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Biomedical subjects

M Forrest

Publications and source records attributed to M Forrest.

At least 19 recordsLinked to original sources

Remifentanil infusion in association with fentanyl-propofol anaesthesia in patients undergoing cardiac surgery: effects on morphine requirement and postoperative analgesia.

BACKGROUND: We have prospectively assessed the effects of remifentanil on morphine requirement in the first hour after emerging from general anaesthesia after elective coronary artery bypass surgery and in the first 12 h postoperatively, and pain and agitation scores in the first hour after emerging from general anaesthesia. METHODS: Twenty patients undergoing off-pump coronary artery bypass surgery, receiving standardized propofol-fentanyl-based anaesthesia, randomly received infusions of either remifentanil 0.1 microg kg(-1) min(-1) (Group R, n=10) or saline (Group S, n=10), each infused at 0.12 ml kg(-1) h(-1). Propofol and trial drug infusion were continued into the postoperative period until the patients were ready to be woken up. Postoperative analgesia was provided with morphine infusion commenced immediately after operation, and was additionally nurse controlled on the basis of a visual analogue scale (VAS) score (0-10). Agitation score was recorded using a VAS of 0-3. RESULTS: In the first hour after discontinuing propofol and trial infusion, morphine requirements were significantly higher in the remifentanil group (8.15 (sd 3.59) mg) compared with the saline group (3.29 (2.36) mg) (P<0.01). There was no difference in the total morphine given during the period after stopping propofol or in the total requirement in the first 12 h postoperatively. There was no significant difference in either pain scores or agitation scores between the two groups. CONCLUSION: Use of remifentanil is associated with increased opioid requirement in the first hour after it has been discontinued.

Adult↗

Immune cell regulation and cardiovascular effects of sphingosine 1-phosphate receptor agonists in rodents are mediated via distinct receptor subtypes.

Sphingosine 1-phosphate (S1P) is a bioactive lysolipid with pleiotropic functions mediated through a family of G protein-coupled receptors, S1P(1,2,3,4,5). Physiological effects of S1P receptor agonists include regulation of cardiovascular function and immunosuppression via redistribution of lymphocytes from blood to secondary lymphoid organs. The phosphorylated metabolite of the immunosuppressant agent FTY720 (2-amino-2-(2-[4-octylphenyl]ethyl)-1,3-propanediol) and other phosphonate analogs with differential receptor selectivity were investigated. No significant species differences in compound potency or rank order of activity on receptors cloned from human, murine, and rat sources were observed. All synthetic analogs were high-affinity agonists on S1P(1), with IC(50) values for ligand binding between 0.3 and 14 nM. The correlation between S1P(1) receptor activation and the ED(50) for lymphocyte reduction was highly significant (p < 0.001) and lower for the other receptors. In contrast to S1P(1)-mediated effects on lymphocyte recirculation, three lines of evidence link S1P(3) receptor activity with acute toxicity and cardiovascular regulation: compound potency on S1P(3) correlated with toxicity and bradycardia; the shift in potency of phosphorylated-FTY720 for inducing lymphopenia versus bradycardia and hypertension was consistent with affinity for S1P(1) relative to S1P(3); and toxicity, bradycardia, and hypertension were absent in S1P(3)(-/-) mice. Blood pressure effects of agonists in anesthetized rats were complex, whereas hypertension was the predominant effect in conscious rats and mice. Immunolocalization of S1P(3) in rodent heart revealed abundant expression on myocytes and perivascular smooth muscle cells consistent with regulation of bradycardia and hypertension, whereas S1P(1) expression was restricted to the vascular endothelium.

Anesthesia↗

Lu 25-109, a muscarinic agonist, fails to improve cognition in Alzheimer's disease. Lu25-109 Study Group.

OBJECTIVE: To evaluate the therapeutic effect of the selective muscarinic receptor m1 partial agonist, m2 antagonist, Lu25-109-a compound that directly stimulates muscarinic cholinergic receptors-in patients with probable AD. METHODS: A 6-month, randomized, double-blind, placebo-controlled, parallel group trial comparing three doses of Lu25-109 with placebo was carried out. A total of 496 patients with probable AD with a Mini-Mental State Examination score between 10 and 26 were enrolled at 29 centers and randomized to placebo or Lu25-109 25, 50, or 100 mg tid. The primary efficacy measures were the AD Assessment Scale-Cognitive subscale and the AD Cooperative Study Clinical Global Impression of Change. Secondary efficacy variables included the AD Cooperative Study Inventory of Activities of Daily Living and the Behavioral Symptoms in AD Scale. RESULTS: In both an intent-to-treat and a completer's analysis there were no significant differences for either the two primary or the secondary variables. There was a trend for patients on the highest drug dose to worsen in the completer's analysis. Adverse events included dizziness, nausea, diarrhea, fatigue, increased sweating, and anorexia, all of which increased with increasing drug dose. CONCLUSION: Lu25-109, a selective partial ml agonist and an m2/m3 antagonist, failed to improve cognition in patients with mild to moderate AD.

Aged↗

The information needs of doctors-in-training: case study from the Cairns Library, University of Oxford.

The objective of this study was to find out more about the information needs of doctors-in-training and to identify their preferred sources of information. The methodology included interviews with consultants and administrators, a focus group discussion with library staff and a postal questionnaire sent to 347 doctors-in-training (there was a 43% return). The shortcomings of a questionnaire primarily composed of closed questions were addressed by the inclusion of one-to-one interviews which offered the opportunity for more in-depth commentary on specific issues highlighted in the questionnaire. Results indicated the frequency with which various types of information sources were consulted and how this related to the 'ease of access' of each information source. There was also the opportunity to comment on future information needs. It was clear from the interviews as well as comments made on the questionnaire that the two most important requirements for doctors-in-training were 'more time to find and obtain information' and 'better access to information sources when and where they are needed'. The results, although not surprising, included specific suggestions that have been used for the strategic planning of the library service to deliver the best possible support to users within the current framework of evidence-based medicine.

Education, Medical↗

Pre-exercise carbohydrate and fluid ingestion: influence of glycemic response on 10-km treadmill running performance in the heat.

BACKGROUND: The purpose of this study was to determine the influence of ingesting solutions containing mixtures of carbohydrate (CHO) types on pre-exercise glycemic response, exercise-induced hypoglycemia, metabolic responses, and 10-km treadmill running performance in a warm environment. METHODS: Ten trained runners completed 6, self-paced 10-km treadmill runs one hour after ingesting 900 ml of one of the following test solutions: a water placebo (WP), an 8 g 100 ml-1 high fructose corn syrup solution (HFG; 72 g CHO), a 6 g 100 ml-1 glucose solution (GLU; 54 g CHO), a 6 g.100 ml-1 sucrose/glucose mixture (SUG; 54 g CHO), or banana with water to equal 900 ml (BAN; approx. 54 g CHO). The sixth condition was 675 ml of an 8 g.100 ml-1 HFCS solution (LFG; 54 g CHO). Blood samples were taken prior to ingestion and every 15 min during rest and at 15 and 30 min, and at the end of the 10-km run. Blood was analyzed for glucose (BG) insulin (IN), glycerol, lactate, and percent change in plasma volume. Urine volume during the 1 hour of rest and change in body mass during exercise were also determined. RESULTS: A significant (p < 0.05) correlation (r = -0.684) was seen between the pre-exercise glycemic response (PEGR = area under the resting BG curve) and the change in BG from pre-EX to 15 min of exercise. BG at 15 min of exercise was significantly higher in the WP (5.22 mM) versus the other conditions (HFG = 3.32, LFG = 3.91, GLU = 3.38, BAN = 3.74 & SUG = 3.63 mM). Pre-exercise IN was lower in the WP (6.54 U ml-1) condition versus the other conditions (HFG = 22.1, LFG = 16.2, GLU = 23.3, BAN = 18.8 & SUG = 12.8 U.ml-1). Ten km performance times were not different (WP = 41.87, HFG = 41.66, LFG = 41.79, GLU = 41.65, BAN = 41.53, and SUG = 41.75 min). A significantly greater body mass loss occurred due to urine production during the 60 min of rest in the WP compared to the other conditions. The degree of exercise-induced decline in blood glucose was related to the PEGR; however, the decline in BG did not affect 10-km running performance. In addition, there were no differences in the metabolic responses during exercise between the different CHO types, nor did the type of CHO influence running performance. Finally, the presence of CHO and/or electrolytes in the hydration solutions produced a better fluid retention during the 60-min pre-exercise rest period compared to water. CONCLUSIONS: The results confirmed that if a competitive athlete consumed a breakfast prior to ingesting a CHO-electrolyte beverage, a practice that is common, the glycemic responses may be different.

Adult↗

A valuable tree by gum!

Which majestic ornamental tree, conspicuous in the Australian landscape, has ten million hectares in cultivation worldwide--yielding timber, fuel, essential oil and cut foliage? It could only be eucalyptus.

Australia↗

A simple method for the measurement of polymerization shrinkage in dental composites.

OBJECTIVE: In this study a simple non-contact method was developed to measure the polymerization shrinkage of dental composites. METHODS: A gas pycnometer was used to determine the volumes of specimens prior to and after photopolymerization and from which the total volumetric shrinkage could be determined. RESULTS: Four commercial composites were studied and were found to have polymerization shrinkages varying from 1.6 to 2.5%. The method was found to be labour efficient and produced reproducible results with a standard deviation of approximately 10%. SIGNIFICANCE: This method is appropriate for shrinkage measurements where only the total amount shrinkage is required and in particular for the measurement of shrinkage of photocured materials which are sensitive to water absorption.

Composite Resins↗

A bridging study of LU 25-109 in patients with probable Alzheimer's disease.

Lu 25-109 is a functionally selective partial M1 agonist with M2/M3 antagonist properties. This double-blind, placebo-controlled, two-part, inpatient bridging study was designed to evaluate the safety and tolerability of multiple oral doses of Lu 25-109 in patients with Alzheimer's Disease(AD), and to determine the maximum tolerated dose (MTD) in this population. In the first part of the study, the fixed-dose MTD was to be determined in five consecutive panels of 6 patients each (4 Lu 25-109/2 placebo). Doses for the five panels were 100, 125, 150, 200, and 225 mg tid for 7 days. Cholinergic adverse events such as increased salivation, dizziness, and gastrointestinal symptoms were observed at all doses studied. The dosing of fixed-dose panels was discontinued after 3 days at 200 mg tid due to unacceptable gastrointestinal adverse events. Thus, 150 mg tid was defined as the fixed-dose MTD. The second part of the study, conducted in a single panel of 8 patients (6 Lu 25-109/2 placebo), was designed to determine if patients could tolerate higher doses of Lu 25-109 when administered on a titration regimen. Patients were to receive doses that were 50%, 75%, 100%, 125%, and 150% of the fixed dose MTD, with dose increases every five days. The first dose, 75 mg tid, was very well-tolerated; however, as in the first phase of the study, patients did not tolerate the 200 mg tid dose. Thus, the titration regimen employed did not improve the overall tolerability of Lu 25-109.

Aged↗

Heart disease education and prevention program targeting immigrant Latinos: using focus group responses to develop effective interventions.

Although research has provided considerable knowledge concerning the positive effects of behavioral change on morbidity and mortality from heart disease and related risk factors, some segments of the population have not benefited equitably from this information. In April 1995, the National Heart, Lung, and Blood Institute (NHLBI) conducted seven focus groups to determine knowledge and attitudes about heart disease and associated risk factors, identify media usage and preferences, and assess publications usage and preferences among Spanish-speaking Latino immigrants residing in the Washington, D.C., metropolitan area. This information was gathered to assist in the development of key messages and strategies for the NHLBI Latino Community Cardiovascular Disease Prevention and Outreach Initiative, Salud para su Corazón--a heart disease prevention and education campaign. Findings from these focus groups indicate that Latinos may not benefit from heart disease prevention messages developed for the general population because of language and cultural differences. The researchers concluded that health education and disease prevention programs targeting the Latino community should develop educational materials and interventions that address language preferences and cultural values. Furthermore, to be effective, these programs should show people how to make positive behavioral changes based on their current circumstances, while remaining sensitive to the fact that Latino immigrants face major life adjustments and many are still greatly influenced by their country of origin.

Adolescent↗

Costing the library services. Cairns Library: a case study.

In the present climate libraries have to adopt a business approach to funding submissions; detailed management information must be produced in support of expenditure and to ensure that the services are cost-effective. In addition to the grant from its parent body (the Faculty of Clinical Medicine, University of Oxford), the Cairns Library obtains funding from five other bodies, including National Health Service Hospital Trusts. The Cairns Library has introduced an ongoing costing exercise covering the different services. The costs are divided into three categories: salary costs, other direct costs and indirect costs. Staff time has been identified from detailed time-sheets kept by each member of staff; the time recorded is assigned to the individual services. The direct costs and the indirect costs have been identified and allocated/apportioned similarly. The services are divided into five packages: core, current awareness, document delivery, enquiries and user education. The costs for each package have been apportioned to the funding bodies on the basis of the number of registered users from each body.

Cost Allocation↗

[Vascular surgery in patients with impaired renal function].

The purpose of the study was to evaluate the effect of surgery for renal artery stenosis in patients with impaired renal function. The design was a retrospective investigation with follow-up. The material consisted of 42 such patients operated at Rigshospitalet between 1980 and 1990. Renal function and blood pressure status was evaluated preoperatively and at follow-up. The perioperative mortality was 5% (n = 2) and morbidity 21% (n = 9). At discharge from hospital renal function was maintained in 38 patients (90%), including three patients who at the time of operation were without diuresis and had been in dialysis for up to 28 days. Twenty-three patients were still alive at postoperative follow-up at a median of 66 months. The cumulative five-year survival was 62%, which was significantly lower than that of a sex- and age-matched population. Eleven patients developed terminal renal insufficiency during the follow-up period. The cumulative preservation of renal function was 77% after five years. In conclusion, reconstruction of the renal arteries in patients with declining renal function and renal artery stenosis or occlusion can save renal function such that dialysis may be avoided in most cases.

Adult↗

[Surgical treatment of renovascular hypertension caused by renal artery stenosis. A retrospective study].

During a 10 year period 58 patients with renovascular hypertension due to renal artery stenosis were treated surgically. A retrospective analysis of the results was carried out. No perioperative mortalities occurred. Ten percent of the patients developed hypertension again after an average of 27 months. At follow-up (median 65 months), 85% of the patients had normal blood pressure or either no, modest or considerably reduced anti-hypertensive medication. It is concluded that surgical treatment of renovascular hypertension is a safe and effective procedure.

Adolescent↗

Microvascular oxidative stress preceding leukocyte activation elicited by in vivo nitric oxide suppression.

This study was aimed to determine the mechanism by which endogenous nitric oxide suppression promotes leukocyte adhesion in vivo. The rat mesenteric microcirculation was superfused with NG-nitro-L-arginine methyl ester (L-NAME; 100 microM), and intracellular oxidant formation in several microcirculatory cellular components such as arteriolar and venular endothelium and mast cells was visually monitored by digital microfluorography assisted by carboxydichlorofluorescein (CDCF), a hydroperoxide-sensitive fluorogenic probe. Adherent leukocyte density was measured simultaneously. L-NAME induced a significant time-dependent increase in CDCF fluorescence in arteriolar and venular endothelium and mast cells followed by firm adhesion of leukocytes. L-NAME-induced CDCF elevation showed a different spatial distribution compared with that evoked by N-formylmethionyl-leucyl-phenylalanine, in which only local venular segments with adhering leukocytes exhibited CDCF fluorescence enhancement. The level of hydroperoxide formation in arterioles and venules evoked by 60-min L-NAME superfusion was equivalent to that induced by the superfusion of approximately 880 microM tert-butyl hydroperoxide for 10 min. Pretreatment with anti-intracellular adhesion molecule-1, anti-P-selectin, or anti-CD18 monoclonal antibody attenuated L-NAME-elicited venular leukocyte adhesion without abolishing CDCF fluorescence in situ. Pretreatment with desferioxamine (50 mg/kg iv; 1 h before L-NAME superfusion) significantly diminished the iron-catalyzed hydroperoxide formation in arterioles and venules, but not in interstitial mast cells, as well as subsequent venular leukocyte adhesion. These findings indicate that endogenous nitric oxide may modulate oxidative stress in mast cells, arteriolar and venular microvascular endothelium and thereby can play a crucial role in leukocyte recruitment in venules.

Animals↗