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Biomedical subjects

A Morgan

Publications and source records attributed to A Morgan.

At least 37 records · Page 2Linked to original sources

Costs and effectiveness of community postnatal support workers: randomised controlled trial.

OBJECTIVES: To establish the relative cost effectiveness of postnatal support in the community in addition to the usual care provided by community midwives. DESIGN: Randomised controlled trial with six month follow up. SETTING: Recruitment in a university teaching hospital and care provided in women's homes. PARTICIPANTS: 623 postnatal women allocated at random to intervention (311) or control (312) group. INTERVENTION: Up to 10 home visits in the first postnatal month of up to three hours duration by a community postnatal support worker. MAIN OUTCOME MEASURE: General health status as measured by the SF-36 and risk of postnatal depression. Breast feeding rates, satisfaction with care, use of services, and personal costs. RESULTS: At six weeks there was no significant improvement in health status among the women in the intervention group. At six weeks the mean total NHS costs were pound 635 for the intervention group and pound 456 for the control group (P=0.001). At six months figures were pound 815 and pound 639 (P=0.001). There were no differences between the groups in use of social services or personal costs. The women in the intervention group were very satisfied with the support worker visits. CONCLUSIONS: There was no health benefit of additional home visits by community postnatal support workers compared with traditional community midwifery visiting as measured by the SF-36. There were no savings to the NHS over six months after the introduction of the community postnatal support worker service.

Adolescent↗

Binding of the Epstein-Barr virus major envelope glycoprotein gp350 results in the upregulation of the TNF-alpha gene expression in monocytic cells via NF-kappaB involving PKC, PI3-K and tyrosine kinases.

Epstein-Barr virus (EBV) is a human herpesvirus that interacts with various immunocompetent cells that carry the EBV receptor (CD21/CR2). EBV binds to CR2 through its major envelope glycoprotein 350 (gp350). Previously we had demonstrated that EBV and other human herpesviruses are capable of modulating cytokine synthesis through the deregulated expression of cytokine genes interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and interleukin-2 (IL-2). Here we show that, in contrast to infectious EBV, purified recombinant gp350 upregulates TNF-alpha gene expression in human monocyte/macrophages (M/M) as well as in a monocytoid cell line, U937. Our results also demonstrate that this increased expression is due to both enhanced transcription and stability of TNF-alpha mRNA in gp350-treated cells. The specificity of this effect is evidenced by the fact that pre-incubation of cells with anti-CR2 monoclonal antibody OKB7, which blocks binding of gp350 to CR2, inhibits the above mentioned effects of gp350. Furthermore, we demonstrate that activation of TNF-alpha by gp350 is mediated by NF-kappaB through signal transduction pathways involving PKC, PI3-K and tyrosine kinases. To our knowledge this is the first report describing the modulation of TNF-alpha gene expression by the EBV-gp350 molecule following its interaction with the viral receptor CR2 on cells of the monocytic lineage.

Antibodies, Monoclonal↗

Significance of atypical glandular cells of undetermined significance on ThinPrep Papanicolaou smears.

OBJECTIVE: The aim of this study was to assess the incidence and risk factors predictive of significant histopathologic findings among women with atypical glandular cells of undetermined significance (AGCUS) on ThinPrep Papanicolaou smears. METHODS: ThinPrep smears with AGCUS obtained between 1997 and 1999 were reviewed. Patients' charts were reviewed and patients' characteristics, follow-up information, and colposcopy and biopsy results were recorded. Pathologic slides were reviewed. The demographic features of women with favor reactive smears were compared with those with favor neoplasia and risk factors predictive of significant histopathologic findings (high-grade squamous intraepithelial lesion, endometrial hyperplasia, and cervical or endometrial cancers) were calculated. RESULTS: The rate of diagnosis of AGCUS was 0.65%. Eighty-four patients with follow-up information were identified. The demographic features of women with smears favor neoplasia (n = 43) were similar to those with smears favor reactive (n = 41). The rates of incidence of any dysplasia or cancer and significant histopathologic findings were 32.1 and 22.6%, respectively, and were higher among women with smears favor neoplasia than among women with smears favor reactive (41.9% versus 22.0%, P = 0.051, and 34.9% versus 9.8%, P = 0.006, respectively). The subtype of cytology was the only factor that predicted significant histopathologic findings (odds ratio = 5.0, 95% confidence interval 1.6, 15.6, P < 0.010). CONCLUSIONS: In women with AGCUS on ThinPrep smears, significant histopathologic findings were found in 34.9% versus 9.8%, depending on the subtype of the smear (favor neoplasia vs reactive). Further studies are needed to validate the cytologic criteria for subtyping AGCUS smears and base management of women with AGCUS cytology on the subtype of the smear.

Adult↗

Significance of atypical squamous cells of undetermined significance on ThinPrep papanicolaou smears.

OBJECTIVE: The aim of this study was to assess the prevalence and risk factors predictive of dysplasia among women seen in a gynecologic oncology service with the cytologic diagnosis of atypical squamous cells of undetermined significance (ASCUS) on Papanicolaou smears obtained by the ThinPrep method. METHODS: Patients with ASCUS ThinPrep Papanicolaou smears seen at the Division of Gynecologic Oncology, University of Vermont, between 1997 and 1999 were identified. The cytologic smears were reviewed and subtyped into reactive or suggestive of squamous intraepithelial lesion (SIL). The charts of these patients were reviewed and the following information was abstracted: age, gravidity, parity, menopausal status, use of hormonal replacement therapy, smoking, history of pelvic cancer, history of radiation therapy, history of abnormal Papanicolaou smear and its treatment, history of human papillomavirus (HPV) infection, and follow-up information including results of repeat Papanicolaou smears, colposcopy, and biopsies. The prevalence of dysplasia was calculated. The demographic features of women with ASCUS, reactive, were compared with those with ASCUS, SIL, using a two-sample t test, chi(2), and Fisher's exact test. Risk factors predictive of dysplasia were calculated using the odds ratio and the 95% confidence interval. P < 0.05 was considered significant. RESULTS: One hundred twenty-six patients with ASCUS on ThinPrep Papanicolaou smear were identified; 63 patients had ASCUS, reactive, and 63 patients had ASCUS, SIL. The demographic features of both groups were similar. The overall prevalence of dysplasia was 15.9% and was significantly higher among women with ASCUS, SIL, than among women with ASCUS, reactive (25.4% versus 6.4%, P = 0.003). The type of ASCUS cytology (reactive versus SIL), smoking, and history of HPV were significant risk factors for dysplasia (P = 0.003, 0.037, and 0. 042, respectively). CONCLUSIONS: The prevalence of dysplasia among women seen in a gynecologic oncology service with ASCUS cytology on ThinPrep Papanicolaou smears is 15.9%. Women with ASCUS favor SIL, those who smoke, and those with a history of HPV are at higher risk for dysplasia and should be offered colposcopy.

Adult↗

Non-malignant tracheo-gastric fistula following esophagectomy for cancer.

Two cases of neoesophago-tracheal fistula are described. After esophagectomy for cancer a fistula developed between the trachea and the pulled-up stomach probably because of the ischaemic effect of the tracheostomy tube. At single stage repairs, the fistulae were divided and the gastric defects were closed directly. In one case, tracheal resection and anastomosis was necessary. The defect on the membranous trachea in both cases was patched with an autologous fascia lata graft. A left pectoralis major muscle flap was interposed between the suture lines to prevent recurrence of the fistula. Treatment of this potentially life-threatening and rare condition yielded excellent results.

Esophageal Neoplasms↗

The role of the fixation location in inhibition of return.

Experiments that have examined inhibition of return (IOR) have typically used trial sequences in which attention is reoriented to a central fixation location between the presentation of the peripheral cue(s) and the target. In examining the role of the fixation location in IOR, three experiments were conducted in which an exogenous cue was used to reorient attention following a peripheral cue and before the appearance of a target. However, this cue occurred at either the traditional central fixation location or a nonfixated location. The results indicate that reorienting attention to a fixated location results in a significant reduction in the inhibitory effect. The results from the study suggest that IOR could serve as a mechanism that improves the efficiency of visual searches.

Attention↗

The transcriptome of Arabidopsis thaliana during systemic acquired resistance.

Infected plants undergo transcriptional reprogramming during initiation of both local defence and systemic acquired resistance (SAR). We monitored gene-expression changes in Arabidopsis thaliana under 14 different SAR-inducing or SAR-repressing conditions using a DNA microarray representing approximately 25-30% of all A. thaliana genes. We derived groups of genes with common regulation patterns, or regulons. The regulon containing PR-1, a reliable marker gene for SAR in A. thaliana, contains known PR genes and novel genes likely to function during SAR and disease resistance. We identified a common promoter element in genes of this regulon that binds members of a plant-specific transcription factor family. Our results extend expression profiling to definition of regulatory networks and gene discovery in plants.

Arabidopsis↗

Disconnecting hippocampal projections to the anterior thalamus produces deficits on tests of spatial memory in rats.

A disconnection procedure was used to test whether projections from the hippocampus to the anterior thalamic nuclei (AT), via the fimbria-fornix (FX), form functional components of a spatial memory system. The behavioural effects of combined unilateral lesions in the AT and FX were compared when they were either in contralateral hemispheres (AT-FX Contra) or the same hemisphere (AT-FX Ipsi). Other groups received bilateral FX lesions and Sham surgeries. Expt 1 demonstrated that none of these lesions affected performance of an object recognition task, while performance of an object location task, which tests the subjects' preference for an object that has changed location, was impaired in the AT-FX Contra and FX groups. In a T-maze alternation task, however, the FX group was severely impaired while both the AT-FX Ipsi and AT-FX Contra lesion groups showed only a mild impairment. In order to test whether spared crossed projections might support spatial performance in the AT-FX Contra group we then examined the effects of a combined AT-FX Contra lesion coupled with transection of the hippocampal commissure. This combination of lesions produced a severe disruption in spatial memory performance in the water maze, radial arm maze and T-maze, which was significantly greater than that produced by ipsilateral and contralateral AT-FX lesions alone. These results support the notion that disconnection of the AT from their hippocampal inputs produces impairments on a range of spatial memory tasks, but indicate that there are an array of different routes that can subserve this function.

Animals↗

Individual and group psychotherapy with infertile couples.

After reviewing some of the relevant literature, the writers proceed to describe a new development in psychotherapy for couples presenting with relatively unexplained infertility. Several couples who had failed to achieve conception (despite the use of assisted reproductive techniques and personal psychotherapy) were brought together into a supportive-expressive group led by the writers, an experienced analytic cotherapy couple. An interesting outcome is described, and mention made of current plans for a future research project.

Adult↗

A screen for dominant negative mutants of SEC18 reveals a role for the AAA protein consensus sequence in ATP hydrolysis.

An evolutionarily ancient mechanism is used for intracellular membrane fusion events ranging from endoplasmic reticulum-Golgi traffic in yeast to synaptic vesicle exocytosis in the human brain. At the heart of this mechanism is the core complex of N-ethylmaleimide-sensitive fusion protein (NSF), soluble NSF attachment proteins (SNAPs), and SNAP receptors (SNAREs). Although these proteins are accepted as key players in vesicular traffic, their molecular mechanisms of action remain unclear. To illuminate important structure-function relationships in NSF, a screen for dominant negative mutants of yeast NSF (Sec18p) was undertaken. This involved random mutagenesis of a GAL1-regulated SEC18 yeast expression plasmid. Several dominant negative alleles were identified on the basis of galactose-inducible growth arrest, of which one, sec18-109, was characterized in detail. The sec18-109 phenotype (abnormal membrane trafficking through the biosynthetic pathway, accumulation of a membranous tubular network, growth suppression, increased cell density) is due to a single A-G substitution in SEC18 resulting in a missense mutation in Sec18p (Thr(394)-->Pro). Thr(394) is conserved in most AAA proteins and indeed forms part of the minimal AAA consensus sequence that serves as a signature of this large protein family. Analysis of recombinant Sec18-109p indicates that the mutation does not prevent hexamerization or interaction with yeast alpha-SNAP (Sec17p), but instead results in undetectable ATPase activity that cannot be stimulated by Sec17p. This suggests a role for the AAA protein consensus sequence in regulating ATP hydrolysis. Furthermore, this approach of screening for dominant negative mutants in yeast can be applied to other conserved proteins so as to highlight important functional domains in their mammalian counterparts.

Adenosine Triphosphatases↗

Quantifying patient preferences for out-of-hours primary care.

OBJECTIVE: To quantify public preferences for different attributes of out-of-hours primary medical care. METHODS: This study applies a technique called conjoint analysis. A focus group was convened to identify the most important attributes for inclusion in the study, followed by a postal questionnaire asking people to choose between hypothetical services containing different mixes of these attributes. Multi-variate regression analysis estimated the relative importance of different attributes to respondents. The respondents were 436 adults who were among respondents to an earlier postal survey of 25,090 randomly selected Sheffield residents. RESULTS: The doctor's manner (whether the doctor takes time to listen), the type of consultation (whether the patient receives a home visit, telephone advice, sees an accident and emergency doctor or attends a primary care treatment centre) and waiting time for consultation best predicted the public's preferences for out-of-hours care. Another three attributes--ease of access; seeing a familiar doctor; and the doctor's shift arrangements--were not statistically significant. CONCLUSIONS: By asking people to make simple choices between hypothetical services, it is possible to quantify their strength of preference for different aspects of a service. This has important implications for the planning of services. Specifically, for out-of-hours services, more consideration should be given to the doctor's manner and waiting times rather than familiarity of doctor.

Data Interpretation, Statistical↗

Palliative care nursing in rural Western Australia.

This article presents the findings of a study of rural palliative care nurses in Western Australia. The number of rural centres in Western Australia offering palliative care services is increasing; however, at present there is little empirical data available about the roles of the nurses involved. This study was undertaken to begin to correct this deficit. The study examined basic social processes associated with the role of rural palliative care nurses, and identifies issues that affect the nurses' professional practice. A modified grounded theory approach was used to form a conceptual framework that describes rural palliative care nursing. Theoretical sampling techniques were used to identify the six palliative care nurses working in rural Western Australia who participated in the study. Data were generated using in-depth interview and participant observation techniques. Constant comparative analysis of the data was employed to allow concepts to emerge from the data. The central theme that developed is the all-consuming nature of the rural palliative care nurse's role. Three subthemes relating to multiple roles, expectations of nurses, and coping strategies are also discussed. This research explored issues that rural palliative care nurses feel are relevant to their professional practice, and it describes the basic social processes inherent in the rural palliative care nurse's role. Recommendations for nursing research, education, administration and clinical practice are presented.

Adaptation, Psychological↗

Costs and benefits of community postnatal support workers: a randomised controlled trial.

OBJECTIVES: This study aimed to measure the effect and the total cost per woman of providing postnatal support at home, based on a Dutch model. The research hypothesis was furnished by some existing evidence that postnatal support could reduce the risk of postnatal depression and encourage breastfeeding. DESIGN: The randomised controlled trial aimed to measure differences in health status in a group of women who were offered postnatal support from a community midwifery support worker (SW) compared with a control group of women who were not offered this support. Women were followed-up by postal questionnaire at 6 weeks and 6 months postnatally. SETTING AND SUBJECTS: All women who delivered a baby at the recruiting hospital were eligible to take part in the trial if they lived within the study area, were aged 17 years or over, and could understand English. INTERVENTION: The intervention consisted of the SW offering practical and emotional support and to help women rest and recover after childbirth. The SW offered ten visits in the first 28 days postnatally, for up to 3 hours per day. The SW's activities included housework, talking with the mother, and care for the baby or other siblings. The service was provided in addition to routine visits by the community midwife. MAIN OUTCOME MEASURES: The primary outcome was the general health perception domain of the Short Form-36 at 6 weeks. Secondary outcomes were mean Edinburgh Postnatal Depression Scale (EPDS), Duke Functional Social Support (DUFSS) scores and breastfeeding rates. RESULTS: The 623 randomised women were well-matched by group with a good response to follow-up. At 6 weeks there was no evidence of a significant difference between the two groups for the primary outcome. There was a non-significant trend for the control group to have better mean DUFSS and EPDS scores at 6 weeks. Breastfeeding rates were not significantly different at follow-up. At 6 months, both groups had similar health status. Satisfaction with the service was higher than for all other services received. The incremental cost of introducing the service comprised setting up and running the service. There were no differences between the groups in other resource use (general practitioner contacts, hospital services, prescriptions or medicines bought for mothers and babies) to 6-month follow-up. The total mean NHS cost to 6-month follow-up for the intervention group was pound180 per woman greater than for the control group (confidence interval, pound79.60, pound272.40). CONCLUSIONS: Although women valued the service, there was no evidence of any health benefit at the 6-week or 6-month follow-up, no difference in use of NHS services, and the additional cost of the service provision would be around pound 180 per woman.

Adolescent↗

nSec-1 (munc-18) interacts with both primed and unprimed syntaxin 1A and associates in a dimeric complex on adrenal chromaffin granules.

The target-SNARE syntaxin 1A is an essential component of the core machinery required for regulated exocytosis (where SNARE is the soluble N-ethylmaleimide-sensitive fusion protein-attachment protein receptor). Syntaxin 1A interacts with a variety of other proteins, two of which, N-ethylmaleimide-sensitive fusion protein (NSF) and alpha-soluble NSF attachment protein (alpha-SNAP) have been suggested to impart a conformational rearrangement on this protein during a reaction referred to as priming. We have studied the effect of the primed state on the binding properties of syntaxin 1A and we have confirmed that primed syntaxin 1A no longer associated with alpha-SNAP or its cognate vesicle-SNARE, vesicle-associated membrane protein (VAMP). Under such conditions, however, it retained the ability to bind to nSec-1. It has been demonstrated that nSec-1, a regulatory protein also involved in neuronal exocytosis, binds syntaxin 1A with high affinity in vitro, although evidence for this physical interaction occurring in vivo has proven elusive. We analysed the subcellular distribution of these two proteins in fractions from bovine adrenal medulla and detected syntaxin 1A and nSec-1 in both plasma membrane and chromaffin-granule fractions. Using a cross-linking approach with chromaffin-granule membranes we detected a putative dimeric complex composed of approx. 54% total granule membrane nSec-1 and approx. 30% total syntaxin 1A. The results of this study therefore suggest the possibility of nSec-1 interactions with primed syntaxin 1A and demonstrate a potentially significant interaction of syntaxin 1A and nSec-1 on the membranes of chromaffin granules.

Adrenal Medulla↗

The isoprostane, 8-epi-PGF2 alpha, is accumulated in coronary arteries isolated from patients with coronary heart disease.

OBJECTIVE: In the present study we wanted to know whether 8-epi-PGF2 alpha, which belongs to the class of isoprostanes formed by free radical-mediated peroxidation of arachidonic acid and arachidonyl-containing phospholipids, is enriched in isolated coronary arteries of patients suffering from coronary heart disease (CHD, n = 23) who received allograft heart transplants as compared to vessels derived from patients with dilative cardiomyopathy (CMP, n = 19) or from healthy heart donors (controls, n = 6). METHODS: Sections from the isolated coronary arteries were analysed by semiquantitative immunohistochemistry by determining the area and intensity of positive reaction for 8-epi-PGF2 alpha in the vascular intima and media. In addition, the 8-epi-PGF2 alpha content was determined using a specific immunoassay after extraction and purification. RESULTS: The immunohistochemical results indicated that 8-epi-PGF2 alpha is significantly enriched in arteries from patients suffering from CHD as compared to CMP (P < 0.0001). In controls, significantly less immunostaining was observed. Furthermore, a significant positive correlation between semiquantitative immunohistochemistry and radioimmunological determination was observed too. CONCLUSIONS: From our findings we conclude that 8-epi-PGF2 alpha is especially accumulated in coronary arteries from CHD patients and therefore is likely to be involved in atherogenesis.

Analysis of Variance↗

Biochemical analysis of the Saccharomyces cerevisiae SEC18 gene product: implications for the molecular mechanism of membrane fusion.

The SEC18 gene product is 48% identical to mammalian NSF (N-ethylmaleimide-sensitive fusion protein), and both proteins encode cytoplasmic ATPases which are essential for membrane traffic in yeast and mammalian cells, respectively. A wealth of biochemical analysis has led to the description of a model for the action of NSF; through its interaction with SNAPs (soluble NSF attachment proteins), NSF can associate with SNAP receptors (SNAREs) on intracellular membranes, forming 20S complexes. SNAPs then stimulate the intrinsic ATPase activity of NSF, leading to the disassembly of the 20S complex, which is essential for subsequent membrane fusion. Although this model is based almost entirely on in vitro studies of the original clones of NSF and alpha-SNAP, it is nevertheless widely assumed that this mechanism of membrane fusion is conserved in all eukaryotic cells. If so, the crucial biochemical properties of NSF and SNAPs should be shared by their yeast homologues, Sec18p and Sec17p. Using purified recombinant proteins, we report here that Sec18p can specifically interact not only with Sec17p but also with its mammalian homologue, alpha-SNAP. This interaction leads to a stimulation of Sec18p D1 domain ATPase activity, with kinetics similar to those of alpha-SNAP stimulation of NSF, although differences in temperature and N-ethylmaleimide sensitivity were observed between NSF and Sec18p. Furthermore, Sec18p can interact with synaptic SNARE proteins and can synergize with alpha-SNAP to stimulate regulated exocytosis in mammalian cells. We conclude that the mechanistic properties of NSF and SNAPs are shared by Sec18p and Sec17p, thus demonstrating that the biochemistry of membrane fusion is conserved from yeast to mammals.

Adenosine Triphosphatases↗

No association between D2 dopamine receptor (DRD2) "A" system alleles, or DRD2 haplotypes, and posttraumatic stress disorder.

BACKGROUND: Association studies between marker alleles at the D2 dopamine receptor gene (DRD2) and various psychiatric illnesses have produced conflicting results. Reports of allelic associations were originally made with alcoholism, but were then extended to other psychiatric disorders, including posttraumatic stress disorder (PTSD). METHODS: We studied allele frequency of the DRD2 TaqI "A," "B," and "D" system markers in 52 European-American subjects with diagnoses of PTSD (based on structured interviews). RESULTS: Frequency of the A1 allele in this sample was .15, not significantly different from the .19 allele frequency seen in 87 control subjects. We were thus unable to replicate the previous reports of allelic association between the DRD2 TaqI "A1" allele and PTSD. There were also no significant differences in allele frequency for the "B" or "D" systems. We then computed three marker (TaqI "A," "B," and "D" system) haplotypes for the sample; DRD2 haplotype frequencies also did not differ between control subjects and subjects with PTSD. CONCLUSIONS: We conclude that DRD2 alleles are not associated with PTSD in this sample, and that genetic variation at the DRD2 locus is not likely to be an important contributor to risk for this disorder.

Adult↗