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Biomedical subjects

A Pipe

Publications and source records attributed to A Pipe.

At least 19 recordsLinked to original sources

Identification of a potent and selective oxytocin antagonist, from screening a fully encoded differential release combinatorial chemical library.

A library of 1,296 1,4-benzodiazepines was prepared on 160 microM Tentagel beads. Compounds are attached to the beads using orthogonally cleavable linkers. The library was first screened as pools of 30 beads where 50% of the material is released and screened. GW405212X, a selective oxytocin antagonist, was identified by picking single beads from active pools.

Animals↗

Single bead and hard tag decoding using accurate isotopic difference target analysis-encoded combinatorial libraries.

A single fully automated generic microbore liquid chromatography electrospray time-of-flight protocol has been developed for the analysis of single beads, single beads with analytical constructs, and isotopically labelled dialkylamine hard tags. The protocol relies upon the incorporation of an isotopic signature into the linker and/or derivatising molecule to give a specific isotopic ratio together with an accurate isotopic difference. These properties facilitate highly specific and sensitive analysis of beads and hard tags using accurate isotopic difference analysis (AIDA) without prior knowledge of the molecular weight. Three open access methods with automated processing have been developed around a core generic approach.

Amines↗

Effects of a 21-day expedition to 6,194 m on human skeletal muscle SR Ca2+-ATPase.

We investigated the effects of a 21-day expedition to the summit of Mount Denali, Alaska (6,194 m) on selected Ca2+ sequestration properties of sarcoplasmic reticulum (SR) calcium pump in vastus lateralis muscle. Muscle samples were obtained by biopsy from 5 male climbers (peak oxygen consumption, VO2peak = 52.3 +/- 2.1 mL.kg(-1).min(-1)) approximately 7 days prior to (PRE) and 4 days following (POST) the expedition. A comparison of PRE versus POST measures of maximal Ca2+-ATPase activities (117 +/- 8.5 vs. 97.6 +/- 5.6 nmol.mg protein(-1).min(-1)) and Ca2+-uptake (204 +/- 15 vs. 161 +/- 11 nmol.mg protein(-1).min(-1)) measured in crude homogenates obtained from pre-exercised muscle, indicated only an effect (p < 0.05) of the expedition on Ca2+-uptake. The reduction in Ca2+-ATPase activity, representing 16.6%, was not significant (p = 0.089). The sarco endoplasmic reticulum calcium (SERCA)-ATPase isoforms, measured using Western blotting techniques, revealed a small reduction (p < 0.05) in SERCA 1 (-4.6 +/- 1.9%), but not in SERCA 2a (+2.0 +/- 1.4%). Prior to the expedition, both Ca2+-ATPase activity and Ca2+-uptake were reduced (p < 0.05) by approximately 34 and 18%, respectively, following 40 min of a two-step continuous cycling task (20 min at 59% VO2peak and 20 min at 74% VO2peak). The exercise-induced reduction in Ca2+-ATPase activity was independent of fiber type. Only in the case of Ca2+-uptake was a lower exercise response (p < 0.05) observed following the expedition, an effect that was due to the lower resting value. It is concluded that acclimatization as experienced during a mountaineering expedition induces changes in the properties of the SR Ca2+-pump, and particularly to Ca2+-sequestering function.

Acclimatization↗

Human skeletal muscle exercise metabolism following an expedition to mount denali.

Chronic exposure to high altitude is known to result in changes in the mechanisms regulating O(2) delivery to the contracting muscle. However, the effects of acclimatization on metabolism in the contracting muscle cell remain unclear. In this study, we have investigated the hypothesis that acclimatization would result in a closer coupling between ATP utilization and ATP production and that the improved energy state would be accompanied by a reorganization of the metabolic pathways consisting of an increased oxidative and decreased glycolytic potential. Five men, mean age of 28 +/- 2 (SE) yr, performed a standardized, two-stage submaximal cycling task in normoxia for 20 min at each of 59 and 74% peak O(2) consumption before and 3-4 days after returning from a 21-day expedition to Mount Denali (6,194 m). Acclimatization was without effect in altering the resting values of the adenine nucleotides (ATP, ADP, AMP), inosine monophosphate (IMP), or phosphocreatine (PCr) in the vastus lateralis. During exercise (40 min) after acclimatization compared with preacclimatization, PCr was not as depressed (33.2 +/- 7.1 vs. 40.6 +/- 5.4 mmol/kg dry wt) and IMP (0.289 +/- 0.11 vs. 0. 131 +/- 0.03 mmol/kg dry wt) and lactate (26.1 +/- 6.2 vs. 18.6 +/- 8.8 mmol/kg dry wt) in contracting muscle were not as elevated (P < 0.05). Although no effect of acclimatization was observed for the maximal activity (mol. kg protein(-1). h(-1)) of citrate synthase (4. 76 +/- 0.44 vs. 4.94 +/- 0.45), lactate dehydrogenase was increased by 13% (36.5 +/- 2.6 vs. 41.2 +/- 3.1, P < 0.05). It is concluded that acclimatization results in an improved energy state in the contracting muscle when tested under normoxic conditions; however, these effects are not associated with a higher oxidative potential or a lower glycolytic potential as hypothesized.

Acclimatization↗

Downregulation in muscle Na(+)-K(+)-ATPase following a 21-day expedition to 6,194 m.

To investigate the hypothesis that acclimatization to altitude would result in a downregulation in muscle Na(+)-K(+)-ATPase pump concentration, tissue samples were obtained from the vastus lateralis muscle of six volunteers (5 males and 1 female), ranging in age from 24 to 35 yr, both before and within 3 days after a 21-day expedition to the summit of Mount Denali, Alaska (6,194 m). Na(+)-K(+)-ATPase, measured by the [(3)H]ouabain-binding technique, decreased by 13.8% [348 +/- 12 vs. 300 +/- 7.6 (SE) pmol/g wet wt; P < 0.05]. No changes were found in the maximal activities (mol. kg protein(-1). h(-1)) of the mitochondrial enzymes, succinic dehydrogenase (3.63 +/- 0.20 vs. 3.25 +/- 0.23), citrate synthase (4. 76 +/- 0.44 vs. 4.94 +/- 0.44), and malate dehydrogenase (12.6 +/- 1. 8 vs. 12.7 +/- 1.2). Similarly, the expedition had no effect on any of the histochemical properties examined, namely fiber-type distribution (types I, IIA, IIB, IC, IIC, IIAB), area, capillarization, and succinic dehydrogenase activity. Peak aerobic power (52.3 +/- 2.1 vs. 50.6 +/- 1.9 ml. kg(-1). min(-1)) and body mass (76.9 +/- 3.7 vs. 75.5 +/- 2.9 kg) were also unaffected. We concluded that acclimatization to altitude results in a downregulation in muscle Na(+)-K(+)-ATPase pump concentration, which occurs without changes in oxidative potential and other fiber-type histochemical properties.

3-Hydroxyacyl CoA Dehydrogenases↗

Increases in submaximal cycling efficiency mediated by altitude acclimatization.

To investigate the hypothesis that respiratory gas exchange and, in particular, the O(2) consumption (VO(2)) response to exercise is altered after a 21-day expedition to 6,194 m, five male climbers (age 28.2 +/- 2 yr; weight 76.9 +/- 4.3 kg; means +/- SE) performed a progressive and prolonged two-step cycle test both before and 3-4 days after return to sea level. During both exercise tests, a depression (P < 0.05) in VO(2) (l/min) and an increase (P < 0.05) in minute ventilation (VE BTPS; l/min) and respiratory exchange ratio were observed after the expedition. These changes occurred in the absence of changes in CO(2) production (l/min). During steady-state submaximal exercise, net efficiency, calculated from the rates of the mechanical power output to the energy expended (VO(2)) above that measured at rest, increased (P < 0.05) from 25.9 +/- 1.6 to 31. 3 +/- 1.3% at the lighter power output and from 24.4 +/- 1.3 to 29.5 +/- 1.5% at the heavy power output. These changes were accompanied by a 4.5% reduction (P < 0.05) in peak VO(2) (3.99 +/- 0.17 vs. 3.81 +/- 0.18 l/min). After the expedition, an increase (P < 0.05) in hemoglobin concentration (15.0 +/- 0.49 vs. 15.8 +/- 0.41 g/100 ml) was found. It is concluded that, because resting VO(2) was unchanged, net efficiency is enhanced during submaximal exercise after a mountaineering expedition when the exercise is performed soon after return to sea level conditions.

Acclimatization↗

Is telephone counselling a useful addition to physician advice and nicotine replacement therapy in helping patients to stop smoking? A randomized controlled trial.

BACKGROUND: The authors evaluated the incremental efficacy of telephone counselling by a nurse in addition to physician advice and nicotine replacement therapy in helping patients to stop smoking. METHODS: The trial was conducted at the University of Ottawa Heart Institute. A total of 396 volunteers who smoked 15 or more cigarettes daily were randomly assigned to either of 2 groups: usual care (control group) and usual care plus telephone counselling (intervention group); the groups were stratified by sex and degree of nicotine dependence. Usual care involved the receipt of physician advice on 3 occasions, self-help materials and 12 weeks of nicotine replacement therapy. Telephone counselling was provided by a nurse at 2, 6 and 13 weeks after the target quit date. Point-prevalent quit rates were determined at 52 weeks after the target quit date. RESULTS: The point-prevalent quit rates at 52 weeks did not differ significantly between the control and intervention groups (24.1% v. 23.4% respectively). The quit rates did not differ significantly at the secondary measurement points of 4, 12 and 26 weeks. INTERPRETATION: Brief physician assistance, along with nicotine replacement therapy, can help well-motivated smokers to quit. Three additional sessions of telephone counselling by a nurse were ineffective in increasing quit rates. This form of assistance may be useful in the absence of physician advice or when self-selected by patients.

Adult↗

The ethics of blood testing as an element of doping control in sport.

Sport authorities continue to confront a variety of perplexing issues as they attempt to address effectively and efficiently the problems posed by doping. The emergence of the phenomena of blood doping and the administration of erythropoietin have added to the challenges faced by doping control authorities. Some sport organizations have introduced blood tests in an attempt to deal with these issues despite the absence of any effective test for the detection of the administration of homologous blood products or eythropoietin. A number of ethical issues are raised by such developments. Even in the presence of an effective test it is suggested that the decision to implement a specific testing approach can be reached by considering the wishes of a hypothetical "Fair Competitor" and an analysis of the costs involved. In this respect the Fair Competitor assumes in the sport community the role that the "reasonable person" occupies in law, permitting an analysis of a proposed course of action. In making any decision regarding the implementation of any test, a Fair Competitor would be guided by considerations of the postulated advantage and incidence of a doping technique, the likelihood of false positive and negative results, the risk of unwanted consequences of a testing process, and a concern that a specific test not accelerate the likelihood of the use of other doping methods. This approach is applied to a consideration of the appropriateness of blood testing in sport. It is concluded, using such an analysis, that in their present state of development, blood tests should not be implemented. It is recognized that certain sport authorities currently use blood tests to exclude competitors whose blood values exceed certain predetermined levels on the grounds of concerns regarding health and safety. Screening of this kind is beyond the purview of this discussion.

Doping in Sports↗

Smoking.

Explore the source record for details and available documents.

Adolescent↗

Coagulation factor changes following endurance exercise.

OBJECTIVE: To compare preexercise with immediate and 24 h postvalues of coagulation parameters in experienced athletes following a single, 42-km marathon run. DESIGN: Blood samples were taken 18 h before, immediately after, and 24 h after a marathon race from 14 well-trained individuals, and coagulation factors were measured. SETTING: The setting was a 42-km race on a cloudy day in May with an ambient temperature of 22 degrees C. SUBJECTS: The subjects were fourteen normal healthy individuals (12 men and 2 women) who regularly participated in runs of at least 20 km each week. INTERVENTION: The subjects all undertook a 42-km marathon run followed by a 24-h rest period and a repeat assessment. MAIN OUTCOME MEASURES: Coagulation factors including factor VIII (FVIII) and von Willebrand factor (vWF) were measured, as was the platelet response to aggregating agents. These responses are all considered as primary outcome measures of hypercoagulability and reflect the prethrombotic state. RESULTS: The hematocrit was not altered immediately after the race, but the platelet count (mean +/- SD) was significantly elevated (p < 0.05) to 322 +/- 54 x 10(9)/L from 256 +/- 70 x 10(9)/L, and the mean platelet size increased by 24 h (p < 0.05). Platelet aggregation in response to epinephrine, adenosine diphosphate, and collagen was decreased by 40%, 15%, and 60%, respectively, at 24 h; the response to ristocetin was only slightly (10%) altered. There was a significant elevation of beta-thromboglobulin in the plasma at the end of the race, and this elevation persisted for 24 h, indicating considerable release from the platelet alpha granules. The effect on platelet function was further demonstrated by a decrease in the quantity of glycoprotein Ib at 24 h, but not immediately after the race. There was an approximately 300% increase in the levels of FVIII, vWF antigen (vWF:Ag), and ristocetin cofactor activity. In addition, the normal vWF:Ag multimer pattern was changed in the samples taken immediately after the race. CONCLUSIONS: The data support the evidence of significant alteration of certain factors that are involved in coagulation following endurance exercise. Increases in FVIII and vWF are also noted in some prethrombotic conditions. The decreased platelet aggregation suggests early activation during the period of exercise.

Adult↗

Remote, mobile telemedicine: the satellite transmission of medical data from Mount Logan.

The purpose of this investigation was to demonstrate the potential of remote, mobile telemedicine during a four-week, high-altitude mountaineering expedition to Mount Logan, Canada's highest summit. Using a mobile satellite terminal and a laptop computer (both powered by a photovoltaic solar panel), ECG tracings and blood pressure measurements, in addition to colour images, short-segment video and audio clips were transmitted during the course of the ascent. The data were transmitted via a mobile communications satellite to a ground station in Ottawa, a distance of over 4000 km. The data were then transferred to the public switched data network and delivered to the University of Ottawa Heart Institute for analysis. Similarly, data were transmitted from the ground station to the expedition team on Mount Logan throughout the ascent. Using this technique, medical diagnosis and emergency care can be facilitated in extreme and isolated locations lacking a telecommunications infrastructure. Such technology has applications in developing countries, disaster response efforts, remote civilian and military operations, and in space operations.

Canada↗

The use of anabolic-androgenic steroids by Canadian students.

OBJECTIVE: To assess the prevalence of use of anabolic-androgenic steroids and other presumed performance-enhancing drugs and the associated knowledge, attitudes, and behavior of school-aged Canadians. DESIGN: A national survey was conducted using a self-report questionnaire distributed randomly to schools within each of five Canadian regions. SETTING: Canada. SUBJECTS: The subjects were 16,119 Canadian students, in the sixth grade and above, from 107 schools drawn randomly from five Canadian regions. MAIN OUTCOME MEASUREMENTS: The number of students reporting the use of anabolic-androgenic steroids and other performance-enhancing drugs in the year before the survey, the nature of such drug-taking activities, and the attitudes underlying the decision to take anabolic-androgenic steroids. RESULTS: More than 83,000 young Canadians (2.8% of the respondents) are estimated to have used anabolic-androgenic steroids in the year before the survey. Of those taking such drugs, 29.4% reported that they injected them; of the latter group, 29.2% reported sharing needles in the course of injecting anabolic-androgenic steroids. Significant numbers of respondents reported using other substances (caffeine, 27%; extra protein, 27%; alcohol, 8.6%; painkillers, 9%; stimulants, 3.1%; "doping methods," 2.3%; beta-blockers, 1%) in attempts to improve sport performance. CONCLUSIONS: The use of anabolic-androgenic steroids is more widespread than may have been assumed and is often accompanied by high-risk needle-sharing. Anabolic-androgenic steroid use is often intended to alter body build as opposed to accentuating sport performance. Many young Canadians use a variety of other substances in attempts to improve sport performance. Drug-taking of this kind represents a special challenge for educators, health professionals, and sport authorities.

Adolescent↗

Tobacco addiction and hypertension.

The significance of smoking in the hypertensive patient may be unappreciated. The risk of hypertension may be tripled in such patients. Tobacco addiction may also compromise the treatment of hypertensives. The importance of smoking cessation for hypertensive smokers cannot be overemphasized and should be seen as fundamental. Nicotine replacement therapy (NRT), when used appropriately, can enhance the likelihood of cessation. All smokers, but particularly hypertensive smokers, should be advised to quit and offered specific and ongoing assistance in this respect.

Humans↗