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Biomedical subjects

B Clarke

Publications and source records attributed to B Clarke.

At least 73 records · Page 4Linked to original sources
PubMed1997

The role of urodynamic assessment in the diagnosis of lower urinary tract disorders.

The relationship between clinical symptomatology and urodynamic findings was studied prospectively in 1000 unselected women with symptoms of lower urinary tract dysfunction. Women in the study were subjected to both clinical and multichannel urodynamic assessment. The symptom of stress incontinence was confirmed by urodynamic assessment to be associated with genuine stress incontinence (95%). However, it was also associated with sensory urgency (96%) and detrusor instability (64%). Other lower urinary tract symptoms were associated with a range of abnormal urodynamic findings. It was concluded that urodynamic assessment provided useful information in women with lower urinary tract disorders, in developing principles of diagnosis and management.

Female↗
PubMed1997

The purpose of flexible learning in post-registration nurse education.

Post-registration nurse education in England has changed significantly in recent years. One of the most significant changes has been the emergence of flexible learning which is characterized by adaptations in the way programmes are planned, the nature of provision, the ways of enhancing access, the process of teaching and learning, the nature of assessment and the way in which programmes are evaluated. This paper reviews the influences on nurse education at post-registration level which have brought about flexible learning. It analyses the purposes of flexible learning by integrating theoretical considerations and the outcomes of the case study of programmes and modules deemed by providers to be flexible. The over-arching purpose of flexible learning is the improvement of educational quality, specifically in relation to improving access, availability, relevance, and the way in which individual practitioners' needs and importantly the needs of other stakeholders (for example, providers, employers and validating bodies) are met. Flexible learning is also concerned with encouraging self-direction in professional learning. The different purposes and the way in which they interrelate, together with the range of different stakeholders and their potentially conflicting needs, significantly complicates the management of flexible learning.

Curriculum↗
PubMed1997

Outcome of pregnancy in women with Marfan's syndrome.

OBJECTIVE: To improve life expectancy and prevent premature mortality in women with Marfan's syndrome. METHODS: During the development of a regional genetic register for Marfan's Syndrome the outcome of 91 pregnancies in 36 women with this condition was established retrospectively and the cardiovascular and obstetric complications documented. RESULTS: No patient had a significant cardiovascular abnormality limiting function before her pregnancy. Of 36 women, four had an aortic dissection relating to pregnancy and two others required aortic surgery following delivery. Thirty women had uncomplicated gestational histories. The incidence of obstetric complications did not exceed expectation. CONCLUSIONS: Women with Marfan's syndrome are at significant risk of aortic dissection in pregnancy even in the absence of preconceptional cardiovascular abnormality. Aortic root dilatation may be a predictor of risk but dissection may occur without significant dilatation. Guidelines for obstetric care are suggested and preconceptional assessment recommended.

Adult↗
PubMed1996

Structural requirements for initiation of translation by internal ribosome entry within genome-length hepatitis C virus RNA.

Cap-independent translation of hepatitis C virus (HCV) RNA is mediated by an internal ribosomal entry segment (IRES) located within the 5' nontranslated RNA (5'NTR), but previous studies provide conflicting views of the viral sequences which are required for translation initiation. These discrepancies could have resulted from the inclusion of less than full-length 5'NTR in constructs studied for translation or destabilization of RNA secondary structure due to fusion of the 5'NTR to heterologous reporter sequences. In an effort to resolve this confusion, we constructed a series of mutations within the 5'NTR of a nearly full-length 9.5-kb HCV cDNA clone and examined the impact of these mutations on HCV translation in vitro in rabbit reticulocyte lysates and in transfected Huh-T7 cells. The inclusion of the entire open reading frame in HCV transcripts did not lead to an increase in IRES-directed translation of the capsid and E1 proteins, suggesting that the nonstructural proteins of HCV do not include a translational transactivator. However, in reticulocyte lysates programmed with full-length transcripts, there were multiple aberrent translation initiation sites resembling those identified in some picornaviruses. The deletion of nucleotides (nt) 28-69 of the 5'NTR (stem-loop IIa) sharply reduced capsid translation both in vitro and in vivo. A small deletion mutation involving nt 328-334, immediately upstream of the initiator AUG at nt 342, also resulted in a nearly complete inhibition of translation, as did the deletion of multiple intervening structural elements. An in-frame 12-nt insertion placed within the capsid-coding region 9 nt downstream of the initiator AUG strongly inhibited translation both in vitro and in vivo, while multiple silent mutations within the first 42 nt of the open reading frame also reduced translation in reticulocyte lysates. Thus, domains II and III of the 5'NTR are both essential to activity of the IRES, while conservation of sequence downstream of the initiator AUG is required for optimal IRES-directed translation.

Amino Acid Sequence↗
PubMed1996

A Markov model for the assembly of heterochromatic regions in position effect variegation.

Here we give a mathematical model for the assembly of heterochromatic regions at the heterochromatin-euchromatin interface in position effect variegation. This probabilistic model predicts the proportions of cells in which a gene is active in cells with one and two variegating chromosomes. The association of heterochromatic proteins to form remodeled chromatin following DNA replication is mainly described by accumulation independent conditional probabilities. These probabilities are conditional on the boundary of the sites to which the proteins can bind; they give the relative attractiveness of the sites to a protein complex chosen at random from a pool of available complexes. The number of complexes available is assumed to be limited and rates of reaction are implicitly modeled by the conditional probabilities. In general, these conditional probabilities are not known, however, they can be experimentally determined. By comparing double variegation situations to single variegation, this model shows that there may be an effect on the expression of reporter genes located near the interfaces due to different sites competing for heterochromatic proteins. In addition, this model suggests that in some cases the attractiveness of sites may change in the presence of other chemical species. Consequently, the model distinguishes between two sorts of data obtained from competition experiments using position effect variegation. The two sorts of data differ as to whether there is a change in the attractiveness of sites in addition to an effect from different sites competing for the same constituents of heterochromatin. Subject to the fact that some of its parameters are not known precisely, this model replicates data from several experiments and can give predictions in other cases.

Animals↗
PubMed1996

Extreme divergence of mitochondrial DNA within species of pulmonate land snails.

Mitochondrial DNA, inherited predominantly through the female line, has been exceptionally useful for reconstructing phylogenies (Avise, in Molecular markers, natural history and evolution. New York: Chapman and Hall (1994)). However, at the lowest taxonomic level, if there are polymorphisms within species the lineages of mitochondria need not correspond to the lineages of the species (Avise, in Phil. Trans. R. Soc. Lond. B 312, 325-342 (1986)). We find that a classic organism in ecological genetics, Cepaea nemoralis, has the most extreme intraspecific variation and polymorphism so far recorded, and that at least one other pulmonate land mollusc also has very high levels of mitochondrial diversity. Making the simplest assumptions, the data suggest times of divergence as long ago as 20 million years between haplotypes now coexisting within a single population. There are four overlapping explanations of the diversity: (i) that mitochondrial evolution in pulmonates is exceptionally fast; (ii) that the morphs have differentiated in isolated 'refuges' and then come together; (iii) that natural selection has acted to preserve the variation; and (iv) that the population structure of pulmonates favours the persistence of ancient haplotypes. We argue for the importance of the last explanation.

Animals↗
PubMed1996

On the roles of long-chain acyl carnitine accumulation and impaired glucose utilization in ischaemic contracture development and tissue damage in the guinea-pig heart.

It has been proposed that the presence of increasing concentrations of fatty acids may accelerate the development of ischaemic contracture and cardiac damage, and that this may be due to long-chain acyl carnitine accumulation and/or impairment of glucose utilization. In isolated guinea-pig papillary muscles, palmitoyl (DL) carnitine was found to have a positive inotropic effect, with a slow onset of action suggestive of an intracellular site of action, and with a maximal effect of about two-fold at a concentration of 5-10 microM; higher concentrations led to decreased contraction, probably due to increasing detergent-like effects. In isolated fura-2-loaded chick cardiomyocytes, palmitoyl carnitine increased intracellular [Ca2+]; it is proposed that this is the means by which it increases contraction. The main hypothesis above was studied using isolated guinea-pig hearts perfused with either 11.7 mM or 5 mM glucose, and either albumin alone (3%) or albumin bound palmitate (1.5 mM) during low-flow ischaemia (92% reduction in flow) for up to 60 min. With 11.7 mM glucose, the presence of palmitate caused contracture development and increased enzyme release during ischaemia. Contracture also developed when the glucose concentration was reduced to 5 mM in the absence of fatty acid, however, in its presence contracture developed to a greater extent and with increased enzyme release. Long-chain acyl carnitine accumulation was similar in both groups. These studies show that long-chain acyl carnitine accumulation has the potential to induce contracture during ischaemia, although a reduction in glucose availability may also contribute.

Animals↗
PubMed1996

Ranolazine increases active pyruvate dehydrogenase in perfused normoxic rat hearts: evidence for an indirect mechanism.

Ranolazine has shown anti-anginal efficacy in humans and cardiac anti-ischaemic activity in models, but without affecting haemodynamics or baseline contraction. In isolated normoxic rat hearts, Langendorff-perfused for 30 min with 11 mM glucose, 3% albumin, and 0.4 mM or 0.8 mM palmitate, 20 microM ranolazine significantly increased active, dephosphorylated, pyruvate dehydrogenase (PDHa), but not with no palmitate or 1.2 mM palmitate. Dichloroactetate (DCA, 1 mM), a PDHa kinase inhibitor, significantly increased PDHa in hearts perfused with 0, 0.4 or 0.8 mM but not 1.2 mM palmitate. PDHa was significantly increased with 1.2 mM palmitate by DCA plus ranolazine, and additive effects were also seen at 0.8 mM palmitate. Activation of PDH by ranolazine and promotion of glucose oxidation offers a plausible means by which the drug may be anti-ischaemic nonhaemodynamically. Extensive studies with extracted enzymes and isolated rat heart mitochondria failed to demonstrate any effects of ranolazine on PDH kinase or phosphatase, or on PDH catalytic activity, whereas effects of other known effectors (such as DCA) were readily demonstrable, suggesting that ranolazine activates PDH indirectly. Further analyses of the hearts revealed that ranolazine reduced acetyl CoA content under all conditions where fatty acid was present, and +/- DCA which itself had little effect. In the absence of fatty acid, ranolazine and/or DCA raised acetyl CoA. In perfusions where octanoate (+/- albumin) replaced palmitate, ranolazine still decreased acetyl CoA, but not when acetate replaced palmitate. In octanoate-perfused hearts, the contents of the C4, C6 and C8 CoA esters were all increased by ranolazine. This is consistent with ranolazine causing an inhibition of fatty acid beta-oxidation leading to decreased acetyl CoA and activation of PDH.

Acetanilides↗
PubMed1996

Anticholinergic medication for the unstable bladder: prospective trials of imipramine/propantheline versus penthienate and oxybutynin versus penthienate.

A comparison was made of three drug regimens: imipramine (Tofranil)/propantheline, oxybutynin (Ditropan) and penthienate bromide (Monodral). Two comparative trials were performed in prospective studies, using a randomization and cross-over design. All the drugs were found to improve the urinary symptoms and urodynamic changes associated with the unstable bladder, but penthienate was shown to be more effective than imipramine/propantheline. Its effect on the unstable bladder was equivalent to that of oxybutynin. Side-effects were common and most common with oxybutynin. However, the inability of these drugs to prevent the uninhibited detrusor contractions of the unstable bladder consistently and objectively was demonstrated.

Adrenergic Uptake Inhibitors↗
PubMed1996

Reflective practice: reviewing the issues and refocusing the debate.

Reflective practice has emerged in the U.K. and beyond as an important issue not just in nursing but in many other professions. However, it remains problematic; it is difficult to conceptualize and many aspects of it are open to debate. Reflective practice is also contentious because, at a fundamental level, it raises a number of important issues for professional practitioners and the way they view their practice. The intention of this paper is to: explore some of the issues that have emerged as the profession of nursing and other professions have gained a better understanding of reflective practice; broaden the scope of the debate and refocus it; raise issues which are in need of further research.

Holistic Nursing↗
PubMed1996

Chimeric hepatitis B virus core particles as probes for studying peptide-integrin interactions.

An RGD-containing epitope from the foot-and-mouth disease virus (FMDV) VP1 protein was inserted into the e1 loop of the hepatitis B virus core (HBc) protein. This chimeric protein was expressed at high levels in Escherichia coli and spontaneously assembled into virus-like particles which could be readily purified. These fusion particles elicited high levels of both enzyme-linked immunosorbent assay- and FMDV-neutralizing antibodies in guinea pigs. The chimeric particles bound specifically to cultured eukaryotic cells. Mutant particles carrying the tripeptide sequence RGE in place of RGD and the use of a competitive peptide, GRGDS, confirmed the critical involvement of the RGD sequence in this binding. The chimeric particles also bound to purified integrins, and inhibition by chain-specific anti-integrin monoclonal antibodies implicated alpha 5 beta 1 as a candidate cell receptor for both the chimeric particle and FMDV. Some serotypes of FMDV bound to beta 1 integrins in solid- phase assays, and the chimeric particles competed with FMDV for binding to susceptible eukaryotic cells. Thus, HBc particles may provide a simple, general system for exploring the interactions of specific peptide sequences with cellular receptors.

Animals↗
PubMed1996

Colonoscopy evaluations: justification by cost?

The type of colonic imaging (radiological vs colonoscopic) for evaluating symptomatic patients without evidence of bleeding in both an efficacious and cost-conserving manner has become a very debated issue. In a randomized, controlled clinical trial, the authors hoped to examine the prevalence of neoplasm and the effectiveness and cost-effectiveness of initial diagnostic strategies of colonoscopy versus flexible sigmoidoscopy and air contrast barium enema in patients without evidence of intestinal bleeding. One hundred forty-nine patients over the age of 40 with symptoms suggestive a colonic disease without evidence of bleeding (no hematechezia, negative test for fecal occult blood, and normal serum hemoglobin) were randomized to undergo either initial colonoscopy or flexible sigmoidoscopy plus barium enema. Patients with incomplete lower GI tests were referred for the corresponding alternative imaging modality. Cost analyses using sensitivity analysis were performed. Baseline information with respect to age, race, sex, inpatient status, reason for referral, mean weight loss, hemoglobin, blood urea nitrogen, and albumin were similar in both groups. Eighteen patients (24%) who initially received air contrast barium enema and flexible sigmoidoscopy then required colonoscopy, whereas only five patients (6%) who initially underwent colonoscopy first required air contrast barium enema plus flexible sigmoidoscopy. The study found that: a) The prevalence of cancer in the study was low (one of 149 patients); b) initial colonoscopy detected more persons with adenomas than that of air contrast barium enema plus flexible sigmoidoscopy (23 of 75 patients vs 13 of 74 patients, odds radio, 2.07, CI,0.90-4.92; this approached significance); and c) air contrast barium enema plus flexible sigmoidoscopy detected more diverticulosis (46 of 74 patients vs 31 of 75 patients, odds ratio, 0.41, 95% CI, 0.21-0.87). The significant conclusions were that patients undergoing flexible sigmoidoscopy plus air contrast barium enema were more likely to undergo alternative procedures and that sensitivity analysis suggested that, for most areas in the United States, initial colonoscopy would be more cost-effective for the outcome of detection of adenomas (1).

Barium Sulfate↗
PubMed1995

An infectious cDNA clone of a cytopathic hepatitis A virus: genomic regions associated with rapid replication and cytopathic effect.

Rapidly replicating, cytopathic (rr/cpe+) variants of hepatitis A virus (HAV) isolated from persistently infected BS-C-1 cells have numerous mutations from cell culture-adapted rr/cpe- HAV. To determine which mutations in one rr/cpe+ virus, HM175/18f, determine enhanced replication in BS-C-1 cells, a series of chimeric viruses was rescued from infectious cDNAs in which HM175/18f genomic segments were placed within the background of a related rr/cpe- virus, HAV/7. Chimeric viruses containing the P2 region of HM175/18f produced replication foci in BS-C-1 cells that were larger than HAV/7, but not as large as HM175/18f virus. Enhanced viral replication required mutations in both 2B and 2C proteins, suggesting that these proteins remain closely associated during replication. Mutations in 5' nontranslated RNA (5'NTR) or P3 proteins had no independent effect, but acted cooperatively with mutations in P2 proteins to enhance replication and render the virus capable of conventional plaque formation. Cytopathic effects correlated with viral replication capacity and were not the result of any single mutation. Full expression of the rr/cpe+ phenotype required mutations within the 5'NTR, P2, and P3 segments. These results suggest novel interactions between the 5'NTR and P2 proteins during HAV replication and provide useful new infectious cDNA clones.

Animals↗
PubMed1995

Protection by attenuated simian immunodeficiency virus in macaques against challenge with virus-infected cells.

A vaccine against AIDS will probably have to protect against challenge both by viable virus-infected cells and by cell-free virus. Eight cynomolgus macaques infected with attenuated simian immunodeficiency virus (SIV) were challenged (four each) with cell-free and cell-associated SIV. All were protected, whereas eight controls were all infected after challenge. These findings show that live-attenuated vaccine can confer protection against SIV in macaques. Extrapolation to human beings will require extensive evaluation of the safety of attenuated retroviruses. Alternatively, the mechanism of this potent protection must be understood and reproduced by less hazardous means.

AIDS Vaccines↗