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Biomedical subjects

S Davies

Publications and source records attributed to S Davies.

At least 145 records · Page 8Linked to original sources
PubMed1999

Facilitating learning in the community with lecturer-practitioner posts.

The purpose of this paper is to present a case study of the perspectives of their role of a group of community lecturer-practitioners and a community teacher, who referred to themselves as 'community facilitators'. A qualitative design was used and data were collected by semi-structured interviews. These were transcribed and content analysis was undertaken. All participants provided a liaison role between the college and the community practitioners, prepared students for their clinical experience and assisted in relating theory to practice. The participants described how they managed the role and how they supported each other. Developing small teams of facilitators may provide a bridge between teachers and practitioners and can serve as a basis for further study of the lecturer-practitioner role.

Adult↗
PubMed1999

Continuing education needs of community nurses, midwives and health visitors for supervising and assessing students.

The objective of this study was to ascertain the changing educational needs of community nurses, midwives and health visitors in relation to the teaching, supervising and assessing of pre- and post-registration students. A questionnaire was sent to all education institutions providing community nursing experience in England (Whittaker et al. 1997), which allowed identification of three centres for in-depth study. Questionnaires were sent to practitioners (community nurses and midwives, health visitors and school nurses), their managers, and teachers of community courses in the three centres: 314 were returned. Eight semi-structured interviews were undertaken with volunteers in each of the study centres (n = 24). Extensive demands are being made on community staff to provide learning experiences for students on a wide range of courses. Practitioners reported that in order to fulfil their teaching and assessing functions they needed continuing education in matters which would assist them to provide research-based practice and education, teaching and assessing in the community and personal skills, for example assertiveness and counselling. Less than a quarter of practitioners were undertaking continuing education courses. However, opportunities for further academic study varied enormously and most practitioners had to study in their own time at their own expense.

Clinical Competence↗
PubMed1999

Identification and characterization of a two-component sensor-kinase and response-regulator system (DcuS-DcuR) controlling gene expression in response to C4-dicarboxylates in Escherichia coli.

The dcuB gene of Escherichia coli encodes an anaerobic C4-dicarboxylate transporter that is induced anaerobically by FNR, activated by the cyclic AMP receptor protein, and repressed in the presence of nitrate by NarL. In addition, dcuB expression is strongly induced by C4-dicarboxylates, suggesting the presence of a novel C4-dicarboxylate-responsive regulator in E. coli. This paper describes the isolation of a Tn10 mutant in which the 160-fold induction of dcuB expression by C4-dicarboxylates is absent. The corresponding Tn10 mutation resides in the yjdH gene, which is adjacent to the yjdG gene and close to the dcuB gene at approximately 93.5 min in the E. coli chromosome. The yjdHG genes (redesignated dcuSR) appear to constitute an operon encoding a two-component sensor-regulator system (DcuS-DcuR). A plasmid carrying the dcuSR operon restored the C4-dicarboxylate inducibility of dcuB expression in the dcuS mutant to levels exceeding those of the dcuS+ strain by approximately 1.8-fold. The dcuS mutation affected the expression of other genes with roles in C4-dicarboxylate transport or metabolism. Expression of the fumarate reductase (frdABCD) operon and the aerobic C4-dicarboxylate transporter (dctA) gene were induced 22- and 4-fold, respectively, by the DcuS-DcuR system in the presence of C4-dicarboxylates. Surprisingly, anaerobic fumarate respiratory growth of the dcuS mutant was normal. However, under aerobic conditions with C4-dicarboxylates as sole carbon sources, the mutant exhibited a growth defect resembling that of a dctA mutant. Studies employing a dcuA dcuB dcuC triple mutant unable to transport C4-dicarboxylates anaerobically revealed that C4-dicarboxylate transport is not required for C4-dicarboxylate-responsive gene regulation. This suggests that the DcuS-DcuR system responds to external substrates. Accordingly, topology studies using 14 DcuS-BlaM fusions showed that DcuS contains two putative transmembrane helices flanking a approximately 140-residue N-terminal domain apparently located in the periplasm. This topology strongly suggests that the periplasmic loop of DcuS serves as a C4-dicarboxylate sensor. The cytosolic region of DcuS (residues 203 to 543) contains two domains: a central PAS domain possibly acting as a second sensory domain and a C-terminal transmitter domain. Database searches showed that DcuS and DcuR are closely related to a subgroup of two-component sensor-regulators that includes the citrate-responsive CitA-CitB system of Klebsiella pneumoniae. DcuS is not closely related to the C4-dicarboxylate-sensing DctS or DctB protein of Rhodobacter capsulatus or rhizobial species, respectively. Although all three proteins have similar topologies and functions, and all are members of the two-component sensor-kinase family, their periplasmic domains appear to have evolved independently.

Amino Acid Sequence↗
PubMed1999

Longitudinal variation in hepatitis C virus (HCV) viraemia and early course of HCV infection after liver transplantation for HCV cirrhosis: the role of different immunosuppressive regimens.

BACKGROUND: The role of the type of immunosuppression in the natural history of post-transplant hepatitis C virus (HCV) infection is unclear. AIMS: To evaluate the fluctuation of HCV viraemia and the early course of infection, and their relation to the type of immunosuppression in HCV transplant patients. METHODS: In 47 HCV transplant patients, serum HCV RNA levels were determined pretransplant and at one and two weeks, and three and 12 months after transplant. Initial immunosuppression was triple (cyclosporin, azathioprine, prednisolone) in 31, double (cyclosporin, prednisolone) in five, and single (cyclosporin or tacrolimus) in 11 patients. Prednisolone was withdrawn at a median of six months. RESULTS: At three months, HCV RNA levels were higher in patients with single than with triple or double initial therapy. At 12 months, HCV RNA levels correlated only with duration of prednisolone treatment and were relatively higher in patients with triple compared with single initial immunosuppression. A higher necroinflammatory activity at 12 months post-transplant was found in patients with post-transplant acute hepatitis compared with those without. Extent of fibrosis at 12 months was associated with the 12 month HCV RNA level and occurrence of post-transplant acute hepatitis. CONCLUSIONS: HCV RNA levels at three months after transplant are higher in patients treated with single initial immunosuppressive therapy, but at 12 months are higher in patients with longer duration of steroid treatment. HCV viraemia at 12 months seems to be particularly important, as its levels are strongly correlated with the severity of fibrosis.

Acute Disease↗
PubMed1999

Trace gases in breath of healthy volunteers when fasting and after a protein-calorie meal: a preliminary study.

The selected ion flow tube technique was used to quantify in breath the trace gases acetone, ammonia, ethanol, isoprene, and methanol during single exhalations while fasting and in response to feeding. Six normal volunteers were fasted for 12 h, and, after baseline breath samples were obtained, were fed a liquid protein-calorie meal to provide 0.47 g/kg of protein (Fortisip). Further breath samples were obtained at 20, 40, and 60 min, and then hourly for a further 5 h. Breath acetone concentrations fell from a maximum during fasting, reaching their nadir between 4 and 5 h. Breath ammonia concentrations fell immediately to one-half their fasting levels before a steady increase to two or three times baseline values at 5 h. There was a brief increase in breath ethanol concentrations after feeding, reflecting detectable ethanol contamination of the food. Subsequently, breath ethanol levels remained low throughout the experimental protocol. Isoprene concentrations did not change significantly, whereas changes in methanol concentrations reflected those in the ambient air. This preliminary study indicates that the selected ion flow tube technique may be used to detect changes in the trace gases present in breath and define their concentrations in the fasting and replete state. Of particular interest is the biphasic response of the breath ammonia concentration after feeding.

Adult↗
PubMed1999

Section 25 aftercare under supervision: the first eighteen months' experience.

Supervised discharge was introduced, against much professional opposition, in the Mental Health (Patients in the Community) Act 1995. All patients subject to supervised discharge (SD) in a large health district were identified by medical records departments, and the outcome of their SD on 1 October 1997, eighteen months after the legislation came into effect, was assessed. In that first eighteen months, half of the general, rehabilitation and forensic psychiatrists in the trust used SD for 22 patients. Of the 12 orders in effect for over six months, six were renewed at six months and three at one year. In spite of professional hostility and scepticism about the clinical practicalities of SD, the use of the new power has gradually increased with experience. Outcomes to date seem generally positive, but further definitive research is needed.

Adult↗
PubMed1999

Germline mutations of the LKB1 (STK11) gene in Peutz-Jeghers patients.

Germline mutations of the LKB1 (STK11) serine/threonine kinase gene (chromosome 19p13.3) cause Peutz-Jeghers syndrome, which is characterised by hamartomas of the gastrointestinal tract and typical pigmentation. Peutz-Jeghers syndrome carries an overall risk of cancer that may be up to 20 times that of the general population. Here, we report the results of a screen for germline LKB1 mutations by DNA sequencing in 12 Peutz-Jeghers patients (three sporadic and nine familial cases). Mutations were found in seven (58%) cases, in exons 1, 2, 4, 6, and 9. Five of these mutations, two of which are identical, are predicted to lead to a truncated protein (three frameshifts, two nonsense changes). A further mutation is an in frame deletion of 6 bp, resulting in a deletion of lysine and asparagine; the second of these amino acids is conserved between species. The seventh mutation is a missense change in exon 2, converting lysine to arginine, affecting non-conserved amino acids and of uncertain functional significance. Despite the fact that Peutz-Jeghers syndrome is usually an early onset disease with characteristic clinical features, predictive and diagnostic testing for LKB1 mutations will be useful for selected patients in both familial and non-familial contexts.

AMP-Activated Protein Kinase Kinases↗
PubMed1999

A novel putative low-affinity insulin-like growth factor-binding protein, LIBC (lost in inflammatory breast cancer), and RhoC GTPase correlate with the inflammatory breast cancer phenotype.

Inflammatory breast cancer is a rapidly growing, distinct form of locally advanced breast cancer that carries a guarded prognosis. To identify the genes that contribute to this aggressive phenotype, we compared under- and overexpressed sequences in an inflammatory breast tumor cell line with those of actively replicating normal human mammary epithelial cell lines using differential display. Of the 17 transcripts isolated and characterized from these experiments, overexpression of RhoC GTPase and loss of expression of a novel gene on 6q22, LIBC (lost in inflammatory breast cancer), were highly correlated (P<0.0095 and P<0.0013, respectively) with the inflammatory phenotype when a panel of archival inflammatory breast cancers was compared with noninflammatory stage III breast cancers by in situ hybridization. This study suggests two new molecular markers specific for inflammatory breast cancer.

Amino Acid Sequence↗
PubMed1999

Cognitive-behavioral group therapy versus phenelzine in social phobia: long-term outcome.

UNLABELLED: To evaluate the effects of maintenance treatment and durability of gains after treatment discontinuation, responders to either phenelzine (PZ) or cognitive-behavioral group therapy (CBGT) from an acute trial comparing these two treatments as well as pill placebo and a psychotherapy control (educational supportive group therapy) were enrolled into maintenance and treatment-free follow-up phases. EXPERIMENTAL DESIGN: Responders to an acute trial contrasting PZ and CBGT entered a six-month maintenance phase. Patients who continued to respond through the maintenance phase entered a six-month treatment free phase. Patients receiving pill placebo or educational supportive group therapy in the acute trial did not enter the long term study. PRINCIPAL OBSERVATIONS: PZ patients entered maintenance more improved than CBGT patients, and nonrelapsing PZ patients maintained their superior gains throughout the study. Relapse during maintenance did not differ between treatments. However, PZ patients showed a trend toward greater relapse during treatment-free follow-up. There was a greater relapse among patients with generalized social phobia with phenelzine. CONCLUSIONS: PZ and cognitive-behavioral group therapy may differ in their long term effects. The superiority seen with PZ on some measures in the acute study persisted in patients who maintained their gains over the course of maintenance and treatment-free follow-up. However, CBGT may lead to a greater likelihood of maintaining response after treatment has terminated. Replication with larger samples is needed, as is a study of the acute and long-term efficacy of combined PZ and CBGT.

Adult↗
PubMed1998

A christmas carol

Explore the source record for details and available documents.

Journal Article↗
PubMed1998

The synthesis of sub-micron magnetic particles and their use for preparative purification of proteins.

A novel one-step protocol for the preparation of sub-micron magnetic particles as small as 30 nm in diameter has been developed. The surface of the particles was functionalized with carboxyl groups ( approximately 1 COOH per 15A2) to facilitate the attachment of affinity ligands. The high surface area of the resulting beads, combined with the high density of functional groups on the surface, makes them ideally suited for the preparative purification of proteins as was demonstrated by the efficient isolation of trypsin (36 mg per gram of particles) from pancreatic extract.

Animals↗
PubMed1998

Enzymatic transformations in supersaturated substrate solutions: II. Synthesis of disaccharides via transglycosylation.

Enzymatic transglycosylation in supersaturated solutions of substrates was investigated using crude glycosidase preparations from barley, snail, and coffee beans. It was shown that the use of supersaturated glycoside solutions as media for transglycosylation reactions offers considerable advantages over conventional aqueous systems. These advantages include higher yields, more efficient use of the donor glycosides and improved volumetric productivity, especially in the case of poorly water-soluble substrates. The regioselectivity of the glycosylation was not significantly affected by high concentrations of acceptor glycosides. It was also shown that the regioselectivity of transfer could be directed towards secondary hydroxyl groups by the use of methyl 6-O-acetyl-alpha-galactopyranoside as acceptor. The value of these approaches was demonstrated by the synthesis of methyl 3- and 4-O-beta-D-galactopyranosyl-alpha-D-galactopyranosides and methyl 3-O-beta-D-galactopyranosyl-alpha-L-fucopyranoside on a preparative scale.

Carbohydrate Conformation↗
PubMed1998

The selective 5-HT1B receptor inverse agonist 1'-methyl-5-[[2'-methyl-4'-(5-methyl-1,2, 4-oxadiazol-3-yl)biphenyl-4-yl]carbonyl]-2,3,6,7-tetrahydro- spiro[furo[2,3-f]indole-3,4'-piperidine] (SB-224289) potently blocks terminal 5-HT autoreceptor function both in vitro and in vivo.

5-HT1 receptors are members of the G-protein-coupled receptor superfamily and are negatively linked to adenylyl cyclase activity. The human 5-HT1B and 5-HT1D receptors (previously known as 5-HT1Dbeta and 5-HT1Dalpha, respectively), although encoded by two distinct genes, are structurally very similar. Pharmacologically, these two receptors have been differentiated using nonselective chemical tools such as ketanserin and ritanserin, but the absence of truly selective agents has meant that the precise function of the 5-HT1B and 5-HT1D receptors has not been defined. In this paper we describe how, using computational chemistry models as a guide, the nonselective 5-HT1B/5-HT1D receptor antagonist 4 was structurally modified to produce the selective 5-HT1B receptor inverse agonist 5, 1'-methyl-5-[[2'-methyl-4'-(5-methyl-1,2, 4-oxadiazol-3-yl)biphenyl-4-yl]carbonyl]-2,3,6, 7-tetrahydrospiro[furo[2,3-f]indole-3,4'-piperidine] (SB-224289). This compound is a potent antagonist of terminal 5-HT autoreceptor function both in vitro and in vivo.

Animals↗
PubMed1998

Intravenous clomipramine for obsessive-compulsive disorder refractory to oral clomipramine: a placebo-controlled study.

BACKGROUND: Uncontrolled reports suggest that intravenous clomipramine hydrochloride may be effective for patients with obsessive-compulsive disorder (OCD) who are nonresponsive to oral clomipramine. METHODS: Fifty-four patients with oral clomipramine-refractory OCD were randomized to receive 14 infusions of either placebo or clomipramine hydrochloride, starting at 25 mg/d and increasing to 250 mg/d. Ratings were conducted double-blind after infusion 14 among 54 patients, single-blind 1 week later among 39 patients, and nonblind 1 month later among 31 patients. Response was based on a Clinical Global Impressions rating of at least "much improved." RESULTS: Six (21%) of 29 patients randomized to receive intravenous (i.v.) clomipramine vs 0 of 25 patients given i.v. placebo were responders after 14 infusions (df = 1, P<.02). Dimensional ratings after infusion 14 revealed significant (P = .007) improvement on the National Institute of Mental Health-Obsessive-Compulsive Scale and the Clinical Global Impressions Scale (P = .03), but not the Yale-Brown Obsessive Compulsive Scale. One week later, all dimensional measures of OCD showed significant improvement. At 1 week post-i.v., 9 (43%) of 21 patients initially randomized to i.v. clomipramine and treated subsequently with oral clomipramine were responders, whereas 0 of 18 patients initially randomized to receive i.v. placebo and treated subsequently with several days of open-label i.v. clomipramine responded (df = 1, P<.002). Of the 31 patients assessed 1 month after i.v. infusion (treatment not controlled), 18 (58.1%) were responders. Intravenous clomipramine treatment was safe with no serious adverse consequences. CONCLUSIONS: Intravenous clomipramine is more effective than i.v. placebo for patients with OCD with a history of inadequate response or intolerance to oral clomipramine. Further study of this promising treatment for refractory OCD is needed.

Administration, Oral↗