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Biomedical subjects

C Eastwood

Publications and source records attributed to C Eastwood.

17 recordsLinked to original sources
PubMed2002

Energy intakes of institutionalised and free-living older people.

Inadequate energy intake is common in older adults, especially in those living in institutions. Underweight in older people is associated with increased risk of morbidity and mortality. The objective of this study was to compare energy and percentage of total energy from protein, fat, carbohydrate and alcohol between institutionalised (INS) and free-living (FL) older people. 16 INS volunteers (mean age 88 years, 20% male) and 23 FL volunteers (mean age 75 years, 48% male) were recruited. Food intake was measured using the 4-day weighed inventory method. Nutritional analysis was carried out using the computer program Dietplan5 for Windows. Energy intakes were significantly lower in the INS group compared with the FL group, due to the lower amount of food eaten. The energy intakes in the INS group were below the Estimated Average daily Requirement (1). The energy derived from fat was higher and the energy derived from carbohydrate lower than dietary recommendations in the INS group.

Activities of Daily Living↗
PubMed2000

Opioid-receptor-mediated excitation of rat mesenteric afferent fibres supplying the rat jejunum.

The aim of the present study was to examine the sensitivity to opioid-receptor agonists of mesenteric afferents supplying the small intestine and to characterize the subpopulations of any responsive fibres. Mesenteric afferent discharge was recorded electrophysiologically in response to cumulative doses (1-400 microgram kg-1) of the mu-receptor agonist [D-ala,2 N- me-Phe4, Gly5-ol]-enkephalin (DAMGO), the delta-receptor agonist [D-ala,2 D-leu5]-enkephalin (DADLE) and the kappa-receptor agonist U-50488. DAMGO and DADLE, but not U-50488, markedly stimulated whole nerve mesenteric afferent discharge (P < 0.05) that was unrelated to intestinal motor events. Subpopulations of afferent fibres responding to DAMGO were examined using waveform analysis to identify single units from within the whole mesenteric nerve bundles. One population was CCK-sensitive (15/15 fibres) and the other was a subpopulation of mechanosensitive afferents that responded to distension (17/28). 5-HT-sensitive afferents did not respond to DAMGO (0/11). We conclude that specific subpopulations of mesenteric afferents respond to mu- and possibly delta- but not kappa-receptor agonists. This sensitivity to opioids may contribute to the antinociceptive property of vagal afferents.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed2000

5-HT(3) and histamine H(1) receptors mediate afferent nerve sensitivity to intestinal anaphylaxis in rats.

BACKGROUND & AIMS: The mechanisms underlying brain stem activation during antigen challenge have not been resolved. Our aim was to characterize afferent nerve responses to intestinal anaphylaxis and determine the mediators involved in afferent activation. METHODS: Mesenteric afferent discharge was recorded electrophysiologically after intestinal anaphylaxis in anesthetized rats previously sensitized to chicken egg albumin (EA). RESULTS: Mesenteric afferent nerve discharge increased approximately 1 minute after luminal antigen but not bovine serum albumin (P < 0.001, EA vs. bovine serum albumin). Subsequent administration of antigen had no effect, but systemic EA evoked a marked increase in afferent discharge (P < 0. 05). Afferent responses were unrelated to intestinal motor activity, and the response to luminal antigen was attenuated by luminal anesthetic (1% lidocaine). The 5-HT(3)-receptor antagonist alosetron (30 microg. kg(-1)) and the histamine H(1)-receptor antagonist pyrilamine (5 mg. kg(-1)) markedly attenuated the response to luminal antigen; pretreatment with doxantrazole attenuated responses to both luminal and systemic antigen. CONCLUSIONS: 5-HT(3) and histamine, released from mast cells after intestinal anaphylaxis, stimulate mesenteric afferents via 5-HT(3) and histamine H(1) receptors. Information on intestinal immune status is rapidly relayed to the central nervous system and may play a role in neural reflexes and behavioral responses following activation of the immune system.

Anaphylaxis↗
PubMed1998

The role of endogenous cholecystokinin in the sensory transduction of luminal nutrient signals in the rat jejunum.

Some vagal afferent fibres are exquisitely sensitive to exogenous administration of cholecystokinin (CCK) but their sensitivity to endogenous CCK released by luminal stimuli has not been demonstrated directly, although implied from reflex and behavioural studies. We have therefore utilised electrophysiological techniques to record afferent discharge in mesenteric nerve bundles supplying the rat jejunum in response to luminal application of casein acid hydrolysate (CAH). CAH stimulated whole nerve afferent discharge in both in vivo and in vitro preparations (P < 0.01) while single unit analysis revealed that fibres sensitive to CAH also responded to exogenous CCK. The responses to both CCK and CAH were abolished by the CCKA antagonist devazepide. This study therefore supports the hypothesis that a functional relationship exists between CCK-containing enteroendocrine cells and the afferent fibres whose terminals lie within close proximity.

Afferent Pathways↗
PubMed1998

Characterization of adenosine receptors evoking excitation of mesenteric afferents in the rat.

We examined the effects of adenosine receptor agonists and antagonists on the discharge of mesenteric afferent nerves supplying the jejunum in pentobarbitone sodium-anaesthetized rats. Adenosine (0.03-10 mg kg(-1), i.v.), NECA (0.3-300 microg kg(-1), i.v.) and the A1 receptor agonist, GR79236 (0.3-1000 microg kg(-1), i.v.), each induced dose-dependent increases in afferent nerve activity and intrajejunal pressure, hypotension and bradycardia. The A1 receptor antagonist, DPCPX (3 mg kg(-1), i.v.), antagonized all the effects of GR79236 but only the haemodynamic effects of adenosine and NECA. The A2A receptor antagonist, ZM241385 (3 mg kg(-1), i.v.), antagonized the hypotensive effect of NECA but none of the effects of GR79236. The A2A receptor agonist, CGS21680 (0.3-300 microg kg(-1), i.v.), and the A3 receptor agonist, IB-MECA (0.3-300 microg kg(-1), i.v.), each induced only a dose-dependent hypotension. Subsequent administration of adenosine (3 mg kg(-1), i.v.) induced increases in afferent nerve activity and intrajejunal pressure and bradycardia. ZM241385 (3 mg kg(-1), i.v.) antagonized the hypotensive effect of CGS21680 but not the effects of adenosine. Bethanechol (300 microg kg(-1), i.v.) evoked increases in afferent nerve activity and intrajejunal pressure, hypotension and bradycardia. However, adenosine (3 mg kg(-1), i.v.) evoked greater increases in afferent nerve activity than bethanechol despite inducing smaller increases in intrajejunal pressure. In summary, A1 and A2B and/or A2B-like receptors evoke adenosine-induced increases in mesenteric afferent nerve activity and intrajejunal pressure in the anaesthetized rat. Furthermore, elevations in intrajejunal pressure do not wholly account for adenosine-evoked excitation of mesenteric afferent nerves.

Adenosine↗
PubMed1998

A 1-year community-based health economic study of ciprofloxacin vs usual antibiotic treatment in acute exacerbations of chronic bronchitis: the Canadian Ciprofloxacin Health Economic Study Group.

OBJECTIVE: To evaluate the costs, consequences, effectiveness, and safety of ciprofloxacin vs standard antibiotic care in patients with an initial acute exacerbation of chronic bronchitis (AECB) as well as recurrent AECBs over a 1-year period. DESIGN: Randomized, multicenter, parallel-group, open-label study. SETTING: Outpatient general practice. PATIENTS: A total of 240 patients, 18 years or older with chronic bronchitis, with a history of frequent exacerbations (three or more in the past year) presenting with a type 1 or 2 AECB (two or more of increased dyspnea, increased sputum volume, or sputum purulence). MAIN OUTCOME MEASURES: The assessment included AECB symptoms, antibiotics prescribed, concomitant medications, adverse events, hospitalizations, emergency department visits, outpatient resources such as diagnostic tests, procedures, and patient and caregiver out-of-pocket expenses. Patients completed the Nottingham Health Profile, St. George's Respiratory Questionnaire, and the Health Utilities Index. The parameters were recorded with each AECB and at regular quarterly intervals for 1 year. These variables were compared between the ciprofloxacin-treated group and the usual-care-treated group. RESULTS: Patients receiving ciprofloxacin experienced a median of two AECBs per patient compared to a median of three AECBs per patient receiving usual care. The mean annualized total number of AECB-symptom days was 42.9+/-2.8 in the ciprofloxacin arm compared to 45.6+/-3.0 days in the usual-care arm (p=0.50). The overall duration of the average AECB was 15.2+/-0.6 days for the ciprofloxacin arm compared to 16.3+/-0.6 days for the usual-care arm. Treatment with ciprofloxacin tended to accelerate the resolution of all AECBs compared to usual care (relative risk=1.20; 95% confidence interval [CI], 0.91 to 1.58; p=0.19). Treatment assignment did not affect the interexacerbation period but a history of severe bronchitis, prolonged chronic bronchitis, and an increased number of AECBs in the past year were associated with shorter exacerbations-free periods. There was a slight, but not statistically significant, improvement in all quality of life measures with ciprofloxacin over usual care. The only factors predictive of hospitalization were duration of chronic bronchitis (odds ratio=4.6; 95% CI, 1.6, 13.0) and severity of chronic bronchitis (odds ratio=4.3; 95% CI, 0.8, 24.6). The incremental cost difference of $578 Canadian in favor of usual care was not significant (95% CI, -$778, $1,932). The cost for the ciprofloxacin arm over the usual care arm was $18,588 Canadian per quality-adjusted life year gained. When the simple base case analysis was expanded to examine the effect of risk stratification, the presence of moderate or severe bronchitis and at least four AECBs in the previous year changed the economic and clinical analysis to one favorable to ciprofloxacin with the ciprofloxacin-treated group having a better clinical outcome at lower cost ("win-win" scenario). CONCLUSIONS: Treatment with ciprofloxacin tended to accelerate the resolution of all AECBs compared to usual care; however, the difference was not statistically significant. Further, usual care was found to be more reflective of best available care rather than usual first-line agents such as amoxicillin, tetracycline, or trimethoprim-sulfamethoxazole as originally expected. Despite the similar antimicrobial activities and broad-spectrum coverage of both ciprofloxacin and usual care, the trends in clinical outcomes and all quality of life measurements favor ciprofloxacin. In patients suffering from an AECB with a history of moderate to severe chronic bronchitis and at least four AECBs in the previous year, ciprofloxacin treatment offered substantial clinical and economic benefits. In these patients, ciprofloxacin may be the preferred first antimicrobial choice.

Adolescent↗
PubMed1996

Sensitivity of vagal mucosal afferents to cholecystokinin and its role in afferent signal transduction in the rat.

1. Extracellular recordings from rat mesenteric paravascular nerve bundles were made in order to characterize the responses of different populations of afferents supplying the small intestine to intravenous cholecystokinin (CCK; in the form of sulphated CCK8). 2. Approximately 70% of mesenteric nerve bundles contained CCK-sensitive afferent fibres. Responsive afferents had low spontaneous discharge (1.6 +/- 0.3 impulses s-1) and showed a 14-fold increase in firing at the peak of the response to 50 pmol CCK with the overall response lasting several minutes. The onset of the response occurred after a latency of (3.9 +/- 0.1 s) following i.v. administration of CCK, which corresponds largely to the circulation delay in these animals. The threshold dose of CCK was < 5 pmol. 3. The response to 100 pmol CCK was completely abolished by devazepide (0.5 mg kg-1) and by chronic subdiaphragmatic vagotomy performed 10-14 days prior to experimentation, indicating that CCK sensitivity was via CCKA receptors and exclusively mediated via vagal afferents rather than splanchnic or enteric afferents. 4. Evidence that CCK-sensitive afferents had mucosal receptive fields was indicated by the lack of any response to luminal distension and the sensitivity of the CCK response to luminal anaesthesia. Furthermore, CCK-sensitive afferents responded to luminal hydrochloric acid (50 mM) in a slowly adapting manner. The response to acid was significantly reduced (P < 0.005), but not abolished, by devazepide at a time when the response to exogenous CCK had been completely eliminated. 5. The exquisite sensitivity of some vagal mucosal afferents to CCK suggests that they may play a physiological role in the reflex and behavioural consequences of CCK release from the small intestine, possibly acting in a paracrine fashion. However, this sensitivity to CCK represents only one aspect of the broad chemosensitivity of these mucosal afferents and is not an obligatory component of the signal transduction pathway.

Afferent Pathways↗
PubMed1993

Definition and measurement of restenosis after successful coronary angioplasty: implications for clinical trials.

Angiographic restenosis represents the most established measure of long-term outcome in most prospective clinical trials of coronary angioplasty (PTCA). The accuracy of assessing this endpoint is of utmost importance. The purpose of this article is to propose guidelines for the use of coronary angiography in this setting. First, the cineangiograms must be of high technical quality and performed in a high proportion of consecutive patients in follow-up under controlled study conditions that are reproducible. Second, computer-assisted quantitative coronary angiographic analysis is essential to minimize interobserver and intraobserver variability in stenosis measurement between successive studies. The following recommendations are presented for quantitative coronary angiographic analysis. Because biplane orthogonal views cannot always be performed both at baseline and at follow-up, stenosis measurement in the single-plane, most severe view often constitutes the most consistent and practical approach. The edge-detection method is still much more reproducible and accurate than densitometry and should be the preferred method of analysis. Measurement of reference diameter by the interpolated method is more objective than measurement by the user-defined approach and should be used whenever possible. Finally, measurements of absolute minimum diameter and percent diameter stenosis are both important in the assessment of outcome in clinical trials. Absolute minimum diameters are independent of variations in reference diameter, and the extent of reduction in minimum diameter between the immediate postangioplasty and follow-up angiograms, when expressed in dichotomous or continuous fashion, accurately defines the extent of vessel wall hyperplasia as an endpoint. On the other hand, vessel size corresponds in general to the size of myocardium subserved, and absolute changes do not take into account this physiologic fact. Therefore defining restenosis in terms of significant reduction in percent diameter stenosis is also a useful approach because of its clinical relevance. Thus clinical restenosis requires that a successfully dilated segment (< 50% diameter stenosis) show a > or = 50% diameter stenosis at follow-up angiography with, in addition, a meaningful degree of change, that is, exceeding 2 SDs of observer variability in quantitative measurements which, in our experience, translates into > or = 15% difference between early postangioplasty and follow-up angiography measurements.

Angioplasty, Balloon, Coronary↗
PubMed1993

Effect of a platelet activating factor antagonist, WEB 2086, on allergen induced asthmatic responses.

BACKGROUND: Platelet activating factor (PAF) has been implicated in the pathogenesis of airway hyperresponsiveness in asthma. The purpose of this study was to evaluate the effects of a selective PAF antagonist (WEB 2086), given in doses known to antagonise the effects of inhaled PAF in human subjects, on allergen induced early and late asthmatic responses and on airway hyperresponsiveness. METHODS: Eight atopic, mildly asthmatic subjects were studied during a screening period and two treatment periods. During the screening period subjects inhaled an allergen to which they were known to be sensitised and the response was measured as the fall in the forced expired volume in one second (FEV1) to show the presence of early (0-1 h) and late (3-7 h) asthmatic responses. On another day the subjects inhaled allergen diluent. During the treatment periods subjects inhaled allergen after one week's pretreatment with WEB 2086 (100 mg three times a day) or placebo administered in a randomised, double blind, crossover fashion. Histamine airway responsiveness was measured 24 hours before and 24 hours after allergen and the results were expressed as the provocative concentration causing a 20% fall in FEV1 (PC20). RESULTS: The maximal early asthmatic response after allergen with placebo treatment was 18.4% (SE 4.4%) and with WEB 2086 18.9% (4.4%). The maximal late response with placebo treatment was 21.7% (5.3%) and with WEB 2086 21.2% (3.0%). The log difference (before and after allergen) in histamine PC20 was 0.35 (0.06) after placebo treatment and 0.30 (0.1) after WEB 2086. CONCLUSIONS: These results indicate that one week of treatment with an orally administered PAF antagonist (WEB 2086) does not attenuate allergen induced early or late responses or airway hyperresponsiveness.

Administration, Oral↗
PubMed1991

Clinical, physiologic, anatomic and procedural factors predictive of restenosis after percutaneous transluminal coronary angioplasty.

In a recent prospective double-blind placebo-controlled trial, a combination of aspirin and dipyridamole was not associated with a reduction in the rate of restenosis within the 1st 6 months after coronary angioplasty. The purpose of this study was to determine whether clinical, anatomic or procedural factors were predictive of the observed restenosis rates in that prospective trial. A total of 247 patients and 280 segments underwent follow-up angiography and quantitative coronary angiographic analysis between 4 and 7 months after coronary angioplasty. Two baseline clinical characteristics--angina class and duration of angina in months--were related to the rate of restenosis by univariate analysis. Patient-related stepwise logistic regression analysis identified severity of angina as the only clinical predictor of restenosis. Three univariate baseline anatomic characteristics--percent diameter stenosis before angioplasty, stenosis greater than 10 mm in length and calcific stenosis--and two early postangioplasty characteristics--residual percent diameter stenosis and residual mean pressure gradient--were predictive of restenosis. Of these, only two--length of stenosis and residual percent diameter stenosis--were independently related to restenosis by multivariate analysis and only the former is identifiable before the procedure. It is concluded that in prospective studies in contrast to retrospective studies, few clinical and anatomic factors appear to be predictive of restenosis after coronary angioplasty.

Angioplasty, Balloon, Coronary↗
PubMed1990

Prevention of acute complications after percutaneous transluminal coronary angioplasty.

The prevention of major complications occurring during or early after percutaneous transluminal coronary angioplasty was evaluated in 376 patients in a randomized, double-blind, placebo-controlled multicenter trial. Starting 24 hours before angioplasty, 187 patients received an aspirin-dipyridamole combination and 189 were given placebo. There were no periprocedural deaths. Periprocedural non-fatal myocardial infarction was diagnosed in 34 patients (9.0%). Q wave myocardial infarction occurred in 16 patients: 3 (1.6%) in the aspirin-dipyridamole group and 13 (6.9%) in the placebo group (p = 0.0113). Non-Q wave myocardial infarction occurred in 18 patients: 6 (3.2%) in the active drug group and 12 (6.3%) in the placebo group (p = 0.1538). Emergency myocardial revascularization was performed in 9 patients in each treatment arm. Q wave myocardial infarction occurred following revascularization in 5 patients (55.5%) in the placebo group and in only 2 (22.2%, p = 0.1670) in the aspirin-dipyridamole group. Thus the incidence of periprocedural Q and non-Q wave myocardial infarction is high in patients not on antiplatelet therapy (13.2%) and is markedly lower in those on the aspirin-dipyridamole combination (4.8%, p = 0.0044). Short-term antiplatelet therapy before and after angioplasty can be recommended for patients who do not have contraindications to this medication.

Acute Disease↗
PubMed1990

The role of antiplatelet agents in modifying the extent of restenosis following percutaneous transluminal coronary angioplasty.

We previously reported that a combination of aspirin and dipyridamole given before, during, and for 6 months following percutaneous transluminal coronary angioplasty (PTCA) did not reduce the incidence of restenosis. In that trial, a total of 272 successfully dilated segments in 243 patients reached final quantitative angiography and of these, 86 segments (31.6%) had restenosed (46 of 130 segments in the group of patients given placebo and 40 of 142 segments in the aspirin-dipyridamole group). A secondary analysis of these 86 segments revealed that at follow-up angiography the severity of restenosis was greater in the 46 segments in the placebo group than in the 40 segments in the active treatment group (mean minimal luminal diameter at the stenosis = 0.76 +/- 0.52 and 1.03 +/- 0.45 mm, respectively, p = 0.01). The frequency of total or subtotal occlusions was higher in the placebo group (17.4%) than in the active treatment group (5.0%), but this observation did not reach statistical significance (p = 0.07). Although long-term treatment with aspirin and dipyridamole after successful PTCA does not reduce the incidence of recurrence, this secondary analysis suggests that it is associated with a decreased likelihood of severe restenosis.

Adult↗
PubMed1975

The effect of high and low doses of cycloheximide on nucleolar ribonucleic acid synthesis.

In resting rat liver a dose of cycloheximide (1 mg. per kg.) inhibits leucine incorporation by 80 per cent whereas doses above 15 mg. per kg. inhibit it more than 90 per cent, when tested at 90 minutes following intraperitoneal injection. Initial stimulation of incorporation of orotate into total cellular, nuclear, and nucleolar fractions was seen at all doses tested. After 3 hours, however, marked suppression of incorporation particularly into nucleolar RNA was seen at 5 mg. per kg. and above while 1 mg. per kg. continued to stimulate. At 5 hours there was continued marked inhibition of RNA synthesis by 30 mg. per kg. and slight depression of RNA synthesis even by 1 mg. per kg. Preliminary ultrastructural studies failed to show objective nucleolar alterations even after 5 hours of cycloheximide treatment at a dose of 30 mg. per kg. No direct effect of several concentrations of cycloheximide on RNA synthesis was seen in an in vitro nucleolar system.

Animals↗