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Biomedical subjects

A Schofield

Publications and source records attributed to A Schofield.

At least 19 recordsLinked to original sources
PubMed2001

Nonselective versus selective beta-adrenergic receptor blockade in congestive heart failure: differential effects on sympathetic activity.

BACKGROUND: Activation of the sympathetic nervous system has important prognostic implications in chronic heart failure. Nonselective versus selective beta-adrenergic receptor antagonists may have differential effects on norepinephrine release from nerve terminals mediated by prejunctional beta(2)-adrenergic receptors. METHODS AND RESULTS: Thirty-six patients with chronic heart failure were randomized to the nonselective beta-blocker carvedilol or the selective beta-blocker metoprolol (double-blind). Measurements of hemodynamics and cardiac and systemic norepinephrine spillover as well as microneurographic recordings of muscle sympathetic nerve traffic were made before and after 4 months of therapy. In the carvedilol group (n=17), there were significant reductions in both total body (-1.7+/-0.5 nmol/min, P<0.01) and cardiac norepinephrine spillover (-87+/-29 pmol/min, P<0.01). By contrast, in the metoprolol group (n=14), there were no significant changes in total body or cardiac norepinephrine spillover. Responses in the carvedilol group were significantly different from those observed in the metoprolol group (P<0.05). Both agents caused a reduction in heart rate and increases in pulse pressure, although mean arterial pressure did not change. Importantly, microneurographic measures of sympathetic nerve traffic to skeletal muscle did not change in either group. CONCLUSIONS: Therapy with carvedilol caused significant decreases in systemic and cardiac norepinephrine spillover, an indirect measure of norepinephrine release. Such changes were not observed in patients treated with metoprolol. There was no effect of either agent on sympathetic efferent neuronal discharge to skeletal muscle. These findings suggest that carvedilol, a nonselective beta-blocker, caused its sympathoinhibitory effect by blocking peripheral, prejunctional beta-adrenergic receptors.

Adolescent↗
PubMed2001

Real-space imaging of nucleation and growth in colloidal crystallization.

Crystallization of concentrated colloidal suspensions was studied in real space with laser scanning confocal microscopy. Direct imaging in three dimensions allowed identification and observation of both nucleation and growth of crystalline regions, providing an experimental measure of properties of the nucleating crystallites. By following their evolution, we identified critical nuclei, determined nucleation rates, and measured the average surface tension of the crystal-liquid interface. The structure of the nuclei was the same as the bulk solid phase, random hexagonal close-packed, and their average shape was rather nonspherical, with rough rather than faceted surfaces.

Journal Article↗
PubMed2001

Breaking the silence: women living with multiple sclerosis and urinary incontinence.

This study examined women's understandings of living with multiple sclerosis (MS) and urinary incontinence and the challenges they have encountered in their day-to-day lives. As health-care professionals, we aimed to understand how people living with MS manage urinary incontinence. This paper reports the findings from a Participatory Action Research (PAR) group with four women, the researcher and two Continence Nurse Advisors (CNAs). The group met on five occasions between March and June 1999. The women's stories held personal and gendered meanings about living with MS and urinary incontinence. Four themes were derived from the transcripts: maintaining control; seeking understanding; avoiding shame; and good and bad days. The women and the CNAs benefited from an exchange of knowledge about living with MS and incontinence. The CNAs became sensitive to the women's experience and have been able to incorporate these understandings into their practice. By sharing our research we hope the findings may be more widely incorporated into sensitive health practice.

Adaptation, Psychological↗
PubMed2001

Pelvic floor reeducation for stress incontinence: comparing three methods.

Stress urinary incontinence is a common problem among women of all ages but may resolve with pelvic floor reeducation in many cases. Compliance to a regimen of pelvic floor muscle exercises is poor and many devices have been produced to make exercising these muscles more effective and interesting. This article describes a study in which two such devices -- vaginal cones and pressure biofeedback -- were compared with pelvic floor exercises alone. The results show that there is no statistically significant difference between the three modalities; all treatments produced significant improvement in symptoms and quality of life scores.

Adult↗
PubMed2001

Oophorectomy in primary colorectal cancer.

Colorectal cancer is a common cancer affecting women which may metastasize to the ovaries. We present five cases of ovarian metastases requiring surgery and review the debate regarding oophorectomy at the primary resection for colorectal cancer. Although prophylactic oophorectomy has not been proven to affect survival, further surgery for symptomatic ovarian metastases may be avoided and the increased risk of developing primary ovarian cancer is abolished.

Adult↗
PubMed2000

Entropically driven colloidal crystallization on patterned surfaces

We investigate the self-assembly of colloidal spheres on periodically patterned templates. The surface potentials and the surface phases are induced entropically by the presence of dissolved, nonadsorbing polymers. A rich variety of two-dimensional fluidlike and solidlike phases was observed to form on template potentials with both one- and two-dimensional symmetry. The same methodology was then used to nucleate an oriented single fcc crystal more than 30 layers thick. The general approach provides a new route for directed self-assembly of novel mesoscopic structures.

Journal Article↗
PubMed2000

Three-dimensional direct imaging of structural relaxation near the colloidal glass transition

Confocal microscopy was used to directly observe three-dimensional dynamics of particles in colloidal supercooled fluids and colloidal glasses. The fastest particles moved cooperatively; connected clusters of these mobile particles could be identified; and the cluster size distribution, structure, and dynamics were investigated. The characteristic cluster size grew markedly in the supercooled fluid as the glass transition was approached, in agreement with computer simulations; at the glass transition, however, there was a sudden drop in their size. The clusters of fast-moving particles were largest near the alpha-relaxation time scale for supercooled colloidal fluids, but were also present, albeit with a markedly different nature, at shorter beta-relaxation time scales, in both supercooled fluid and glass colloidal phases.

Journal Article↗
PubMed1998

Haplotype and phenotype analysis of nine recurrent BRCA2 mutations in 111 families: results of an international study.

Several BRCA2 mutations are found to occur in geographically diverse breast and ovarian cancer families. To investigate both mutation origin and mutation-specific phenotypes due to BRCA2, we constructed a haplotype of 10 polymorphic short tandem-repeat (STR) markers flanking the BRCA2 locus, in a set of 111 breast or breast/ovarian cancer families selected for having one of nine recurrent BRCA2 mutations. Six of the individual mutations are estimated to have arisen 400-2,000 years ago. In particular, the 6174delT mutation, found in approximately 1% of individuals of Ashkenazi Jewish ancestry, was estimated to have arisen 29 generations ago (1-LOD support interval 22-38). This is substantially more recent than the estimated age of the BRCA1 185delAG mutation (46 generations), derived from our analogous study of BRCA1 mutations. In general, there was no evidence of multiple origins of identical BRCA2 mutations. Our study data were consistent with the previous report of a higher incidence of ovarian cancer in families with mutations in a 3.3-kb region of exon 11 (the ovarian cancer cluster region [OCCR]) (P=.10); but that higher incidence was not statistically significant. There was significant evidence that age at diagnosis of breast cancer varied by mutation (P<.001), although only 8% of the variance in age at diagnosis could be explained by the specific mutation, and there was no evidence of family-specific effects. When the age at diagnosis of the breast cancer cases was examined by OCCR, cases associated with mutations in the OCCR had a significantly older mean age at diagnosis than was seen in those outside this region (48 years vs. 42 years; P=.0005).

Adult↗
PubMed1996

Regulation of the double-stranded RNA-dependent protein kinase PKR by RNAs encoded by a repeated sequence in the Epstein-Barr virus genome.

During the initial infection of B lymphocytes by Epstein-Barr virus (EBV) only a few viral genes are expressed, six of which encode the EBV nuclear antigens, EBNAs 1-6. The majority of EBNA mRNAs share common 5'-ends containing a variable number of two alternating and repeated exons transcribed from the BamHI W major internal repeats of the viral DNA. These sequences can also exist as independent small RNA species in some EBV-infected cell types. We present evidence that transcripts from these W repeat regions can exert a trans-acting effect on protein synthesis, through their ability to activate the dsRNA-dependent protein kinase PKR. UV cross-linking and filter binding assays have demonstrated that the W transcripts bind specifically to PKR and can compete with another EBV-encoded small RNA, EBER-1, which was shown previously to bind this kinase. In the reticulocyte lysate system the W RNAs shut off protein synthesis through an ability to activate PKR. In contrast to EBER-1, the W RNAs are unable to block the dsRNA-dependent activation of PKR. Using a purified preparation of the protein kinase we have shown that the W transcripts directly activate PKR in vitro. The results suggest that EBV has the ability both to activate and to inhibit PKR through the actions of different products of viral transcription.

Base Sequence↗
PubMed1996

Ascertainment of familial ovarian cancer in the Aberdeen Genetic Clinic.

Ovarian cancer is the fifth most common malignancy in women in the UK. Patients with a family history including ovarian cancer make up nearly 15% of family cancer referrals to the Genetic Clinic in Aberdeen. To date, only one pedigree has been suitable for linkage studies, which has enabled us to target screening more accurately at those people at highest risk. Following discovery of a strong candidate for the BRCA1 gene, direct mutation testing may soon be possible. People who seek testing will require further counselling. Therefore we anticipate an increased demand on both clinical and laboratory resources, but more accurate ascertainment of high risk subjects should lead to more appropriate targeting of screening services.

Adult↗
PubMed1994

Regulation of the interferon-inducible eIF-2 alpha protein kinase by small RNAs.

This review describes the structure and function of the double-stranded RNA-dependent protein kinase (PKR) and its interaction with RNA activators and inhibitors. The abilities of small virally-encoded RNAs such as VAI RNA of adenovirus, the Epstein-Barr virus encoded (EBER) RNAs and the Tat-responsive region RNA of HIV-1 to bind to and regulate PKR are reviewed, and the physiological implications of such regulation for the control of viral replication and cell growth are discussed. The potential effects on the activity of PKR of other proteins that bind double-stranded RNA and/or small viral and cellular RNAs are also considered.

Adenoviridae↗
PubMed1993

Providing a personal service in the Trent Region.

Reports evaluation of the Trent Regional Health Authority's "Providing a Personal Service" initiative, one of the first major quality management strategies in the NHS. The evaluation highlights the key elements which supported this initiative and suggests some ways in which its progress can be sustained. Many of the comments are applicable to other approaches to quality management.

England↗
PubMed1987

Neurologic referrals to a psychiatric consultation-liaison service. A study of 199 patients.

The findings in a 199 neurology patients referred to a psychiatric consultation-liaison service are analyzed. Neurology referrals differ from general hospital referrals in reasons for referral and in patterns of diagnosis. The most common conversion symptoms seen are pain and pseudoseizures. The psychiatric diagnosis made in those patients with functional pain varies with the site of the pain. These two conversion symptoms, pain and pseudoseizures, have differing ages of onset and prognoses. A number of patients were given no psychiatric diagnosis and the reasons for this are discussed. The incidence of various neurologic diagnoses made in those patients referred to the consultation-liaison service is compared with the incidence of those diagnoses made in consecutive admissions to the neurology ward.

Adolescent↗