B2) and 11beta-hydroxylase (CYP11B1) genes are not expressed in the rat heart.

Aldosterone synthase (CYP11B2) and 11beta-hydroxylase (CYP11B1) catalyze the production of aldosterone and corticosterone, respectively, in the rat adrenal cortex. Recently, there has been some debate as to whether these corticosteroids are also produced in the hearts of rodents and humans, possibly contributing to the development of hypertrophy and myocardial fibrosis. To investigate this, we have used our established, highly sensitive real-time quantitative RT-PCR method to measure CYP11B1 and CYP11B2 mRNA levels in adrenal and cardiac tissue from several rat models of cardiovascular pathology. We have also studied isolated adult rat ventricular myocytes treated with angiotensin II and ACTH. Total RNA was isolated from the adrenal and cardiac tissue of 1) male Wistar rats with heart failure induced by coronary artery ligation and sham-operated controls; 2) stroke-prone spontaneously hypertensive rats and Wistar Kyoto rats as controls; 3) cyp1a1Ren-2 transgenic rats and Fischer controls; 4) isolated adult Sprague-Dawley ventricular myocytes incubated with 11-deoxycorticosterone (DOC), DOC plus angiotensin II, or DOC plus ACTH. Adrenal CYP11B2 expression was significantly increased in transgenic rats compared with Fischer controls (1.3 x 10(9)+/- 1.2 x 10(9) vs. 2.1 x 10(7) +/- 7.0 x 10(6) copies/microg RNA; P < 0.05). There were no other significant differences in adrenal CYP11B2 or CYP11B1 expression between the model animals and their respective controls. Cardiac CYP11B1 and CYP11B2 mRNA transcript levels from all in vivo and in vitro groups were never greater than 100 copies per microgram total RNA and therefore too low to be detected reproducibly. This suggests that cardiac corticosteroid production is unlikely to be of any physiological or pathological significance.

Adrenal Glands↗

Waiting times for radiotherapy: variation over time and between cancer networks in southeast England.

The aim of this study was to investigate variations in the length of time that patients with cancer wait from diagnosis to treatment with radiotherapy. A total of 57,426 men and 71,018 women diagnosed with cancer between 1992 and 2001 and receiving radiotherapy within 6 months of diagnosis were identified from the Thames Cancer Registry database. In total, 12 sites were identified for which a substantial number or proportion of patients received radiotherapy: head and neck, oesophagus, colon, rectum, lung, nonmelanoma skin cancer, breast, uterus, prostate, bladder, brain and non-Hodgkin's lymphoma. Median waiting times from diagnosis to radiotherapy were calculated, together with the proportion of patients who received radiotherapy within 60 days of diagnosis, and analysed by year of diagnosis, cancer site, deprivation quintile, age at diagnosis, sex and cancer network of either residence or treatment. Logistic regression was used to adjust the proportion receiving treatment within 60 days for the effects of the other factors. There were significant differences in the proportions receiving radiotherapy within 60 days between different networks and different cancer sites, which remained after adjustment. Median waiting times varied from 42 to 65 days across networks of residence, with the adjusted proportion treated within 60 days ranging from 44 to 71%. There was no difference between male and female patients after adjustment for the other factors, particularly site. There was a highly significant trend over time: the median wait increased from 45 days in 1992 to 76 days in 2001, while the adjusted proportion being treated within 60 days declined by almost a half, from 64 to 35%, over the same period.

Adult↗

Views of bereaved relatives about quality of survival after radiotherapy for malignant cerebral glioma.

OBJECTIVE: To explore the views of bereaved relatives about quality of survival after radiotherapy for malignant cerebral glioma. DESIGN: Semistructured interviews with the bereaved relatives of 56 previously studied patients with glioma. SETTING: Patients treated at six London hospitals from 1990 to 1992 surviving between one and 46 months (median, eight). SUBJECTS: Fifty six relatives (44 spouses, 12 others) seen four to six months after bereavement and 20 again at 13 months. MAIN OUTCOME MEASURES: Views about quality of life and satisfaction with radiotherapy. RESULTS: Relatives described quality of life as "good or acceptable" when patients carried on some normal activities or enjoyed social relationships. They described restricted and dependent states, constant deterioration, or loss of social interaction as giving "poor or unacceptable" quality of life. Length of time lived in such states also appeared important. Relatives' views of good or acceptable quality of life were independently related to low initial cognitive or personality change or low distress in the patient after diagnosis, and to their subsequent survival free from physical disability for at least one month. Satisfaction with radiotherapy was related to low initial distress, some degree of surgical resection, and overall length of survival longer than six months. CONCLUSIONS: Carefully exploring the views of bereaved relatives can bring a useful perspective to difficult treatment decisions. Their values support including disability and distress in quality of life measures, but cast doubt on the QALY-type approach of using full years of survival or time free from disability to judge whether treatments are worthwhile.

Adult↗

Hearing the patient's voice? Factors affecting the use of patient survey data in quality improvement.

OBJECTIVE: To develop a framework for understanding factors affecting the use of patient survey data in quality improvement. DESIGN: Qualitative interviews with senior health professionals and managers and a review of the literature. SETTING: A quality improvement collaborative in Minnesota, USA involving teams from eight medical groups, focusing on how to use patient survey data to improve patient centred care. PARTICIPANTS: Eight team leaders (medical, clinical improvement or service quality directors) and six team members (clinical improvement coordinators and managers). RESULTS: Respondents reported three types of barriers before the collaborative: organisational, professional and data related. Organisational barriers included lack of supporting values for patient centred care, competing priorities, and lack of an effective quality improvement infrastructure. Professional barriers included clinicians and staff not being used to focusing on patient interaction as a quality issue, individuals not necessarily having been selected, trained or supported to provide patient centred care, and scepticism, defensiveness or resistance to change following feedback. Data related barriers included lack of expertise with survey data, lack of timely and specific results, uncertainty over the effective interventions or time frames for improvement, and consequent risk of perceived low cost effectiveness of data collection. Factors that appeared to have promoted data use included board led strategies to change culture and create quality improvement forums, leadership from senior physicians and managers, and the persistence of quality improvement staff over several years in demonstrating change in other areas. CONCLUSION: Using patient survey data may require a more concerted effort than for other clinical data. Organisations may need to develop cultures that support patient centred care, quality improvement capacity, and to align professional receptiveness and leadership with technical expertise with the data.

Data Collection↗

Effects of culture with TNF-alpha, TGF-beta and insulin on sulphotransferase (SULT 1A1 and 1A3) activity in human colon and neuronal cell lines.

The aim of the study was to determine whether the expression of sulphotransferase enzymes could be affected by the presence of cytokines or peptide hormones. The effects of cytokines (TNF-alpha and TGF-beta) and insulin on sulphotransferase (SULT 1A1 and 1A3) activity were studied in a human neuronal cell line (SK-N-SH) and a human gastrointestinal tract cell line (HT-29). Cells were cultured with varying concentrations of TNF-alpha, TGF-beta or insulin for 24 h; the SULT 1A1 isoform in the 2 cell lines showed different optimal substrate concentrations. There were no direct effects of cytokines on enzyme activity. Culture with TNF-alpha increased activity of both SULT 1A1 and 1A3 in the HT-29 cells; TGF-beta also increased activities of both isoforms but to a lesser extent; insulin increased activity of SULT 1A1 only. The cytokines and insulin had relatively little effect on sulphotransferase activity in the neuronal cell line. These results suggest that, unlike neuronal cells, gastrointestinal cells may respond to physiological states by altering sulphotransferase activity. As certain substrates such as diet-derived heterocyclic amines are bioactivated by sulphation to produce carcinogenic metabolites this may be a factor in the increased incidence of colorectal cancer in patients with inflammatory bowel disease or diabetes.

Arylsulfotransferase↗

Effect of antagonists vs agonists on in vitro fertilization outcome.

PURPOSE: To compare outcome following in vitro fertilization-embryo transfer (IVF-ET) using controlled ovarian hyperstimulation (COH) regimens using either the gonadotropin-releasing hormone (GnRH) agonist leuprolide acetate vs the GnRH antagonist ganirelix. METHODS: Women needing IVF for conception were randomly assigned to 300 IU of gonadotropins with ganirelix used in the follicular phase when a follicle with a 14 mm average diameter was attained vs a regimen using leuprolide acetate from the mid-luteal phase of the previous cycle. RESULTS: There were no differences found in clinical, ongoing, delivered pregnancy rates or implantation rates between groups. CONCLUSIONS: The use of GnRH antagonists do not seem to reduce IVF outcome compared to using GnRH agonists in COH regimens.

Adult↗

Two year survival after malignant cerebral glioma: patient and relative reports of handicap, psychiatric symptoms and rehabilitation.

PURPOSE: To describe patient outcomes and contact with rehabilitation services two years after the diagnosis of malignant cerebral glioma. METHODS: A cross-sectional interview study of patients treated two years previously between 1990-1992 at six London hospitals. Twenty-two of 181 treated patients were found alive (12%). Fifteen were well enough to approach and 12 male patients (aged 28-60 years) and ten relatives (9 female, 1 male) could be seen by 1994. Semi-structured home interviews carried out separately with patients and relatives assessed return to previous work or activity, patient and relative reports of handicap, psychiatric symptoms, estimated percentage drop in verbal and non-verbal performance and contact with rehabilitation services. RESULTS: Using accounts of return to work or normal activity two years after treatment, five patients were classed as broadly 'active' and seven as 'inactive'. The 'active' group appeared to have few physical or cognitive problems or were able to adapt their work around these. Disagreement between patients and relatives about handicap, patient and relative psychiatric symptoms and severe neuropsychological deficit appeared to cluster in the 'inactive group'. No patient had been formally referred for rehabilitation. CONCLUSIONS: Patient outcome, in terms of managing work and everyday activities, can be very good for some two-year survivors. For others, patient and relative accounts and neuropsychological testing may disclose a range of problems. Such inquiry might suggest referral for rehabilitation or other support.

Activities of Daily Living↗

Survival of Tdc transposable elements of the En/Spm superfamily in the carrot genome.

Three subfamilies of the En/Spm-type transposable element of carrot, Tdc A, B, and C, were characterized. It was supposed that the Tdc A subfamily may include autonomous elements which can produce transposases. Tdc B elements are defective, but still generate transcripts containing mutant open reading frame (ORF) sequences for transposases. The single member of the Tdc C group recovered seems to be a pseudogene. The sequences of the transposase ORFs of Tdc A and Tdc B elements are more highly conserved than those of the 5; and 3; untranslated regions and introns, as is found in other structural genes that are subject to selection. These observations indicate that the mutations in the nucleotide sequences of the Tdc elements occurred in the host genome. However, the mutations in the 5; and 3; untranslated regions and introns, which may not be sufficient to prevent transposition, accumulated in autonomous elements, which could transpose and produce copies. When the reproduction rate and the rate of disabling mutations reached an equilibrium, that is, when the birth rate of the transposable elements in the genome equalled the death rate, the population of elements achieved a stationary state in the genome, and could thus survive.

Amino Acid Sequence↗

Drug errors: what role do nurses and pharmacists have in minimizing the risk?

A multi-professional project was carried out in order to identify the interventions that nurses and pharmacists make in relation to drug administration (an intervention refers to 'the process of querying a prescription with a prescriber'). The project highlights the importance of both these occupational groups in identifying prescribing errors and preventing them from being translated into actual medication errors. It also identifies the need for adequate training for nursing and medical staff, along with system changes, in order to minimize the risk of medication errors.

Drug Prescriptions↗

Efficacy of sharing oocytes from compensated donors between two recipients.

PURPOSE: To see if sharing of donated oocytes from a compensated donor lowers outcome following embryo transfer compared to recipients keeping all oocytes. METHOD: Retrospective review. Recipients have the option of keeping all oocytes or sharing to reduce costs. RESULTS: There were equal clinical, and ongoing/delivered pregnancy rates and implantation rates in the two groups. There were almost twice as many frozen embryos available to recipients who did not share for potential future use. CONCLUSIONS: Sharing of oocytes between two recipients reduces the financial burden for the recipient without affecting efficacy. Such a policy would make more oocytes available to recipients and thus shorten the long waiting times.

Cost Savings↗

An evaluation of the efficacy of using oocyte donors aged 36-39.

PURPOSE: To determine if oocyte donors aged 36-39 can provide adequate pregnancy rates for recipients. METHODS: Retrospective analysis of clinical, ongoing/delivered pregnancy and implantation rates for a group of recipients receiving oocytes from a pilot group of older donors. RESULTS: Comparable pregnancy and implantation rates were found in recipients transferring embryos derived from donors aged 36-39 as recipients using oocytes from donors < or = 35. CONCLUSIONS: The demonstration of adequate outcome following embryo transfer from embryos derived from fertilization of oocytes from donors aged 36-39 should expand the pool of donor oocytes and reduce the long waiting times for recipients.

Adult↗

Association studies between microsatellite markers within the gene encoding human 11beta-hydroxysteroid dehydrogenase type 1 and body mass index, waist to hip ratio, and glucocorticoid metabolism.

Two isozymes of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) interconvert active cortisol (F) and inactive cortisone (E). 11beta-HSD1 is an oxo-reductase (E to F) expressed in several glucocorticoid target tissues, including liver and adipose tissue, where it facilitates glucocorticoid-induced gluconeogenesis and adipocyte differentiation, respectively. We have isolated a full-length HSD11B1 genomic clone; the gene is more than 30 kb in length, not 9 kb in length as previously reported, principally due to a large intron 4. Two polymorphic (CA)(n) repeats have been characterized within intron 4: a CA(19) repeat 2.7 kb 3' of exon 4 and a CA(15) repeat 3 kb 5' of exon 5. The microsatellites, CA(19) and CA(15), were PCR amplified using fluorescent primers and were genotyped on an ABI 377 DNA sequencer from DNA of 413 normal individuals enrolled in the MONICA study of cardiovascular risk factors and 557 Danish men (ADIGEN study), of whom 234 were obese [body mass index (BMI), >/=31 kg/m(2) ] at draft board examination and 323 were randomly selected controls from the draftee population with BMI below 31 kg/m(2) (mean +/- SE, 21.7 +/- 0.41). Genotypic data from the normal MONICA cohort was compared with gender, 5beta-tetrahydrocortisol+5alpha-tetrahydrocortisol/tetrahydrocortisone ratio, and waist to hip (W:H) ratio. When analyzed by allele length (0, 1, or 2 short alleles) for the CA(19) marker, there was a trend toward a higher 5beta-tetrahydrocortisol+5alpha-tetrahydrocortisol/tetrahydrocortisone ratio (P = 0.058) and an increased W:H ratio (2 vs. 0.1 short; P(c) = 0.10) with overrepresentation of short alleles. The opposite was true for the CA(15) locus, with longer alleles at this locus predicting increased 11beta-HSD1 activity, particularly in females. Genotypic data from the ADIGEN case-control population was compared with clinical markers of obesity such as BMI and W:H ratio. There was no significant difference in the distribution of either microsatellite marker between lean and obese groups. Allele distributions were binomial, as seen for the MONICA cohort, and the data were split accordingly (zero, one, or two short alleles). No significant association was seen between grouped alleles and the clinical parameters. No association was observed between HSD11B1 genotype and BMI in either population. These data suggest that 11beta-HSD1 is not a major factor in explaining genetic susceptibility to obesity per se. However, weak associations between HSD11B1 genotype, increased 11beta-HSD1 activity, and W:H ratio suggest that polymorphic variability at the HSD11B1 locus may influence susceptibility to central obesity through enhanced 11beta-HSD1 activity (E to F conversion) in visceral adipose tissue.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗