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Biomedical subjects

S Walker

Publications and source records attributed to S Walker.

At least 55 records · Page 3Linked to original sources

Randomized controlled study investigating the effect of biatrial pacing in prevention of atrial fibrillation after coronary artery bypass grafting.

BACKGROUND: Atrial fibrillation (AF) is a common problem after CABG. Prevention with prophylactic drug therapy has had limited success, therefore alternative approaches are required. This study investigated the role of biatrial pacing compared with no pacing on AF incidence after isolated first-time CABG. METHODS AND RESULTS: During surgery, temporary pacing leads were placed in the lateral wall of the right atrium and at the roof of the left atrium in Bachmann's bundle to allow bipolar pacing and sensing at each site. After surgery, all patients were connected to an external pacemaker (Chorum ELA) that also acted as a Holter monitor. Patients were consecutively randomized to either 4 days of biatrial pacing at a base rate of 80 bpm or to no pacing (control group, base rate 30 bpm). End points included an episode of AF lasting >1 hour on pacemaker Holter, clinically detected AF, intensive care unit (ICU) and hospital stay, and postoperative complications. One hundred thirty patients were randomized. Biatrial pacing significantly reduced both monitored (13.8% versus 38.5%, P:=0.001) and clinical (10.8% versus 33.8%, P:=0.002) episodes of AF. Median ICU (19 versus 24 hours, P:=NS) and mean hospital stay (7.7+/-6.9 versus 9.7+/-10, P:=NS) did not significantly change. The number of postoperative complications was lower in the biatrial group (13 versus 35, P:=0. 001). CONCLUSIONS: Biatrial pacing after CABG significantly decreases the incidence of AF. This is associated with reduced postoperative complications and a trend toward reduced ICU and hospital stay.

Aged↗

Ablate and pace for drug refractory paroxysmal atrial fibrillation. Is ablation necessary?

BACKGROUND: Atrio-ventricular junctional ablation with pacemaker insertion has been shown to improve quality of life in patients with drug refractory paroxysmal atrial fibrillation. It is unknown whether this improvement is secondary to the ablation procedure or to the pacemaker mode utilised. To investigate this we reviewed our experience of implanting a dual chamber rate responsive pacemaker with mode switching (DDDR/MS) alone on quality of life in this patient group. METHODS AND RESULTS: Over a 1-year period, 19 patients (mean age 62+/-9 years, 13 female) with drug refractory paroxysmal atrial fibrillation (mean duration of symptoms 8.7+/-7 years, failed 3.1+/-0.9 anti-arrhythmic drugs, amiodarone in 15) were recruited. Quality of life was assessed at baseline and after 1 month using a cardiac specific questionnaire, the modified Karolinska questionnaire. The mean score for all patients significantly improved by 39% at follow up (baseline 59+/-24, 1 month 36+/-24, P=0.001). Individually 15 patients (79%) had an improvement in their score, whilst for 13 patients (68%) their symptoms were sufficiently improved after pacing that ablation was not required. The benefit was maintained to a mean follow up of 12+/-5 months (score 31+/-20, P<0.001). Six patients remained symptomatic after pacing and requested further treatment. Benefit was unrelated to symptoms at baseline or the number and total duration of paroxysmal atrial fibrillation episodes recorded on pacemaker Holter. CONCLUSIONS: Patients with drug refractory paroxysmal atrial fibrillation, DDDR/MS pacing alone can improve quality of life without concurrent atrio-ventricular junctional ablation in a significant proportion of patients.

Aged↗

The early experience of general practitioners using Green Prescription.

AIM: Sedentary lifestyle is a significant risk factor for increased morbidity and mortality in many medical conditions. A Hillary Commission initiative, Green Prescription is a written exercise prescription given by general practitioners (GPs) to sedentary patients to encourage physical activity. Our aim was to establish the extent to which GPs in the North Health region in 1997 issued with Green Prescription packages had used them, the circumstances under which they were used, and barriers to their use. METHODS: 433 GPs issued with packs were faxed a one-page questionnaire for immediate completion, with follow-up of non-responders. RESULTS: The response rate was 73%, with 65% of respondents having written Green Prescriptions. Their main reasons for use were patient need for more exercise and presence of high-risk medical conditions such as hypertension, cardiovascular disease, obesity and diabetes. Reasons for non-use were: GP already giving advice about physical activity; concern that Green Prescription was patronising and simplistic; compliance issues and time restraints. Some requested a computerised version. CONCLUSION: Non-responders may be non-users, hence we estimate that 48-65% of targeted GPs used Green Prescription. Barriers identified by GPs have assisted in Green Prescription development, which is now nationwide and assessed by independent researchers tri-annually.

Adult↗

Cloned pigs produced by nuclear transfer from adult somatic cells.

Since the first report of live mammals produced by nuclear transfer from a cultured differentiated cell population in 1995 (ref. 1), successful development has been obtained in sheep, cattle, mice and goats using a variety of somatic cell types as nuclear donors. The methodology used for embryo reconstruction in each of these species is essentially similar: diploid donor nuclei have been transplanted into enucleated MII oocytes that are activated on, or after transfer. In sheep and goat pre-activated oocytes have also proved successful as cytoplast recipients. The reconstructed embryos are then cultured and selected embryos transferred to surrogate recipients for development to term. In pigs, nuclear transfer has been significantly less successful; a single piglet was reported after transfer of a blastomere nucleus from a four-cell embryo to an enucleated oocyte; however, no live offspring were obtained in studies using somatic cells such as diploid or mitotic fetal fibroblasts as nuclear donors. The development of embryos reconstructed by nuclear transfer is dependent upon a range of factors. Here we investigate some of these factors and report the successful production of cloned piglets from a cultured adult somatic cell population using a new nuclear transfer procedure.

Animals↗

Why are antibiotics prescribed for asymptomatic bacteriuria in institutionalized elderly people? A qualitative study of physicians' and nurses' perceptions.

BACKGROUND: Antibiotic therapy for asymptomatic bacteriuria in institutionalized elderly people has not been shown to be of benefit and may in fact be harmful; however, antibiotics are still frequently used to treat asymptomatic bacteriuria in this population. The aim of this study was to explore the perceptions, attitudes and opinions of physicians and nurses involved in the process of prescribing antibiotics for asymptomatic bacteriuria in institutionalized elderly people. METHODS: Focus groups were conducted among physicians and nurses who provide care to residents of long-term care facilities in Hamilton, Ont. A total of 22 physicians and 16 nurses participated. The focus group discussions were tape-recorded, and the transcripts of each session were analysed for issues and themes emerging from the text. Content analysis using an open analytic approach was used to explore and understand the experience of the focus group participants. The data from the text were then coded according to the relevant and emergent themes and issues. RESULTS: We observed that the ordering of urine cultures and the prescribing of antibiotics for residents with asymptomatic bacteriuria were influenced by a wide range of nonspecific symptoms or signs in residents. The physicians felt that the presence of these signs justified a decision to order antibiotics. Nurses played a central role in both the ordering of urine cultures and the decision to prescribe antibiotics through their awareness of changes in residents' status and communication of this to physicians. Education about asymptomatic bacteriuria was viewed as an important priority for both physicians and nurses. INTERPRETATION: The presence of non-urinary symptoms and signs is an important factor in the prescription of antibiotics for asymptomatic bacteriuria in institutionalized elderly people. However, no evidence exists to support this reason for antibiotic treatment. Health care providers at long-term care facilities need more education about antibiotic use and asymptomatic bacteriuria.

Aged↗

CREB contributes to the increased neurite outgrowth of sensory neurons induced by vasoactive intestinal polypeptide and activity-dependent neurotrophic factor.

Our recent experiments suggest that vasoactive intestinal polypeptide (VIP) enhances neurite outgrowth of dissociated rat dorsal root ganglion cells, indirectly, via the release of a trophic factor from the spinal cord. In this study, we have examined the possible contribution of activity-dependent neurotrophic factor (ADNF) to the trophic actions of VIP. In addition, as we have shown that the factor mediating the trophic actions of VIP acts via protein kinase A we have also examined the contribution of CREB, which is a transcription factor activated by protein kinase A. As previously shown, supernatant taken from spinal cord incubated with VIP, significantly increased the percentage of sensory neurons with neurites. Antiserum against ADNF attenuated the trophic effect of the VIP-conditioned supernatant. Consistently, the ADNF agonist, ADNF(14) (0.001-0.1 fM), significantly enhanced the percentage of cells with neurite outgrowth. Furthermore, the trophic action of ADNF(14) was attenuated by a protein kinase A inhibitor, Rp-cAMPS, whereas the inactive isomer, Sp-cAMPS, had no effect. Preincubation of cells with 5 mcM CREB antisense oligonucleotides, attenuated the increase in neurite outgrowth induced by either the supernatant or ADNF(14). The sense oligonucleotide had no influence on the enhanced neurite outgrowth. We also found that both the supernatant and ADNF(14) induced an increase in the percentage of cells expressing phosphorylated CREB. The data suggests that VIP induces a release of neurotrophic factors, such as ADNF, which enhance neurite outgrowth. In addition, protein kinase A and CREB appear to contribute to the neurotrophic actions of VIP and ADNF. The mechanisms underlying the neurotrophic action of VIP, may have important implications for sprouting and/or synaptic reorganization of central terminals of sensory neurons, which may contribute to neuropathic pain that commonly occurs following peripheral nerve damage.

Animals↗

Photon-mediated hybridization of frenkel excitons in organic semiconductor microcavities

Coherent excitations of intricate assemblies of molecules play an important role in natural photosynthesis. Microcavities are wavelength-dimension artificial structures in which excitations can be made to couple through their mutual interactions with confined photon modes. Results for microcavities containing two spatially separated cyanine dyes are presented here, where simultaneous strong coupling of the excitations of the individual dyes to a single cavity mode leads to new eigenmodes, described as admixtures of all three states. These "hybrid" exciton-photon structures are of potential interest as model systems in which to study energy capture, storage, and transfer among coherently coupled molecular excitations.

Journal Article↗

Effect of changes in expression of the amphotropic retroviral receptor PiT-2 on transduction efficiency and viral titer: implications for gene therapy.

The aim of this study was to quantify the impact of amphotropic retroviral receptor (PiT-2) levels on susceptibility to transduction and to determine whether the low level of PiT-2 found on CD34+ hematopoietic cells is within the range likely to compromise gene transfer. Receptor-deficient Chinese hamster ovary (CHO) cells were transfected with a PiT-2 construct that could be induced by the removal of tetracycline. The level of PiT-2 expression measured by virus binding in uninduced and in fully and partially induced transfectants correlated with the efficiency of transduction by an amphotropic retroviral reporter vector. Fully induced CHO-PiT-2 cells gave apparent viral titers similar to NIH 3T3 fibroblasts while addition of tetracycline reduced titers by up to 140-fold. Binding of the same vector preparation to purified CD34+ peripheral blood stem cells (PBSCs) was always less than to uninduced CHO-PiT-2 transfectants even after preincubation in 10-ng/ml concentrations of IL-3, IL-6, and stem cell factor, which increased retroviral binding by an average of 35%. The level of expression of the amphotropic retroviral receptor PiT-2 thus significantly limits transduction efficiency within the range observed in target cells of importance in human gene therapy.

3T3 Cells↗

The prognostic significance of abnormalities seen on magnetic resonance imaging in late life depression: clinical outcome, mortality and progression to dementia at three years.

OBJECTIVE: To study the course of depressive symptoms over 3 years, rate of dementia and mortality in relation to baseline neuroradiological abnormalities. DESIGN: Retrospective casenote analysis of 38 patients (of 44) who had a Magnetic Resonance Imaging (MRI) scan 3 years earlier. Twenty-two patients also received a detailed interview. RESULTS: Overall outcome was good for around two-thirds of the sample. Poorer clinical course was associated with lesions in pons and more than five Virchow Robins spaces in the corona radiata. Pontine raphe lesions and confluent periventricular lesions were associated with later dementia and with reduced survival from cardiovascular death. Males had more recurrences and a reduced survival. CONCLUSIONS: MRI lesions influence outcome, mortality and the onset of dementia. However, because they are quite common in elderly depressed patients they have limited utility on their own as predictors of outcome. The association of periventricular lesions with dementia is a new finding, and suggests that the site and type of lesions may be as important than the quality of them.

Aged↗

The value of limited computed tomography with rectal contrast in the diagnosis of acute appendicitis.

BACKGROUND: Multiple nonrandomized studies demonstrate the accuracy of computed tomography (CT) scan in diagnosing appendicitis. This study compared CT scan with standard management in diagnosing appendicitis. METHODS: This was a prospective randomized study of patients who received general surgery consultation for appendicitis. Patients were randomized to receive CT scan or standard management. RESULTS: There were 65 patients in the CT scan group and 63 patients in the standard management group. The sensitivity, specificity, and accuracy of CT scan were 94%, 100%, and 96%, respectively. CT scan positively altered the management in 26% and made alternative diagnoses in 14%. The sensitivity, specificity, and accuracy of the standard management group were 100%, 79%, and 89%, respectively. The standard management group had a negative appendectomy rate of 19%. CONCLUSION: CT scan with rectal contrast is an effective method for diagnosing appendicitis and should be performed in all patients suspected of having appendicitis.

Acute Disease↗

Does atrial overdrive pacing prevent paroxysmal atrial fibrillation in paced patients?

The role of atrial overdrive pacing for the suppression of paroxysmal atrial fibrillation remains unclear. To investigate this we have performed a randomised study evaluating the role of an increased atrial base rate in suppressing this arrhythmia in patients implanted with a permanent pacemaker (Chorum ELA) for sick sinus syndrome with previous documented paroxysmal atrial fibrillation. Twenty-seven patients (mean age, 69; 15 female) were randomised to two 3-month single-blinded crossover periods of DDDR pacing. The pacemaker was set with a base rate of 60 bpm (normal) during one period and at 10 bpm (overdrive) above the average heart rate during the other, mean (S.D.) 75+/-7 beats/min (range, 70-96). The fallback algorithm of the pacemaker was activated to record the number and duration of paroxysmal atrial fibrillation episodes. During the overdrive period there was a significant increase in the total duration of atrial pacing (normal 60+/-26% vs. overdrive 72+/-28%, P<0.001). However there was no significant difference in the number of paroxysmal atrial fibrillation episodes (normal 43+/-109 vs. overdrive 43+/-106, P=ns), or their total duration (normal 42+/-108 h vs. overdrive 99+/-254 h, P=ns). In conclusion, atrial overdrive pacing, achieved by increasing the atrial base rate, has no incremental benefit in the suppression of paroxysmal atrial fibrillation when compared to rate responsive pacing with a base rate of 60 bpm.

Aged↗

The impact of epilepsy from the patient's perspective I. Descriptions and subjective perceptions.

This study surveyed the perceptions about and subjective experience of 1023 people with epilepsy in two community-based samples: one from a national postal survey; the other callers to the Epilepsy Foundation. Response to a mail survey was 49%. In comparison with US Census Bureau norms, respondents had received less education, were less likely to be employed or married, and came from lower income households. Complex partial seizures were the most prevalent seizure type, but a convulsion had occurred in 61%. Fifty percent of respondents reported incomplete control of their seizure disorder, although 25% of these had a seizure in the prior year. Thirteen percent had a longest inter-seizure interval of a year or greater, 37% of 3 months, 22% of 1 month, 10% of 1 week and 4% of 1 day. Respondents listed uncertainty and fear of having a seizure as the worst thing about having epilepsy. Lifestyle, school, driving, and employment limits were also listed as major problems. When asked to rank a list of potential problems, cognitive impairment was ranked highest. These data indicate that ongoing medical and psychosocial problems continue for those with epilepsy in the view of those questioned and their families, even in a sample where the majority report good control of their epilepsy.

Adolescent↗

A potential RNA drug target in the hepatitis C virus internal ribosomal entry site.

Subdomain IlId from the hepatitis C virus (HCV) internal ribosome entry site (IRES) has been shown to be essential for cap-independent translation. We have conducted a structural study of a 27-nt fragment, identical in sequence to IlId, to explore the structural features of this subdomain. The proposed secondary structure of IlId is comprised of two 3 bp helical regions separated by an internal loop and closed at one end by a 6-nt terminal loop. NMR and molecular modeling were used interactively to formulate a validated model of the three-dimensional structure of IlId. We found that this fragment contains several noncanonical structural motifs and non-Watson-Crick base pairs, some of which are common to other RNAs. In particular, a motif characteristic of the rRNA alpha-sarcin/ricin loop was located in the internal loop. The terminal loop, 5'-UUGGGU, was found to fold to form a trinucleotide loop closed by a trans-wobble U.G base pair. The sixth nucleotide was bulged out to allow stacking of this U.G pair on the adjacent helical region. In vivo mutational analysis in the context of the full IRES confirmed the importance of each structural motif within IIId for IRES function. These findings may provide clues as to host cellular proteins that play a role in IRES-directed translation and, in particular, the mechanism through which host ribosomes are sequestered for viral function.

Base Pairing↗

Underreporting of energy intake in four populations of African origin.

OBJECTIVE: To investigate the frequency of dietary underreporting in four African populations in different geographic and cultural settings. SUBJECTS: Seven-hundred and forty three men and women from rural Cameroon, 1042 men and women from urban Cameroon, 857 men and women from Jamaica and 243 male and female African Caribbeans from the UK. Subjects who reported dieting or weight control were excluded. MEASUREMENTS: Habitual dietary intake was estimated with a quantitative food frequency questionnaire, developed specifically for each country. Underreporting was defined using three cut-off levels for energy intake/estimated basic metabolic rate (EI/BMRest), based on age, sex and weight, in each site. RESULTS: The EI/BMRest was highest in rural Cameroonian men at 3.07 (95% confidence interval: 2.97, 3.17) and women at 2.84 (2.74, 2.94), intermediate in urban Cameroon and Jamaica and lowest in the UK men and women at 1.44 (1.26, 1.62) and 1.41 (1.21, 1.61). This trend existed even after adjustment for age, BMI and education (P for trend<0.0001). The trend in the frequency of underreporting using the lowest cut-off level for EI/BMRest of 1.15 was 6% and 6% in rural Cameroon for women and men, respectively, 4% and 5% in urban Cameroon, 24% and 19% in Jamaica and 28% and 39% in the UK. With higher cut off levels this trend was similar. CONCLUSION: The results suggest that the frequency of dietary underreporting differs between societies and that Westernization may be one of the factors underlying this phenomenon.

Adult↗

Feasibility of using dynamic contrast-enhanced magnetic resonance angiography as the sole imaging modality prior to endovascular repair of abdominal aortic aneurysms.

OBJECTIVES: to establish the feasibility of using magnetic resonance imaging (MRI) with dynamic contrast-enhanced (DCE) MRA as the sole imaging modality in the assessment of patients prior to endovascular repair of abdominal aortic aneurysms (AAAs). DESIGN: DCE MRA with MRI and helical computed tomography (CT) examinations were performed in patients being assessed for suitability for an endovascular approach to repair of their AAA. Management outcomes determined by the two techniques were compared. MATERIALS: sixteen patients with AAA. METHODS: all subjects underwent DCE MRA/MRI and helical CTA. Criteria for suitability for endovascular repair were established. The management outcomes determined by the MRI findings were compared with those obtained by CTA. RESULTS: high-quality MRA/MRI and CT images were obtained in 16 patients. Six patients were considered suitable for an endovascular approach, one was considered borderline and nine were judged unsuitable. In all cases, the overall management determined by the two methods concurred. CONCLUSIONS: comparison of the two imaging modalities resulted in agreement as to suitability for an endovascular approach. We therefore conclude that in our group the use of MRI and DCE-MRA proved effective as a sole imaging modality for the assessment of these patients.

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