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J Webster

Publications and source records attributed to J Webster.

At least 37 records · Page 2Linked to original sources

Course, management and outcome of oral-anticoagulant-related intracranial haemorrhages.

The aim of this study was to compare the clinical course and radiological features of oral anticoagulant (OAC)-related intracranial haemorrhages with those of haemorrhages unrelated to OAC use admitted over the last six years to a tertiary care centre in the North of Scotland. We furthermore wished to determine the measures taken for reversal of OAC therapy and the resulting short-term outcome. Sixty-eight patients had been treated with OACs at the time of intracranial haemorrhage (32% subdural, 62% intracerebral). Patients admitted with OAC-related and unrelated haemorrhages did not differ significantly in any of the clinical features considered. On CT scan, there was no significant difference according to OAC use in the mean size of subdural (depth 15 +/- 5 vs. 18 +/- 8 mm, p = 0.36), or intracerebral haematomas (max. diameter 40 +/- 21 vs. 41 +/- 20 mm, p = 0.73). No reversal measures were taken in 38% of OAC-treated patients. In-hospital mortality was significantly higher for OAC-related haemorrhages compared to unrelated haemorrhages (38% vs. 18%, p = 0.001). To further elucidate the effects of anticoagulant reversal on the outcome of OAC-related intracranial haemorrhages, a large-scale prospective study is warranted.

Anticoagulants↗

A comparison of two approaches in the treatment of perceptual problems after stroke.

OBJECTIVE: To compare the effectiveness of the transfer of training and functional approaches in improving perceptual and functional abilities after stroke. DESIGN: Patients identified as having perceptual problems were randomly allocated to either the transfer of training approach or the functional approach for perceptual treatment. On completion of six weeks of treatment, each patient was reassessed for perceptual and functional abilities. SUBJECTS AND SETTING: Eighty inpatients on the Nottingham Stroke Unit. INTERVENTIONS: Perceptual treatment was given for 2.5 hours per week for six weeks. MAIN OUTCOME MEASURES: Rivermead Perceptual Assessment Battery, Barthel ADL Index and Edmans ADL index. RESULTS: There was no significant difference between the treatment groups on patient characteristics or impairments. The results also showed no significant difference between the treatment groups before and after treatment on perceptual ability total scores, individual perceptual subtest scores, or functional ability total scores (Mann-Whitney U 642.5-798.0, p > 0.05). Wilcoxon matched pairs signed ranks tests showed a significant improvement in both groups after treatment on perceptual and functional abilities (perceptual z = 6.02, p < 0.001, functional z = 6.72, p < 0.001). CONCLUSIONS: These results indicated that the improvement in perceptual abilities was equivalent using either of the two approaches. This could be due to spontaneous recovery or the effects of the Stroke Unit.

Activities of Daily Living↗

Predicting cardiovascular risk using conventional vs ambulatory blood pressure in older patients with systolic hypertension. Systolic Hypertension in Europe Trial Investigators.

CONTEXT: The clinical use of ambulatory blood pressure (BP) monitoring requires further validation in prospective outcome studies. OBJECTIVE: To compare the prognostic significance of conventional and ambulatory BP measurement in older patients with isolated systolic hypertension. DESIGN: Substudy to the double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) Trial, started in October 1988 with follow up to February 1999. The conventional BP at randomization was the mean of 6 readings (2 measurements in the sitting position at 3 visits 1 month apart). The baseline ambulatory BP was recorded with a noninvasive intermittent technique. SETTING: Family practices and outpatient clinics at primary and secondary referral hospitals. PARTICIPANTS: A total of 808 older (aged > or =60 years) patients whose untreated BP level on conventional measurement at baseline was 160 to 219 mm Hg systolic and less than 95 mm Hg diastolic. INTERVENTIONS: For the overall study, patients were randomized to nitrendipine (n = 415; 10-40 mg/d) with the possible addition of enalapril (5-20 mg/d) and/or hydrochlorothiazide (12.5-25.0 mg/d) or to matching placebos (n = 393). MAIN OUTCOME MEASURES: Total and cardiovascular mortality, all cardiovascular end points, fatal and nonfatal stroke, and fatal and nonfatal cardiac end points. RESULTS: After adjusting for sex, age, previous cardiovascular complications, smoking, and residence in western Europe, a 10-mm Hg higher conventional systolic BP at randomization was not associated with a worse prognosis, whereas in the placebo group, a 10-mm Hg higher 24-hour BP was associated with an increased relative hazard rate (HR) of most outcome measures (eg, HR, 1.23 [95% confidence interval [CI], 1.00-1.50] for total mortality and 1.34 [95% CI, 1.03-1.75] for cardiovascular mortality). In the placebo group, the nighttime systolic BP (12 AM-6 AM) more accurately predicted end points than the daytime level. Cardiovascular risk increased with a higher night-to-day ratio of systolic BP independent of the 24-hour BP (10% increase in night-to-day ratio; HR for all cardiovascular end points, 1.41; 95% CI, 1.03-1.94). At randomization, the cardiovascular risk conferred by a conventional systolic BP of 160 mm Hg was similar to that associated with a 24-hour daytime or nighttime systolic BP of 142 mm Hg (95% CI, 128-156 mm Hg), 145 mm Hg (95% CI, 126-164 mm Hg) or 132 mm Hg (95% CI, 120-145 mm Hg), respectively. In the active treatment group, systolic BP at randomization did not significantly predict cardiovascular risk, regardless of the technique of BP measurement. CONCLUSIONS: In untreated older patients with isolated systolic hypertension, ambulatory systolic BP was a significant predictor of cardiovascular risk over and above conventional BP.

Aged↗

Studies with a growth hormone antagonist and dual-fluorescent confocal microscopy demonstrate that the full-length human growth hormone receptor, but not the truncated isoform, is very rapidly internalized independent of Jak2-Stat5 signaling.

UNLABELLED: We have investigated trafficking of two negative regulators of growth hormone receptor (GHR) signaling: a human, truncated receptor, GHR1-279, and a GH antagonist, B2036. Fluorescent-labeled growth hormone (GH) was rapidly internalized by the full-length GHR, with >80% of the hormone internalized within 5 min of exposure to GH. In contrast, <5% of labeled GH was internalized by cells expressing truncated GHR1-279. Using another truncated receptor, GHR1-317 fused to enhanced green fluorescent protein (EGFP), we have exploited fluorescence energy transfer to monitor the trafficking of ligand-receptor complexes. The data confirmed that internalization of this truncated receptor is very inefficient. It was possible to visualize the truncated GHR1-317-EGFP packaged in the endoplasmic reticulum, its rapid movement in membrane bound vesicles to the Golgi apparatus, and subsequent transport to the cell membrane. The GH antagonist, B2036, blocked Jak2-Stat5-mediated GHR signaling but was internalized with a similar time course to native GH. THE RESULTS: 1) demonstrate the rapid internalization of GH when studied under physiological conditions; 2) confirm the hypothesis that internalization of cytoplasmic domain truncated human GHRs is very inefficient, which explains their dominant negative action; and 3) show that the antagonist action of B2036 is independent of receptor internalization.

Golgi Apparatus↗

Development of evidence-based guidelines in midwifery and gynaecology nursing.

OBJECTIVE: To develop an effective and efficient method for basing nursing practice on research evidence. SETTING: The Royal Women's Hospital, Brisbane, Australia. METHOD: Nurses and midwives from various clinical areas were invited to participate in an evidence-based practice project. Standard procedures for retrieving relevant articles and evaluating their quality were observed. Where possible, raw data from studies with similar methods were summarised using appropriate statistical tests. FINDINGS: Several guidelines have been developed, staff involved with the project have become 'research literate' and the project is contributing to the hospital-wide quality improvement activities. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: It is possible to translate research findings into practice when small groups use systematic reviews to develop practice guidelines.

Australia↗

Systolic Hypertension in Europe (Syst-Eur) trial phase 2: objectives, protocol, and initial progress. Systolic Hypertension in Europe Investigators.

The Systolic Hypertension in Europe (Syst-Eur) trial proved that blood pressure (BP) lowering therapy starting with nitrendipine reduces the risk of cardiovascular complications in older (> or = 60 years) patients with isolated systolic hypertension (systolic BP > or = 160 mm Hg and diastolic BP < 95 mm Hg). After the completion of the Syst-Eur trial on 14 February 1997, 3506 consenting patients (93.0% of those eligible) were enrolled in phase 2 of the Syst-Eur trial. This open follow-up study aims to confirm the safety of long-term antihypertensive therapy based on a dihydropyridine. To lower the sitting systolic BP below 150 mm Hg (target BP), the first-line agent nitrendipine (10-40 mg/day) may be associated with enalapril (5-20 mg/day), hydrochlorothiazide (12.5-25 mg/day), both add-on study drugs, or if required any other antihypertensive agent. On 1 November 1998, 3248 patients were still being followed, 86 patients had proceeded to non-supervised follow-up, and 43 had died. The median follow-up in Syst-Eur 2 was 14.3 months. At the last available visit, systolic/diastolic BP in the patients formerly randomised to placebo (n = 1682) or active treatment (n = 1824), had decreased by 13.2/5.2 mm Hg and by 4.6/1.6 mm Hg, respectively, so that the between-group BP difference was 1.7 mm Hg systolic (95% Ci: 0.8 to 2.6 mm Hg; P < 0.001) and 0.9 mm Hg diastolic (95% Cl: 0.4 to 1.5 mm mm Hg; P < 0.001). At the beginning of Syst-Eur 2, the goal BP was reached by 25.4% and 50.6% of the former placebo and active-treatment groups; at the last visit these proportions were 55.9% and 63.1%, respectively. At that moment, 45.9% of the patients were on monotherapy with nitrendipine, 29.3% took nitrendipine in combination with other study drugs. Until the end of 2001, BP control of the Syst-Eur 2 patients will be further improved. Cardiovascular complications and adverse events, such as cancer or gastro-intestinal bleeding, will be monitored and validated by blinded experts.

Aged↗

Impact of obstetric factors on cord blood donation for transplantation.

Recent reports have shown that low nucleated cell dose significantly decreases survival after cord blood transplantation. Prior to starting clinical cord blood banking we investigated the impact of obstetric factors on cell dose and volume of cord blood donations. Cord blood was obtained from 114 normal full-term deliveries. Mean volume collected was 93.5 ml, mean total nucleated cell count (TNC) was 13.1 x 108. Statistical analysis was by backwards stepwise regression. Significant factors affecting nucleated cell yield were volume of blood collected (P < 0.001), length of gestation (P < 0. 0001), time from delivery of the infant to cord clamping (P = 0.018) and total length of labour (P = 0.002). In clinical cord blood banking we have successfully used these findings for pre-collection assessment of placentae. Out of 476 cord blood donations subsequently collected for banking, only 29 (6.1%) have been discarded due to low volume. The mean TNC of the 409 banked units following volume reduction was 10.1 x 108. Despite careful optimization of collection, processing and storage techniques, cell dose still limits cord blood transplantation to smaller recipients.

Blood Banks↗

Practitioner-centred research: an evaluation of the implementation of the bedside hand-over.

A practitioner-based enquiry (PBE) or 'practitioner-centred-research' (Rolfe 1998), was undertaken using action research to examine the concept of 'nursing hand-over'. The move away from the traditional style of hand-over (which involved either one or two people verbally relaying 'all' information to those nurses coming onto duty) to a hand-over that is based at the bedside with the patient and involves the patient and only those nurses accountable for that individual's care, was the focus of the study reported here. The study was carried out on a medical ward for people aged 65 and over and aimed to identify whether after 6 months (post-implementation of the new style of hand-over) all staff felt that key issues identified in a 3-month evaluation based primarily on quantitive data collection, had been addressed by using an action research methodology. Although reference will be made to the 3-month evaluation as it formed a vital part of the process of assessing the change to practice, the focus of the analysis will be the evaluation that took place after 6 months. The key objective was to assess the effectiveness of the planned implementation of hand-over at the bedside and the subsequent change to current nursing practice.

Aged↗

Clinical management of prolactinomas.

Prolactinomas are benign, sporadic pituitary tumours that typically present with amenorrhoea and galactorrhoea in women, and hypogonadism and space-occupying effects in men. Hyperprolactinaemic hypogonadism in either sex is associated with reduced bone mineral density, which may be progressive and only partially reversible. For most microprolactinomas, dopamine agonists are the treatment of choice, achieving normoprolactinaemia and restoring gonadal function in 80-90% of cases. Trans-sphenoidal surgery is curative in 60%, but may be complicated by hypopituitarism and is usually reserved for patients with dopamine agonist intolerance or resistance. A subgroup of patients with small tumours, mild symptoms and normal gonadal function may be monitored without specific treatment--the risk of tumour expansion is small. Macroprolactinomas should be treated medically, dopamine agonists controlling prolactin secretion and achieving significant tumour shrinkage in 80% of cases, whereas surgery is curative in only a quarter. Cabergoline is the dopamine agonist of choice in most situations, being better tolerated and more effective than bromocriptine. Quinagolide is an effective alternative. Dopamine agonist withdrawal or dose reduction should be considered after 2-5 years therapy. Oestrogens may be used with caution in women with prolactinomas.

Bone Density↗

An innovative professional nursing practice model.

Nursing, as with health care delivery, is changing to meet the greater challenges brought about by managed care and the accompanying external forces in the marketplace. Nurses, with their vast resources of knowledge and experience, are crucial in achieving optimal quality care. Given the opportunity to redefine and strengthen the impact of nursing practice at Piedmont Medical Center in Atlanta, Georgia, a group of advanced practice nurses began developing a unique practice model. The resulting Professional Nursing Practice Model--a theoretical framework created for nurses by nurses--presents a common vision of human beings, health, and nursing in accordance with the values and beliefs of nursing. This model demonstrates the importance of a person-centered, value-driven nursing practice across the continuum of health from birth to death.

Empathy↗

Guidelines for the diagnosis and treatment of hyperprolactinemia.

Hyperprolactinemia is the most common endocrine disorder of the hypothalamic-pituitary axis. While it can occur in men, it occurs more commonly in women. The prevalence of hyperprolactinemia ranges from 0.4% in an unselected normal adult population to as high as 9-17% in women with reproductive disorders. There are many possible causes of hyperprolactinemia, falling into three general categories: physiologic, pharmacologic and pathologic. When specific treatable underlying causes have been eliminated and in cases of severe hyperprolactinemia, the most likely cause is a prolactin (PRL)-secreting pituitary adenoma. Microadenomas should be treated medically, with a dopamine agonist, if there is an indication for therapy (such as amenorrhea, infertility or bothersome galactorrhea). If there is no indication for therapy, microadenomas may be followed conservatively, as growth is uncommon. Macroadenomas may grow larger; medical therapy is recommended initially, with neurosurgical evaluation reserved for specific clinical situations, such as failure of medical therapy and evidence of mass effect despite medical therapy. In the United States, the dopamine agonists indicated for treatment of hyperprolactinemia are bromocriptine and cabergoline. Bromocriptine is usually given once or twice daily, while cabergoline has a long duration of action and is given once or twice weekly. Results of comparative studies indicate that cabergoline is clearly superior to bromocriptine in efficacy (PRL suppression, restoration of gonadal function) and tolerability.

Adult↗

Dopamine agonist therapy in hyperprolactinemia.

Introduction of the dopamine agonist bromocriptine heralded a major advance in the management of hyperprolactinemic disorders. Although its side effects of nausea, dizziness and headache and its short elimination half-life are limiting factors, its efficacy established it as a reference compound against the activity of which several dopamine agonists, like pergolide, lysuride, metergoline, terguride and dihydroergocristine, fell by the wayside. More recently, two new agents, cabergoline and quinagolide, have been introduced and appear to offer considerable advantages over bromocriptine. Cabergoline, an ergoline D2 agonist, has a long plasma half-life that enables once- or twice-weekly administration. Quinagolide, in contrast, is a nonergot D2 agonist with an elimination half-life intermediate between those of bromocriptine and cabergoline, allowing the drug to be administered once daily. Comparative studies indicate that cabergoline is clearly superior to bromocriptine in efficacy (prolactin suppression, restoration of gonadal function) and in tolerability. In similar studies, quinagolide appeared to have similar efficacy and superior tolerability to that of bromocriptine. Results of a small crossover study indicate that cabergoline is better tolerated, with a trend toward activity superior to that of quinagolide. In hyperprolactinemic men and in women not seeking to become pregnant, cabergoline may be regarded as the treatment of choice.

Aminoquinolines↗

Lack of evidence for direct involvement of NMDA receptors or polyamines in blood-brain barrier injury after cerebral ischemia in rats.

It is hypothesized that after various types of brain injury, blood-brain barrier (BBB) opening and vasogenic edema result from excessive neuronal release of glutamate and stimulation of capillary N-methyl-d-aspartate (NMDA) receptors linked to polyamine (putrescine) synthesis in endothelial cells. We produced cerebral ischemia in rats and measured BBB opening 6 h later as the increase in regional transfer constants (Ki) for blood to brain diffusion of [3H]sucrose. Such BBB opening was not mitigated by drugs which block NMDA receptors (MK801 or AR-R 15896AR) or polyamine synthesis (difluoromethylornithine). These results question generality of the capillary NMDA receptor/polyamine hypothesis.

Animals↗

Prevention of dementia in randomised double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial.

BACKGROUND: Systolic hypertension increases the risk of dementia in elderly people. The vascular dementia project, set up in the framework of the double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial, investigated whether antihypertensive drug treatment could reduce the incidence of dementia. METHODS: Eligible patients had no dementia, were at least 60 years old, and had a blood pressure when seated of 160-219 mm Hg systolic and below 95 mm Hg diastolic. Active treatment consisted of nitrendipine (10-40 mg/day) with the possible addition of enalapril (5-20 mg/day), hydrochlorothiazide (12.5-25 mg/day), or both drugs, titrated or combined to reduce the systolic blood pressure by at least 20 mm Hg to reach a value below 150 mm Hg. Cognitive function was assessed by the mini mental state examination (MMSE). If the MMSE score was 23 or less, diagnostic tests for dementia were done (DSM-III-R criteria). The cause of dementia was established by the modified ischaemic score with brain imaging or the Hachinski score. FINDINGS: Median follow-up by intention to treat was 2.0 years. Compared with placebo (n=1180), active treatment (n=1238) reduced the incidence of dementia by 50% from 7.7 to 3.8 cases per 1000 patient-years (21 vs 11 patients, p=0.05). The median MMSE score at randomisation was 29 in both treatment groups. At the last available assessment, systolic and diastolic blood pressure were, respectively, 8.3 mm Hg and 3.8 mm Hg lower (p<0.001) in the active-treatment group, but on average the MMSE scores did not change in either group. In the control patients, however, the MMSE decreased (p=0.04) with decreasing diastolic blood pressure, whereas in the active-treatment group MMSE scores improved slightly (p=0.01) with greater reduction in diastolic blood pressure (p=0.002 for between-group difference). INTERPRETATION: In elderly people with isolated systolic hypertension, antihypertensive treatment was associated with a lower incidence of dementia. If 1000 hypertensive patients were treated with antihypertensive drugs for 5 years 19 cases of dementia might be prevented.

Aged↗

Temporal profiles of appearance of DNase I hypersensitive sites associated with the ovine beta-lactoglobulin gene differ in sheep and transgenic mice.

The ovine milk protein beta-lactoglobulin is expressed in a distinct temporal pattern during lactogenesis. This expression pattern is reflected in the temporal profile of appearance of DNase I hypersensitive sites (HS) associated with the beta-lactoglobulin gene in the mammary gland. Specifically, HSIV and HSV are present prior to the first major increase in expression, which occurs at mid-pregnancy, while HSI displays the converse profile, being detected after mid-pregnancy and during lactation. The extent of DNase I digestion at HSIII, encompassing the promoter region, reflects the level of beta-lactoglobulin expression. In transgenic mouse mammary chromatin, beta-lactoglobulin transgenes display the same set of DNase I hypersensitive sites as in sheep mammary chromatin. The temporal profile, however, differs from that seen in sheep: notably, HSIV and HSV are detected during lactation. The fact that beta-lactoglobulin transgenes lacking HSIV and HSV are expressed but display a reduced transcription rate per integrated copy is compatible with a functional role for these regions. This suggests that HSIV and HSV may increase the likelihood of high-level transgene expression.

Animals↗

Lipoprotein composition and serum apolipoproteins in normoglycaemic first-degree relatives of non-insulin dependent diabetic patients.

Cardiovascular disease is the leading cause of death in non-insulin dependent diabetes mellitus and first degree relatives of such patients are at increased risk of developing diabetes and cardiovascular disease. The aim of the present study was to determine whether lipid abnormalities occur in normoglycaemic relatives of non-insulin dependent diabetic patients. Cholesterol, triglycerides, apolipoprotein A-I and apolipoprotein B concentrations were measured in serum; the lipoprotein fractions very low density, intermediate density, low density and high density lipoprotein were prepared by sequential flotation ultracentrifugation and their composition investigated. The groups were matched for age, sex and blood glucose concentrations although the relatives (n = 126) were more insulin resistant as determined using the homeostasis model assessment method [1.9 (0.8-9.0) vs 1.6 (0.4-4.9) mmol/mU per l (mean [95% confidence intervals]); p < 0.001] and had greater body mass indices [26.6 (4.1) vs 24.8 (3.9) (mean [S.D.]); p = 0.001] than control subjects (n = 126). Relatives had higher serum apolipoprotein B concentrations than control subjects [0.9 (0.3) vs 0.8 (0.3) g/l, p = 0.02) and lower serum apolipoprotein A-I concentrations (1.4 (0.3) vs 1.5 (0.3), p = 0.02). In multivariate linear regression analysis of all subjects log insulin resistance (p = 0.0001), age (p = 0.002) and waist:hip ratio (p = 0.01) were independent predicators of apolipoprotein B concentrations while waist:hip ratio (p < 0.001) and smoking status (p = 0.002) were independent predictors of apolipoprotein A-I concentrations. Lipoprotein composition (measured in a subgroup of 76 control subjects and 88 relatives), serum cholesterol and serum triglyceride concentrations did not differ between the groups. We conclude that atherogenic apolipoprotein abnormalities occur in normoglycaemic relatives of non-insulin dependent diabetic patients.

Adult↗