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Biomedical subjects

C Webb

Publications and source records attributed to C Webb.

At least 37 records · Page 2Linked to original sources
PubMed2000

Clinical research strategies in biotechnology.

Clinical drug development involves many steps and is extremely costly to the sponsoring company. There is intense pressure on sponsors to be faster, more efficient, and less costly. Sponsors also need to be globally oriented in their drug-development processes. There are several ways in which clinical drug development may be done more quickly and at less cost. These strategies include the use of large contract research organizations (CRO) and site management organizations (SMO). Although there is an estimated 2000 CRO worldwide, the use of SMO is quite limited but growing rapidly. Changes in the US Food and Drug Administration (FDA), especially harmonization between its two divisions Center for Biologics Evaluation and Research (CBER) and Center for Drug Evaluation and Research (CDER), and the use of CRO and SMO will make for interesting and challenging times for sponsors.

Biological Products↗
PubMed2000

Does the mechanism of action of biatrial pacing for atrial fibrillation involve changes in cardiac haemodynamics? Assessment by Doppler echocardiography and natriuretic peptide measurements.

AIMS: The antifibrillatory mechanism of biatrial (BI) pacing has not been fully elucidated. We investigated the role of a haemodynamic mechanism in eight patients implanted with a BI pacemaker (Chorus RM) by comparing changes in mitral Doppler flow and atrial and B-type natriuretic peptide levels (ANP, BNP) with BI pacing compared with sinus rhythm and right atrial (RA) pacing. METHODS AND RESULTS: Measurements were taken after 60 min in the supine position in each of two pairs of randomized pacing modes: (a) AAI40 beats x min(-1), (allows sinus rhythm mean rate 56 beats x min(-1), SR) vs AAI 40 beats x min(-1) with synchronized left atrial pacing (SRSync); (b) overdrive AAI RA pacing (89 beats x min(-1) (n = 6) or 70 beats x min(-1) (n = 2)) vs overdrive AAI BI pacing. Within each pair there was significant earlier activation of the left atrial Doppler signal in relation to the surface ECG P wave with BI pacing (SR 163 +/- 10 ms vs SRSync 144 +/- 21 ms (P = 0.02), and RA 232 +/- 14 ms vs BI 196 +/- 16 ms (P = 0.001)), and significant shortening of the P-R interval (SR 163 +/- 29 ms vs SRSync 148 +/- 20 (P = 0.007) and RA 261 +/- 27 ms vs BI 232 +/- 23 (P = 0.001)). The net observed effect was of no change in the atrioventricular timing sequence (delay of peak E or A to QRS/ mitral valve closure) and no change in other Doppler echo parameters. Levels of the cardiac peptides ANP and BNP were raised compared with healthy controls, but did not significantly change during the study. CONCLUSION: Acute BI pacing shortens the P-R interval and causes earlier left atrial contraction in relation to the surface electrocardiogram P wave. It does not alter the atrioventricular timing cycle, any other Doppler measurements or change cardiac peptide levels. This suggests that BI pacing does not cause haemodynamic changes that could account for any antifibrillatory properties.

Aged↗
PubMed2000

Improving door to needle times with nurse initiated thrombolysis.

OBJECTIVE: To evaluate the effect of nurse initiated thrombolysis on door to needle time (the interval between arriving at the hospital and starting thrombolytic treatment) in patients with acute myocardial infarction. DESIGN: Comparison of door to needle times before and after the employment of nurses trained and approved to initiate thrombolysis without prescription by a doctor but with a protocol for rapid triage of patients with chest pain. SETTING: A district general hospital. SUBJECTS: All patients admitted with suspected myocardial infarction between April 1995 and March 1999. MAIN OUTCOME MEASURES: Speed (door to needle time) and appropriateness of administration of thrombolytic drugs to patients with acute myocardial infarction who gave a characteristic history and had appropriate criteria on the admission ECG. RESULTS: During seven periods (each of four months) before the introduction of nurse initiated thrombolysis and a new chest pain triage protocol, the median door to needle time varied from 50-58 minutes. In four periods (each of 4-6 months) following the introduction of the changes, the median door to needle time was 25-30 minutes. The improvement was significant (p < 0.001). Nurses trained to initiate thrombolysis currently provide cover for 66% of the time. Median door to needle time for nurses was 15 minutes. Median door to needle time for junior doctors improved to 35 minutes. The median door to needle times when nurses initiated thrombolysis was significantly shorter than when doctors did so (p < 0.001). There have been no inappropriate management decisions by nurses approved to initiate thrombolysis. CONCLUSIONS: The use of nurse initiated thrombolysis has resulted in a clinically important reduction in the time taken for thrombolysis to be started in patients with acute myocardial infarction.

Coronary Care Units↗
PubMed2000

Regulation of sigma S degradation in Salmonella enterica var typhimurium: in vivo interactions between sigma S, the response regulator MviA(RssB) and ClpX.

The alternate sigma factor sigmaS plays an important role in the survival of Salmonella typhimurium following sudden encounters with a variety of stress conditions. The level of sigmaS is very low in rapidly growing cells but dramatically increases as those cells encounter environmental stress or enter into stationary phase. This increase is due in large measure to the stabilization of sigmaS protein against degradation by the ClpXP protease. The MviA protein, also known as RssB or SprE in Escherichia coli, is a putative member of a two component signal transduction system that plays a central role in facilitating sigmaS degradation by ClpXP. In contrast to most two-component systems, MviA does not appear to regulate gene expression but is believed to interact directly with sigmaS and somehow facilitate degradation. We now provide evidence that MviA(RssB) directly interacts both with sigmaS and ClpX in vivo, presumably enabling presentation of sigmaS to the ClpP protease. Interactions were demonstrated using a bacterial two-hybrid system in which sigmaS, MviA, and ClpX were fused to separate moieties of Bordetella pertussis CyaA (adenylate cyclase). Paired hybrid plasmids containing Cya'-MviA/RpoS-'Cya or Cya'-MviA/ClpX-'Cya successfully reconstituted adenylate cyclase activity in both S. typhimurium and E. coli. However, no direct interactions were detected between ClpX and RpoS. A second series of experiments has indicated that the interaction between MviA and sigmaS requires the N-terminus but not the C-terminus of MviA. Cellular levels of MviA appear to be very low in the cell based on lacZ fusion, Western blot and Northern blot analyses suggesting a catalytic role for MviA in sigmaS degradation. Mutagenesis of MviA residue D58, a canonical residue subject to phosphorylation in many two-component systems, decreased the ability of MviA to facilitate sigmaS turnover in vivo confirming that phosphorylation of MviA increases MviA activity.

ATPases Associated with Diverse Cellular Activitie↗
PubMed1999

Early and long-term results of a valve-sparing operation for Marfan syndrome.

BACKGROUND: We have previously described the experience, rationale, and development of a valve preserving technique, but its role in patients with Marfan syndrome has not previously been defined. Here, we attempt to determine the early and long-term results, timing, and determinants of outcome of this operation in patients with Marfan syndrome. METHODS AND RESULTS: Since 1979, 82 patients (73.2% of all patients with Marfan syndrome undergoing resection of aneurysm of the ascending aorta) were operated on using this technique. Ages ranged from 2 to 69 years (mean, 33.9 years). In all, there were 4 early deaths (4.9%), 2 with acute dissection and 2 with chronic aneurysm operated on as emergencies. There were no early deaths in 67 patients operated on electively. Actuarial survival for patients operated for chronic aneurysm was 94.2%, 94.2%, and 94.2% at 1, 5, and 10 years, respectively; that for acute dissection was 72.7%, 63. 6%, and 63.6%; and that for chronic dissection was 100%, 85.7%, and 75.0%. The probability of needing reoperation was 5.7%, 17.3%, and 17.3% at 1, 5, and 10 years. There were no instances of infective endocarditis or thromboembolic complications except in 2 patients operated on early in the series who had cusp extension. At the end of the follow-up, trivial or no aortic regurgitation was demonstrated in 33.3%, mild in 45.6%, moderate in 21.1%, and severe in 0. CONCLUSIONS: Valve-sparing operations are feasible in most patients with Marfan syndrome; they are applicable to patients with both dissection and chronic aneurysm. The early and long-term results are encouraging. Results are better in the absence of dissection, and prophylactic operation is warranted in some cases.

Adolescent↗
PubMed1999

Estrogen hits the surface.

Explore the source record for details and available documents.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1999

Analysing qualitative data: computerized and other approaches.

Analysis of qualitative data can be done 'manually' using a variety of techniques such as 'cut and paste' and use of coloured pens to categorize data and develop theoretical explanations. More recently a number of computer software packages have been developed to mechanize this 'coding' process as well as to search and retrieve data. This article reviews the background to and advantages and disadvantages of computerized approaches, and compares these with manual techniques used in a number of recent nursing PhD studies. It is concluded that beginning researchers conducting small-scale studies would be best recommended to use a manual approach in order to gain insight into the intuitive aspects of analysis which are the essential basis of any method of analysis, including computerized forms.

Anthropology, Cultural↗
PubMed1999

Pre-registration diploma students: a quantitative study of entry characteristics and course outcomes.

Nurse education has been transformed over the last decade and continuing change is likely. Nurse educators are responsible for meeting the quality assurance standards of local stakeholders and student retention and progress are important aspects of this process. As part of a monitoring exercise, an enquiry was set up to review pre-registration selection and recruitment strategies and to establish if there were any significant relationships between the characteristics of pre-registration diploma entrants and their academic achievement or completion rates. A multi-factorial tree-based technique was used for this purpose. This is one of the first British studies to consider both academic performance and completion rates for pre-registration diploma students. Four cohorts (N = 355) were studied. There was marked heterogeneity in student characteristics with a wide age distribution, a significant proportion of mature entrants with previous care experience, and considerable diversity in terms of education. Education and age were significant predictors of academic achievement: entrants with a minimum of two A levels and mature women with recent study experience did particularly well. Younger recruits with modest educational qualifications on entry performed less well in their assessments of theoretical knowledge. Younger students tended to leave more regularly, and well-qualified entrants showed a greater tendency to complete, although these relationships were not statistically significant. Multi-factorial analysis demonstrated that organisational and course characteristics have a conjoint influence on course outcomes. Although the study is concerned with Project 2000 in the United Kingdom, there are lessons to be drawn concerning the selection and support of non-traditional recruits into nursing.

Achievement↗
PubMed1999

Effects of DksA and ClpP protease on sigma S production and virulence in Salmonella typhimurium.

Salmonella typhimurium responds to a variety of environmental stresses by accumulating the alternative sigma factor sigmaS. The repertoire of sigmaS -dependent genes that are subsequently expressed confers tolerance to a variety of potentially lethal conditions including low pH and stationary phase. The mechanism(s) responsible for triggering sigmaS accumulation are of considerable interest, because they help to ensure survival of the organism during encounters with suboptimal environments. Two genes associated with regulating sigmaS levels in S. typhimurium have been identified. The first is clpP, encoding the protease known to be responsible for degrading sigmaS in Escherichia coli. The second is dksA, encoding a protein of unknown function not previously associated with regulating sigmaS levels. As predicted, clpP mutants accumulated large amounts of sigmaS even in log phase. However, dksA mutants failed to accumulate sigmaS in stationary phase and exhibited lower accumulation during acid shock in log phase. DksA appears to be required for the optimal translation of rpoS based upon dksA mutant effects on rpoS transcriptional and translational lacZ fusions. The region of rpoS mRNA between codons 8 and 73 is required to see the effects of dksA mutations. This distinguishes the role of DksA from that of HF-I (hfq ) in rpoS translation, as the HF-I target area occurs well upstream of the rpoS start codon. DksA appears to be involved in the expression of several genes in addition to rpoS based on two-dimensional SDS-PAGE analysis of whole-cell proteins. As a result of their effects on gene expression, mutations in clpP and dksA decreased the virulence of S. typhimurium in mice, consistent with a role for sigmaS in pathogenesis.

Adenosine Triphosphatases↗
PubMed1998

Burden and well-being of caregivers for the severely mentally ill: the role of coping style and social support.

Caregivers of persons with severe mental illness often experience a significant burden in coping with patients' symptoms. Several factors have been hypothesized to mediate the impact of caring for a mentally ill relative, including cognitive appraisal, coping strategies, and social support. The present study examined the relationships between these factors, and subjective burden and well-being in caregivers of persons with a severe mental illness. Higher levels of subjective burden were related to (1) greater perceived frequency of positive and negative symptom behaviors, (2) a tendency to use problem-focused oriented coping for dealing with negative symptom behaviors, and (3) a tendency not to use problem-solving oriented coping for dealing with positive symptom behaviors. Well-being was also related to lower perceived frequency of positive symptom behaviors and social support, but not to coping style. The implications of the findings for interventions designed to reduce caregiver subjective burden are discussed.

Adaptation, Psychological↗
PubMed1998

PD 176252--the first high affinity non-peptide gastrin-releasing peptide (BB2) receptor antagonist.

In this paper we describe the development of a novel series of non-peptide, "balanced" neuromedin-B preferring (BB1)/gastrin-releasing peptide preferring (BB2) receptor ligands as exemplified by PD 176252. PD 176252, which exhibits nanomolar affinity for both the BB1 (Ki = 0.15 nM) and BB2 (Ki = 1.0 nM) receptors, has been demonstrated to be a competitive antagonist at these bombesin receptor subtypes.

Animals↗
PubMed1998

Stimulatory effect of 660 nm low level laser energy on hypertrophic scar-derived fibroblasts: possible mechanisms for increase in cell counts.

BACKGROUND AND OBJECTIVE: Varying effects of red light wavelengths on in vitro cells have been reported. Low level lasers (LLL) are employed to assist wound healing especially for indolent ulcers. On healing, burn wounds may become hypertrophic, resulting in excessive wound contraction, poor cosmesis, and functional impairment. This study enquired whether 660 nm LLL affected hypertrophic scar-derived fibroblasts. STUDY DESIGN/MATERIALS AND METHODS: The experiments investigated the effect of a 660 nm, 17 mW laser diode at dosages of 2.4 J/cm2 and 4 J/cm2 on cell counts of two human fibroblast cell lines, derived from hypertrophic scar tissue (HSF) and normal dermal (NDF) tissue explants, respectively. The protocol avoided transfer of postirradiated cells. Estimation of fibroblasts utilized the methylene blue bioassay. RESULTS/CONCLUSION: The post-660 nm-irradiated HSFs exhibited very significantly higher cell counts than controls P < 0.01 on days 1-4 (Mann-Whitney U-test), and P < 0.01 on days 1-3 for similarly irradiated NDFs.

Adult↗
PubMed1998

Design and implementation of the Dual Site Atrial Pacing to Prevent Atrial Fibrillation (DAPPAF) clinical trial. DAPPAF Phase 1 Investigators.

The Dual Site Atrial Pacing to Prevent Atrial Fibrillation (DAPPAF) study compares dual site, single site and support pacing modalities in the prevention of atrial fibrillation (AF) in patients with a history of paroxysmal AF (PAF) and a bradyarrhythmic indication for pacing. The trial is a randomized crossover comparison of dual site atrial pacing, single site atrial pacing, and a support pacing control period (DDI at 50 ppm or VDI) done in six month intervals. Patient inclusion requires at least 2 documented AF episodes in the three months prior to enrollment. The patients can be on concurrent antiarrhythmic drug regimens but this regimen must remain constant throughout the protocol. Patients with AV nodal ablation are excluded from this study. The primary endpoints of the study compare the time to first recurrence of clinically significant symptomatic AF with ECG verification, and quality of life among the three treatment modes. Secondary endpoints include time to first recurrence of all AF episodes as monitored by the pacemaker, the measurement of echocardiographic parameters, and symptoms logged by the patients. This trial was designed after pilot studies showed dual site pacing to be safe, feasible and preliminary results suggested increased maintenance of sinus rhythm with atrial pacing.

Adult↗
PubMed1998

Consensus guidelines for the promotion and management of continence by primary health care teams: development, implementation and evaluation. NHS Executive Nursing Directorate.

A project was undertaken as part of the NHS Executive Strategy for Major Clinical Guidelines, involving the development of national clinical guidelines for the promotion and management of continence by primary health care teams, through the process of managed consensus based on scientific review. The guidelines were then implemented at one urban general practice. This article outlines the development and implementation of the guidelines and describes the study undertaken to evaluate the impact of implementation on clinical outcomes. The study involved a pre-and post-implementation postal survey of a random sample of 17% of patients aged 18 years and over from the practice (n = 1503). The pre-implementation survey determined the period prevalence of incontinence, related biological data and data on the pre-implementation management of incontinence. Incontinence sufferers were invited to have their condition assessed or reviewed. All sufferers who agreed to be followed-up were sent the post-implementation survey, which identified those patients who had sought help, and ascertained reasons for not seeking help. Data on the management of incontinence post-implementation were also obtained. Clinical outcomes measured pre- and post-implementation were a validated severity index for urinary incontinence, (also adapted for faecal incontinence) and perception of the incontinence as a problem. A 3-month period was allowed between pre- and post-implementation surveys. The study confirmed previous research which showed that few incontinence sufferers respond to invitations to seek help, and that help-seeking behaviour was significantly related to severity of incontinence. The guidelines did not have any positive impact on the clinical outcomes measured, although slight improvements in approaches taken by the primary health care team to the promotion and management of continence were recorded. However, the study was limited by the small sample size and short time scale. Further evaluation of the impact of the guidelines on these outcomes is therefore recommended.

Female↗