PubMed Health⌕ Search

Biomedical subjects

M Morley

Publications and source records attributed to M Morley.

At least 19 recordsLinked to original sources

Diagnostic adequacy and accuracy of fine needle aspiration cytology in neck lump assessment: results from a regional cancer network over a one year period.

AIM: To establish the diagnostic accuracy and adequacy of fine needle aspiration cytology (FNAC) within a regional cancer network, and to determine what service improvements may be required to allow successful implementation of an FNAC-based, 'one-stop' head and neck clinic, as proposed by the current National Institute for Clinical Excellence guidelines. MATERIALS AND METHODS: The Sussex cancer network serves a population of 1,200,000 and contains five hospitals within three acute trusts. In 2004, an audit was undertaken retrospectively to examine the diagnostic adequacy and accuracy of head and neck FNAC across the network. Comparisons were then made with the results of subsequent relevant surgery. For the purposes of the audit, FNAC was subdivided into three main groups: salivary gland, thyroid gland and neck node. As part of the data analysis, we also noted the clinical source of the FNAC and whether it was performed blind or under image guidance. RESULTS: In 2004, 712 FNAC procedures were undertaken in 647 patients, 276 of whom underwent subsequent surgery. Fine needle aspiration cytology was non-diagnostic in 52 per cent of patients in the neck node group, in 50 per cent in the salivary gland group and in 30 per cent in the thyroid group. With these non-diagnostic results removed, statistical analysis was performed on data from those patients who had undergone both FNAC and subsequent surgery. This gave a sensitivity of 89 per cent and a specificity of 57 per cent in the neck node group, a sensitivity of 64 per cent and specificity of 100 per cent in the salivary gland group, and a sensitivity of 62 per cent and specificity of 86 per cent in the thyroid group. Diagnostic problems with FNAC were noted, particularly in the differentiation of reactive nodal hyperplasia from lymphoma and in diagnosing follicular thyroid lesions. Ultrasound guidance was used in 50 per cent of the thyroid FNAC procedures but in only a minority of patients in the neck node and salivary gland groups. CONCLUSION: This audit demonstrated widespread diagnostic difficulties associated with head and neck FNAC in a large patient sample. It is likely that these problems will be mirrored in other cancer networks. In order for one-stop head and neck clinics to succeed, the non-diagnostic rate of FNAC in particular must be minimised. There are strategies to enable this, depending on local resources, including increased access to cytologists or cytology technicians, diagnostic ultrasound, image guidance for FNAC and the use of ultrasound-guided core biopsy.

Biopsy, Fine-Needle↗

A decision support framework for sustainable urban water planning and management in new urban areas.

The paper discusses issues of decision support within the context of sustainable development and more specifically sustainable water cycle management to provide a context and a rationale for the decision support approach adopted within an on-going U.K. EPSRC-funded project, WaND. The paper proposes a set-up for a flexible, upgradeable, efficient and modular decision support framework and associated tools. Furthermore, the paper presents early prototypes of three decision support tools developed within the proposed framework including initial results for one of them.

Cities↗

Motor neuron pathology in experimental autoimmune encephalomyelitis: studies in THY1-YFP transgenic mice.

Using adult male C57BL/6 mice that express a yellow fluorescent protein transgene in their motor neurons, we induced experimental autoimmune encephalomyelitis (EAE) by immunization with myelin oligodendrocyte glycoprotein peptide 35-55 (MOG peptide) in complete Freund's adjuvant (CFA). Control mice of the same transgenic strain received CFA without MOG peptide. Early in the course of their illness, the EAE mice showed lumbosacral spinal cord inflammation, demyelination and axonal fragmentation. By 14 weeks post-MOG peptide, these abnormalities were much less prominent, but the mice remained weak and, as in patients with progressive multiple sclerosis, spinal cord atrophy had developed. There was no significant loss of lumbar spinal cord motor neurons in the MOG peptide-EAE mice. However, early in the course of the illness, motor neuron dendrites were disrupted and motor neuron expression of hypophosphorylated neurofilament-H (hypoP-NF-H) immunoreactivity was diminished. By 14 weeks post-MOG peptide, hypoP-NF-H expression had returned to normal, but motor neuron dendritic abnormalities persisted and motor neuron perikaryal atrophy had appeared. We hypothesize that these motor neuron abnormalities contribute to weakness in this form of EAE and speculate that similar motor neuron abnormalities are present in patients with progressive multiple sclerosis.

Animals↗

Evaluation of a hypertension screening programme in Independence, Belize.

This study assesses the effectiveness of a hypertension-screening programme in Independence, Belize. Forty-nine of the 101 patients screened were found to have elevated blood pressure readings and were advised to seek medical care. Four months later, interviews with 35 of the 49 patients from the hypertensive group revealed that 85.7% of the patients had sought medical care. Women, elderly patients and patients with a previous history of hypertension were more likely than men, younger patients and those without a history of hypertension to seek follow-up medical care. The screening programme successfully directed a high proportion of patients with elevated blood pressure to seek appropriate medical care.

Adolescent↗

Requesting organ donation: the case of self-efficacy--effects of the European Donor Hospital Education Programme (EDHEP).

One of the major reasons for the shortage of donor organs is the high number of refusals by relatives. Studies have shown that the quality of communication with bereaved relatives influences whether to object or agree to organ and/or tissue donation. Breaking news of brain stem death, approaching relatives for permission to donate organs while also appropriately managing emotional reactions of relatives are complex tasks, which require knowledge of the domains as well as adequate skills to communicate information and understanding. In this study the effect of the European Donor Hospital Education Programme (EDHEP) on the self-efficacy of Intensive Care staff is evaluated. Self-efficacy scores significantly improved after attending EDHEP; an effect that was maintained at six month follow-up. EDHEP participants with high baseline scores on self-efficacy, maintained the increase at follow-up. EDHEP participants with low baseline scores on self-efficacy showed the greatest increase at the post-test. Increases in self-efficacy were significantly related to decreases in the perceived difficulty of requesting. Experience had a significant effect on both self-efficacy beliefs and perceived difficulty of requesting donation. As self-efficacy beliefs are perceived as better predictors for future behaviour than prior attainments, the results call for further research in this domain. The data indicate that training programmes should be tailored not only to working circumstances of participants, but should also take levels of experience and self-efficacy into account. Further study is necessary and the best way to proceed is to relate the outcomes of this study to behavioural outcomes.

Attitude of Health Personnel↗

Modulation of gene expression by androgen and oestrogens in the testis and prostate of the adult rat following androgen withdrawal.

Androgens are important for the structural and functional integrity of the testis and the prostate and this may in part be mediated by the aromatisation of testosterone to oestradiol. The aim of the present study was to establish an in vivo model that would allow the identification of genes, the expression of which was regulated acutely by androgen and/or oestrogen in the male reproductive system. In rats in which the Leydig cells were ablated by administration of ethane dimethane sulfonate (EDS) 6 days earlier, testosterone esters (T) were administered from day 0 (To), and additional animals were administered either T, 17beta-oestradiol benzoate (EB) or diethylstilbestrol (DES) for 1 or 4 h on day 6 after EDS-treatment. Nuclear immunoexpression of the androgen receptor (AR) was reduced or absent from the testis but unaffected in the ventral prostate following these treatments. ERbeta immunoexpression in these tissues was unchanged. Northern blot analysis showed that EB and DES as well as T administration 4 h earlier could modulate mRNA expression of two androgen-responsive genes, C3 and SGP-2, in the prostate. The co-administration of T or EB with the AR antagonist, flutamide, or with the ER antagonist, ICI 182,780 (ICI), did not block the suppression of SGP-2 mRNA expression by T or EB. In contrast, the upregulation of C3 mRNA expression by T was successfully antagonised by both flutamide and by ICI. A preliminary evaluation of the expression of three Sertoli cell and five germ cell mRNAs revealed that their expression was not steroid regulated. Our results support the hypothesis that the action of testosterone in the male reproductive system may in part be mediated by its conversion to oestradiol. This in vivo model should prove of value in future studies to identify androgen and oestrogen regulated genes in the male reproductive system.

Androgen-Binding Protein↗

Integration of cytogenetic landmarks into the draft sequence of the human genome.

We have placed 7,600 cytogenetically defined landmarks on the draft sequence of the human genome to help with the characterization of genes altered by gross chromosomal aberrations that cause human disease. The landmarks are large-insert clones mapped to chromosome bands by fluorescence in situ hybridization. Each clone contains a sequence tag that is positioned on the genomic sequence. This genome-wide set of sequence-anchored clones allows structural and functional analyses of the genome. This resource represents the first comprehensive integration of cytogenetic, radiation hybrid, linkage and sequence maps of the human genome; provides an independent validation of the sequence map and framework for contig order and orientation; surveys the genome for large-scale duplications, which are likely to require special attention during sequence assembly; and allows a stringent assessment of sequence differences between the dark and light bands of chromosomes. It also provides insight into large-scale chromatin structure and the evolution of chromosomes and gene families and will accelerate our understanding of the molecular bases of human disease and cancer.

Chromosome Aberrations↗

GenMapDB: a database of mapped human BAC clones.

GenMapDB (http://genomics.med.upenn.edu/genmapdb) is a repository of human bacterial artificial chromosome (BAC) clones mapped by our laboratory to sequence-tagged site markers. Currently, GenMapDB contains over 3000 mapped clones that span 19 chromosomes, chromosomes 2, 4, 5, 9-22, X and Y. This database provides positional information about human BAC clones from the RPCI-11 human male BAC library. It also contains restriction fragment analysis data and end sequences of the clones. GenMapDB is freely available to the public. The main purpose of GenMapDB is to organize the mapping data and to allow the research community to search for mapped BAC clones that can be used in gene mapping studies and chromosomal mutation analysis projects.

Chromosome Mapping↗

Gonadotropin-releasing hormone receptor in the teleost Haplochromis burtoni: structure, location, and function.

GnRH acts via GnRH receptors (GnRH-R) in the pituitary to cause the release of gonadotropins that regulate vertebrate reproduction. In the teleost fish, Haplochromis burtoni, reproduction is socially regulated through the hypothalamus-pituitary-gonadal axis, making the pituitary GnRH-R a likely site of action for this control. As a first step toward understanding the role of GnRH-R in the social control of reproduction, we cloned and sequenced candidate GnRH-R complementary DNAs from H. burtoni tissue. We isolated a complementary DNA that predicts a peptide encoding a G protein-coupled receptor that shows highest overall identity to other fish type I GnRH-R (goldfish IA and IB and African catfish). Functional testing of the expressed protein in vitro confirmed high affinity binding of multiple forms of GNRH: Localization of GnRH-R messenger RNA using RT-PCR revealed that it is widely distributed in the brain and retina as well as elsewhere in the body. Taken together, these data suggest that this H. burtoni GnRH receptor probably interacts in vivo with all three forms of GNRH:

Amino Acid Sequence↗

Validating screening instruments for cognitive impairment in older South Asians in the United Kingdom.

BACKGROUND: The numbers of older South Asians in the United Kingdom are rising. Investigation of their mental health has been neglected compared to their physical health. OBJECTIVES: This study aimed to determine the sensitivity and specificity of modified versions of two screening instruments for cognitive impairment (Mini-Mental State Examination and Abbreviated Mental Test) in a community-based population. DESIGN: Two-stage study comparing screening instruments against diagnostic interview. SETTING: South, central and north Manchester. SUBJECTS: Community-resident South Asians aged 60 years and over. METHODS: Subjects were approached via their general practitioners and interviewed at home. Sensitivity and specificity for the screening instruments were calculated using receiver operating characteristic (ROC) curve analysis. RESULTS: For the Gujarati population, the MMSE cutoff was >/=24 (sensitivity 100%, specificity 95%) and AMT>/=6 (sensitivity 100%, specificity 95%). For the Pakistani population, the MMSE cutoff was >/=27 (sensitivity 100%, specificity 77%) and AMT>/=7 (sensitivity 100%, specificity 87%). CONCLUSIONS: Culturally modified versions of the Mini-Mental State Examination and Abbreviated Mental Test are acceptable and may have a high degree of sensitivity. They may assist with the recognition of cognitive impairment, if an appropriate cutoff is used.

Aged↗

Screening for cognitive impairment in older African-Caribbeans.

BACKGROUND: There are increasing numbers of older African-Caribbeans in the United Kingdom. Screening instruments are commonly used in the detection of cognitive impairment, but have not been assessed within this population. This study aimed to develop culturally modified versions of screening instruments for cognitive impairment (Mini-Mental State Examination (MMSE) and Abbreviated Mental Test (AMT)) and to determine their sensitivity and specificity in the diagnosis of dementia. METHODS: The instruments were modified using a process involving a community group of African-Caribbeans and an academic group of health professionals. They were used in a two-stage study involving community resident African-Caribbeans aged 60 years or over in inner-city Manchester, comparing the screening instruments against a computerized diagnostic interview. RESULTS: One hundred and thirty people completed the study. The results for the largest subgroup, the Jamaicans (N = 96) were analysed. Effects of gender, age and education on the MMSE and AMT scores were evaluated. The correlations between the screening instruments and diagnostic interview were highly significant (P < 0.001). At appropriate cut-offs both screening instruments demonstrated high sensitivity and acceptable specificity levels. CONCLUSIONS: A defined process with lay input has assisted in producing culturally modified versions of the MMSE and AMT that perform well compared with a diagnostic interview, if an appropriate cut-off is used. They are easy to administer and acceptable to older African-Caribbean people. The results need to be viewed within the limitations of the current study.

Black or African American↗

The European Donor Hospital Education Programme (EDHEP): enhancing communication skills with bereaved relatives.

Intensive care medical and nursing staff self-rate their communication skills as improved following attendance at the European Donor Hospital Education Programme (EDHEP) workshop. A prospective study was conducted to determine what impact EDHEP has on communication skills. Doctor-nurse pairs from 10 experimental and 10 control Intensive Care Units undertook two standardized simulated relative encounters (Breaking Bad News and Donation Request) at three measurement points (pre, post and follow-up). Nurses showed no change in communication skills. Experimental group doctors showed significant improvement in breaking bad news and requesting donation; most of these improvements were not maintained. Control group doctors showed some improvement in breaking bad news, indicating that participating in measurement by itself initiates some transient change in communication skills. Attendance at EDHEP does lead to significant improvement in some, but not all, communication skills essential in breaking bad news and requesting donation. Further research is necessary to determine what factors additional to EDHEP will contribute to enduring change in these particular skills.

Adult↗

Comparative effects of neonatal exposure of male rats to potent and weak (environmental) estrogens on spermatogenesis at puberty and the relationship to adult testis size and fertility: evidence for stimulatory effects of low estrogen levels.

This study investigated whether neonatal exposure of male rats to estrogenic compounds altered pubertal spermatogenesis (days 18 and 25) and whether the changes observed resulted in long-term changes in testis size, mating, or fertility (days 90-100). Rats were treated neonatally with a range of doses (0.01-10 microg) of diethylstilbestrol (DES; administered on alternate days from days 2-12), a high dose of octylphenol (OP; 2 mg administered daily from days 2-12) or bisphenol A (Bis-A; 0.5 mg administered daily from days 2-12), or vehicle, while maintained on a standard soy-containing diet. The effect on the same parameters of rearing control animals on a soy-free diet was also assessed as was the effect of administering such animals genistein (4 mg/kg/day daily from days 2-18). Testis weight, seminiferous tubule lumen formation, the germ cell apoptotic index (apoptotic/viable germ cell nuclear volume), and spermatocyte nuclear volume per unit Sertoli cell nuclear volume were used to characterize pubertal spermatogenesis. Compared with (soy-fed) controls, DES administration caused dose-dependent retardation of pubertal spermatogenesis on day 18, as evidenced by decreases in testis weight, lumen formation, and spermatocyte nuclear volume per unit Sertoli cell and elevation of the germ cell apoptotic index. However, the two lowest doses of DES (0.1 and 0.01 microg) significantly increased spermatocyte nuclear volume per unit Sertoli cell. Similarly, treatment with either OP or Bis-A significantly advanced this and some of the other aspects of pubertal spermatogenesis. Maintenance of control animals on a soy-free diet also significantly advanced lumen formation and spermatocyte nuclear volume per unit Sertoli cell compared with controls fed a soy-containing diet. Administration of genistein reversed the stimulatory effects of a soy-free diet and significantly retarded most measures of pubertal spermatogenesis. In general, plasma FSH levels in the treatment groups changed in parallel to the spermatogenic changes (reduced when pubertal spermatogenesis retarded, increased when pubertal spermatogenesis advanced). By day 25, although the changes in FSH levels largely persisted, all of the stimulatory effects on spermatogenesis seen on day 18 in the various treatment groups were no longer evident. In adulthood, testis weight was decreased dose dependently in rats treated neonatally with DES, but only the lowest dose group (0.01 microg) showed evidence of mating (3 of 6) and normal fertility (3 litters). Animals treated neonatally with OP or Bis-A had normal or increased (Bis-A) testis weights and exhibited reasonably normal mating/fertility. Animals fed a soy-free diet had significantly larger testes than controls fed a soy-containing diet, and this difference was confirmed in a much larger study of more than 24 litters, which also showed a significant decrease in plasma FSH levels and a significant increase in body weight in the males kept on a soy-free diet. Neonatal treatment with genistein did not alter adult testis weight, and although most males exhibited normal mating and fertility, a minority did not mate or were infertile. It is concluded that 1) neonatal exposure of rats to low levels of estrogens can advance the first wave of spermatogenesis at puberty, although it is unclear whether this is due to direct effects of the estrogen or to associated elevation of FSH levels; 2) the effect of high doses of OP and Bis-A on these processes is essentially benign; and 3) the presence or absence of soy or genistein in the diet has significant short-term (pubertal spermatogenesis) and long-term (body weight, testis size, FSH levels, and possibly mating) effects on males.

Aging↗

Effect of chronic administration of an aromatase inhibitor to adult male rats on pituitary and testicular function and fertility.

The aim of the present study was to evaluate the effects of the administration of a potent non-steroidal aromatase inhibitor, anastrozole, on male reproductive function in adult rats. As anastrozole was to be administered via the drinking water, a preliminary study was undertaken in female rats and showed that this route of administration was effective in causing a major decrease in uterine weight (P<0.02). In an initial study in male adult rats, anastrozole (100 mg/l or 400 mg/l) was administered via the drinking water for a period of 9 weeks. Treatment with either dose resulted in a significant increase ( approximately 10%) in testis weight and increase in plasma FSH concentrations (P<0.01) throughout the 9 weeks. Mating was altered in both groups of anastrozole-treated rats, as they failed to produce copulatory plugs. Histological evaluation of the testes from anastrozole-treated rats revealed that spermatogenesis was grossly normal. In a more detailed study, adult rats were treated with 200 mg/l anastrozole via the drinking water for periods ranging from 2 weeks to 1 year. Plasma FSH and testosterone concentrations were increased significantly (P<0.001) during the first 19 weeks of treatment. However, LH concentrations were increased only at 19 weeks (P<0.001) in anastrozole-treated rats, and this coincided with a further increase in circulating and intratesticular testosterone concentrations (P<0.05). No consistent change in inhibin-B concentrations was observed during the study. Suppression of plasma oestradiol concentrations could not be demonstrated in anastrozole-treated animals, but oestradiol concentrations in testicular interstitial fluid were reduced by 18% (P<0.01). Mating was again inhibited by anastrozole treatment, but could be restored by s.c. injection of oestrogen, enabling demonstration that rats treated for 10 weeks or 9 months were still fertile. Testis weight was increased by 19% and 6% after treatment for 19 weeks and 1 year, respectively. Body weight was significantly decreased (P<0.01) by 19 weeks of anastrozole treatment; after 1 year the animals appeared to have less fat as indicated by a 27% decrease in the weight of the gonadal fat pad. The majority of anastrozole-treated animals had testes with normal spermatogenesis but, occasionally, seminiferous tubules showed abnormal loss of germ cells or contained only Sertoli cells. Ten percent of anastrozole-treated animals had testes that appeared to contain only Sertoli cells, and one rat had 'giant' testes in which the tubule lumens were severely dilated. Morphometric analysis of the normal testes at 19 weeks showed no difference in the number of Sertoli cells or germ cells, or the percentage volumes of the seminiferous epithelium, tubule lumens and interstitium between control and anastrozole-treated rats. On the basis of the present findings, oestrogen appears to be involved in the regulation of FSH secretion and testosterone production, and is also essential for normal mating behaviour in male rats. Furthermore, these data suggest that the brain and the hypothalamo-pituitary axis are considerably more susceptible than is the testis to the effects of an aromatase inhibitor. Anastrozole treatment has resulted in a model of brain oestrogen insufficiency.

Anastrozole↗

The European Donor Hospital Education Programme (EDHEP): addressing the training needs of doctors and nurses who break bad news, care for the bereaved, and request donation.

The competence of critical care staff when it comes to death and organ donation can make the difference between a family's agreeing to or refusing the latter. Doctors and nurses often feel uncomfortable approaching relatives about donation and attribute this to a lack of training. Bereaved relatives express dissatisfaction with inappropriate communication and support when brain death is announced and thereafter when a request for donation is made. The European Donor Hospital Education Programme (EDHEP) was designed to meet the training needs of critical care staff in breaking bad news, caring for the bereaved, and requesting donation. EDHEP is a two-part educational package consisting of a presentation about the donor shortage followed by a one-day workshop. The implementation of EDHEP throughout the world has been facilitated through effective national working groups and standardised "train the trainer" courses. Several countries anecdotally report increases in donation following implementation. Controlled evaluation of the effect(s) of EDHEP, which started at the end of 1995, focuses on the satisfaction of the participants with EDHEP, on the competence of the participants in breaking bad news and requesting donation, on the teamwork regarding death and donation, on the satisfaction of bereaved relatives, and on organ donation rates.

Attitude of Health Personnel↗

Making and reading microarrays.

There are a variety of options for making microarrays and obtaining microarray data. Here, we describe the building and use of two microarray facilities in academic settings. In addition to specifying technical detail, we comment on the advantages and disadvantages of components and approaches, and provide a protocol for hybridization. The fact that we are now making and using microarrays to answer biological questions demonstrates that the technology can be implemented in a university environment.

DNA↗

Screening for depression in African-Caribbean elders.

BACKGROUND: There are increasing numbers of older African-Caribbeans in the UK. Primary care staff often feel less confident about diagnosing depression in this group. Screening instruments may assist in making diagnoses in cross-cultural consultations. OBJECTIVE: We aimed to determine the sensitivity and specificity of screening instruments for depression in older African-Caribbean people in Manchester, UK. METHODS: We carried out a two-stage study to compare three screening instruments for depression (Geriatric Depression Scale, Brief Assessment Schedule Depression Cards, Caribbean Culture Specific Screen), with a computerized diagnostic interview for mental health disorders in older adults (Geriatric Mental State). The study was set in inner-city Manchester. The subjects were community-resident African-Caribbeans aged 60 years and over; 227 subjects were approached. Of the 160 people screened, 130 agreed to diagnostic interview. The main outcome measures were Spearman correlation coefficients; these were calculated between each screening instrument and the diagnostic interview. Receiver-operating characteristic (ROC) curve analysis was used to determine appropriate sensitivity and specificity for each instrument. RESULTS: The results for the largest subgroup, the Jamaicans (n = 96/130), demonstrated highly significant correlations between screening instruments and diagnostic interview (P < 0.001). Each instrument had a high sensitivity: Brief Assessment Schedule depression cards (cut-off > or =6; sensitivity 90.9% (95% CI 58.8-99.8), specificity 82.1% (95% CI 74.0-90.3)), Caribbean Culture Specific Screen (cut-off > or =6; sensitivity 90.9% (95% CI 58.8-99.8), specificity 74.1% (95% CI 64.8-83.4)), and Geriatric Depression Scale (cut-off > or =4; sensitivity 100% (95% CI 97.1-100), specificity 69.1% (95% CI 59.6-79.2)). CONCLUSIONS: These screening instruments demonstrate high sensitivity levels, if an appropriate cut-off point is used. The culture-specific instrument did not perform better than the traditional instruments. Health professionals should approach the consultation in a culturally sensitive manner and use the validated instrument they are most familiar with.

Age Distribution↗