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Regulation of oxidative phosphorylation in intact mammalian heart in vivo.

A dynamic computer model of oxidative phosphorylation in intact heart was developed by modifying the model of oxidative phosphorylation in intact skeletal muscle published previously. Next, this model was used for theoretical studies on the regulation of oxidative phosphorylation in intact heart in vivo during transition between different work intensities. It is shown that neither a direct activation of ATP usage alone nor a direct activation of both ATP usage and substrate dehydrogenation, including the calcium-activated tricarboxylate acid cycle dehydrogenases, can account for the constancy of [ADP], [PCr], [P(i)] and [NADH] during a significant increase in oxygen consumption and ATP turnover encountered in intact heart in vivo. Only a direct activation of all oxidative phosphorylation complexes in parallel with a stimulation of ATP usage and substrate dehydrogenation enabled to reproduce the experimental data concerning the constancy of metabolite concentrations. The molecular background of the differences between heart and skeletal muscle in the kinetic behaviour of the oxidative phosphorylation system is also discussed.

Adenosine Triphosphate↗

Regular exercise attenuated lipid peroxidation in adolescents with Down's syndrome.

OBJECTIVES: This study was designed to ascertain whether regular exercise may attenuate lipid peroxidation in adolescents with Down's syndrome. MATERIALS AND METHODS: Thirty-one male adolescents with Down's syndrome performed a 12-week training program, 3 days/week at a work intensity of 60-75% of peak heart rate (HRmax=194.5-[0.56 age]). Plasmatic malondialdehyde (MDA) was determined by high performance liquid chromatography (HPLC). RESULTS: When compared to baseline, MDA content was decreased significantly. CONCLUSION: Regular exercise significantly decreased lipoperoxidation in Down's syndrome.

Adolescent↗

Dorsal and ventral streams: a framework for understanding aspects of the functional anatomy of language.

Despite intensive work on language-brain relations, and a fairly impressive accumulation of knowledge over the last several decades, there has been little progress in developing large-scale models of the functional anatomy of language that integrate neuropsychological, neuroimaging, and psycholinguistic data. Drawing on relatively recent developments in the cortical organization of vision, and on data from a variety of sources, we propose a new framework for understanding aspects of the functional anatomy of language which moves towards remedying this situation. The framework posits that early cortical stages of speech perception involve auditory fields in the superior temporal gyrus bilaterally (although asymmetrically). This cortical processing system then diverges into two broad processing streams, a ventral stream, which is involved in mapping sound onto meaning, and a dorsal stream, which is involved in mapping sound onto articulatory-based representations. The ventral stream projects ventro-laterally toward inferior posterior temporal cortex (posterior middle temporal gyrus) which serves as an interface between sound-based representations of speech in the superior temporal gyrus (again bilaterally) and widely distributed conceptual representations. The dorsal stream projects dorso-posteriorly involving a region in the posterior Sylvian fissure at the parietal-temporal boundary (area Spt), and ultimately projecting to frontal regions. This network provides a mechanism for the development and maintenance of "parity" between auditory and motor representations of speech. Although the proposed dorsal stream represents a very tight connection between processes involved in speech perception and speech production, it does not appear to be a critical component of the speech perception process under normal (ecologically natural) listening conditions, that is, when speech input is mapped onto a conceptual representation. We also propose some degree of bi-directionality in both the dorsal and ventral pathways. We discuss some recent empirical tests of this framework that utilize a range of methods. We also show how damage to different components of this framework can account for the major symptom clusters of the fluent aphasias, and discuss some recent evidence concerning how sentence-level processing might be integrated into the framework.

Aphasia↗

Use of electronic pagers to recall patients undergoing outpatient-based chemotherapy.

Long waiting times while receiving chemotherapy in an outpatient setting have been identified as contributing to patient dissatisfaction and discomfort by a number of authors. Following an observation of this practice in a non-medical establishment, and as part of our service improvement program, we introduced the use of message pagers to recall patients in our chemotherapy outpatient service. We audited the impact of this intervention by means of questionnaires directed at patients and nursing staff. Our audit found that this intervention was particularly popular with female patients. Perceived benefits included more freedom of movement, less boredom, and peace of mind at being contactable. There were no reported problems with pager operation. Nursing staff were keen promoters of the pagers to patients as they felt that their use gave them more control over work intensity and less disruption from patients enquiring about remaining "waiting time". We concluded that this intervention may benefit other outpatient chemotherapy services.

Ambulatory Care↗

Indexing method of digital audiovisual medical resources with semantic Web integration.

Digitalization of audiovisual resources and network capability offer many possibilities which are the subject of intensive work in scientific and industrial sectors. Indexing such resources is a major challenge. Recently, the Motion Pictures Expert Group (MPEG) has developed MPEG-7, a standard for describing multimedia content. The goal of this standard is to develop a rich set of standardized tools to enable efficient retrieval from digital archives or the filtering of audiovisual broadcasts on the Internet. How could this kind of technology be used in the medical context? In this paper, we propose a simpler indexing system, based on the Dublin Core standard and compliant to MPEG-7. We use MeSH and the UMLS to introduce conceptual navigation. We also present a video-platform which enables encoding and gives access to audiovisual resources in streaming mode.

Abstracting and Indexing↗

Multivariate approaches in plant science.

The objective of proteomics is to get an overview of the proteins expressed at a given point in time in a given tissue and to identify the connection to the biochemical status of that tissue. Therefore sample throughput and analysis time are important issues in proteomics. The concept of proteomics is to encircle the identity of proteins of interest. However, the overall relation between proteins must also be explained. Classical proteomics consist of separation and characterization, based on two-dimensional electrophoresis, trypsin digestion, mass spectrometry and database searching. Characterization includes labor intensive work in order to manage, handle and analyze data. The field of classical proteomics should therefore be extended to also include handling of large datasets in an objective way. The separation obtained by two-dimensional electrophoresis and mass spectrometry gives rise to huge amount of data. We present a multivariate approach to the handling of data in proteomics with the advantage that protein patterns can be spotted at an early stage and consequently the proteins selected for sequencing can be selected intelligently. These methods can also be applied to other data generating protein analysis methods like mass spectrometry and near infrared spectroscopy and examples of application to these techniques are also presented. Multivariate data analysis can unravel complicated data structures and may thereby relieve the characterization phase in classical proteomics. Traditionally statistical methods are not suitable for analysis of the huge amounts of data, where the number of variables exceed the number of objects. Multivariate data analysis, on the other hand, may uncover the hidden structures present in these data. This study takes its starting point in the field of classical proteomics and shows how multivariate data analysis can lead to faster ways of finding interesting proteins. Multivariate analysis has shown interesting results as a supplement to classical proteomics and added a new dimension to the field of proteomics.

Algorithms↗

Metadata and computer-based patient records.

"Metadata" is the fundamental set of items in the organization of health-care information, at least in computer-based patient records. Computer-based patient records remain controversial, and thus, to a considerable extent, the truth of all assertions about these areas remains a matter of opinion. A set of opinions generated during 5 years of exclusive and intense work is presented.

Humans↗

Stammering and therapy views of people who stammer.

UNLABELLED: This study used a postal questionnaire to seek the views of adults who stammer concerning the effect of stammering on their lives, the speech and language therapy and other remedies they have tried, and their hopes for speech and language therapy in the future. The 332 returned questionnaires indicated that stammering had the greatest adverse effect on school life and occupation. Speech and language therapy had been helpful to many, but the nature of the benefits and specific therapies used were not cited in many responses. An emergent theme in unhelpful therapy was the dissatisfaction that arises when individual needs are not met. In the future, people want help in controlling stammering and in developing coping strategies. The desire for timely and effective therapy for children, ongoing help and for group or intensive work has implications for service organization and therapist's skills. The survey highlights the need for therapists and clients to negotiate therapy aims and procedures that are clearly defined, appropriate to individual needs, achievable, and, if possible, recorded and measured. EDUCATIONAL OBJECTIVES: The reader will learn about and be able to list (1) the areas most and least affected by stammering, (2) the therapy approaches respondents had found helpful, and (3) other remedies that tried to help stammering.

Adolescent↗

Endoderm development: from patterning to organogenesis.

Although the ectoderm and mesoderm have been the focus of intensive work in the recent era of studies on the molecular control of vertebrate development, the endoderm has received less attention. Because signaling must occur between germ layers in order to achieve a properly organized body, our understanding of the coordinated development of all organs requires a more thorough consideration of the endoderm and its derivatives. This review focuses on present knowledge and perspectives concerning endoderm patterning and organogenesis. Some of the classical embryology of the endoderm is discussed and the progress and deficiencies in cellular and molecular studies are noted.

Animals↗

Effects of exercise on circulating vascular adhesion molecules in healthy men.

Based on previous studies showing an increase in circulating soluble intercellular adhesion molecule-1 (sICAM-1) after exercise, we hypothesized that exercise may also increase serum levels of the vascular cell adhesion molecule-1 (sVCAM-1) and sE-selection. In a prospective controlled clinical trial, serum levels of sE-selectin, sICAM-1 and sVAM-1 were measured before and after two different exercise protocols in healthy untrained men. Lactate levels increased up to 12.7 mmol/L (95% confidence interval: 10.1-15.9) and 3.6 mmol/L (CI: 2.4-4.7) after ergometry and after an one hour endurance exercise at 60% of the maximal work intensity, respectively (p = 0.028 vs baseline and controls). The maximal increase in lymphocyte counts of 106% (CI: 63-146), which was only of short duration, was higher immediately after ergometry as compared to that observed after endurance exercise (p = 0.028). However, the maximal increase in neutrophil counts of 178% (CI: 120-298) which was seen at 2 hours after endurance exercise was higher than that seen after ergometry (p = 0.028). In contrast, only small changes of circulating adhesion molecules were seen immediately after ergometry: sICAM-1 increased by 11% (CI: 4-25; p = 0.028), and similar tendencies were also observed for sVCAM-1 and sE-selectin. No other consistent and time-dependent changes of circulating adhesion molecules were observed and all differences and changes were < or = 11%. In sum our study provides evidence that recreational sporting activities in untrained healthy subjects at normal altitude have little influence on serum levels of the circulating vascular adhesion molecules sE-selectin, sVCAM-1 or sICAM-1.

Adult↗

[Market and ageing].

Ageing can be defined as growth of the proportion of elderly people in the population, but also as a group of transformations in life cycles: older age at time of first job, marriage, birth of first child, early retirement, longer life expectancy, active retirement, greater number of dependent persons. The economic impact of the ageing population has been extensively studied from the perspective of the social security fund. In France and in most developed countries, population ageing has considerably destabilized social accounting creating a gap between a system thought out after WWII and the present social environment. The current response of social security system to elderly person's needs is considered inadequate. There are however other consequences of ageing. It is important to measure the upheaval caused by longer life expectancy and changing life stages on all markets. Three kinds of markets are involved in different ways: job market, services market for the elderly and all goods market for seniors and golden aged. Many studies have focused on the links between economic production and physiological ageing. The traditional organisation of working conditions stresses working intensity over experience, young workers'capabilities over than those of older workers. The link between age and the job market can also be analyzed by considering supply and demand for employment for workers over 50. Another question is the workforce shortage forecasted in some sectors (health and social sectors in particular) and the role of immigration. Growth in the supply of long-term care will require restructuring of the sector's logistics and financing. Certain trends are appearing: government authorities are reducing their supply of services, private production is increasing, public financing is being maintained, and individual contributions are growing while the role of insurance has remained stagnant. A qualitative analysis of the markets also shows heterogeneous workers situations and status creating difficult consequences for management decision making. The best-known impact of ageing on markets is the development of the senior and golden-age markets (technical help, accessibility, improved housing, leisure activities and training...) The particularities of these markets and their development are extensively studied, particularly questions related to new technologies.

Age Factors↗

Effect of captopril, an angiotensin-converting enzyme inhibitor, in patients with angina pectoris and heart failure.

The effects of captopril and placebo were compared in 18 patients with chronic heart failure and angina pectoris with use of a double-blind crossover trial design. Symptoms were assessed by patient treatment preference, visual analogue scores and nitroglycerin consumption. Exercise performance was assessed using two different treadmill protocols of different work intensity with simultaneous measurement of oxygen consumption and by supine bicycle exercise and simultaneous radionuclide ventriculography. Arrhythmias were assessed by 48 h ambulatory electrocardiographic monitoring. Patients generally preferred placebo to captopril, and this appeared to be due to an increase in symptoms of angina with captopril. Treadmill exercise time on a high intensity protocol was shorter with captopril than with placebo; on a low intensity protocol, angina became a more frequent limiting symptom even though overall exercise performance was not changed. The heart rate-blood pressure product was reduced, but largely because of a reduction in blood pressure rather than in heart rate. During supine bicycle exercise, no differences in symptoms, exercise performance, ejection fraction or changes in blood pressure were noted and ventricular arrhythmias were reduced. Captopril does not appear to be clinically useful in alleviating angina pectoris in patients with heart failure, and this effect may be related to a decrease in coronary perfusion pressure. Nonetheless, desirable metabolic effects, a reduction in arrhythmias and potential effects on survival require further study of captopril in patients with both angina and heart failure.

Aged↗

Use of clinical data in predicting improvement in exercise capacity after cardiac rehabilitation.

Fifty-nine men with coronary heart disease underwent 1 year of supervised aerobic exercise. They performed exercise tests for maximal oxygen uptake, ST segment analysis, thallium scintigraphy and radionuclide ventriculography before and after the year of exercise. A computerized data base that included clinical descriptors and exercise test results was retrospectively reviewed to determine whether initial features could predict the patient's response to the exercise intervention. Poor correlations were found between the initial measurements and change in maximal oxygen consumption and other indexes of training effect. Patients who initially were in the poorest state of fitness showed the most improvement with training. None of the initial features from the history and physical examination, treadmill study or radionuclide studies was a good predictor of a beneficial result from the exercise program. The usual measurements of work intensity during training were poor predictors of outcome. A significant decrease in the amount of ischemia measured by thallium perfusion scintigraphy was demonstrated after training.

Adult↗

Exercise training improves functional status in patients with peripheral arterial disease.

PURPOSE: In patients with intermittent claudication (IC) a structured walking exercise program improves exercise performance. However, few studies have evaluated the effects of exercise training on functional status during daily activities. We hypothesized that a supervised exercise training program would improve functional status in patients with IC, with 24 weeks of training more beneficial than 12 weeks. A secondary aim was to evaluate the effects of strength training and combinations of strength and treadmill training on functional status. METHODS: Twenty-nine men with disabling IC were randomized to 12 weeks of either supervised treadmill training (3 hr/wk at a work intensity sufficient to produce claudication), strength training (3 hr/wk of resistive training of six muscle groups of each leg), or to a nonexercising control group. Functional status was assessed by questionnaires characterizing walking ability (Walking Impairment Questionnaire, WIQ), habitual physical activity level (Physical Activity Recall, PAR), and physical, social, and role functioning, well-being, and overall health (Medical Outcomes Study SF-20, MOS). Patients alos had their activity levels monitored with an activity monitor (Vitalog). RESULTS: After 12 weeks of treadmill training PAR scores increased by 48 metabolic equivalent hr/wk, the MOS physical functioning score by 24 percentage points, and the number of bouts of walking activity measured by the Vitalog by 4.5 bouts/hr (all p < 0.05). No changes were seen in WIQ scores. After 12 additional weeks of treadmill training improvements initially observed in the PAR, MOS, and Vitalog scores were maintained, and in addition the ability to walk distances (WIQ) improved by 31 percentage points, and the IC severity score had improved by 29 percentage points (both p < 0.05). After 12 weeks of strength training patients improved their WIQ walking speed, stair climbing scores, and MOS well-being scores with no other changes in functional status. Subjects in the control group did not improve functional status by any measure. Twelve weeks of treadmill training after the strength training program maintained WIQ walking speed scores, and activity level defined by Vitalog improved. Twelve weeks of combined treadmill and strength training after the control period had no effect on functional status. CONCLUSIONS: A supervised treadmill training program improved functional status during daily activities, with 24 weeks more effective than 12. In addition, treadmill training alone was more effective in improving functional status in patients with IC than strength training or combinations of the training modalities.

Aged↗

Nutrition and fuel utilization in the athletic horse.

Substrate depletion and end product accumulation are two important factors in exercise fatigue. Fatigue during long-term exercise results from a depletion of muscle and liver glycogen and coincides with an inability to maintain blood glucose levels. During high intensity exercise, the rapid catabolism of carbohydrate and the resultant production of lactate and hydrogen ions cause a reduction in muscle pH that inhibits maximum force generation. Dietary manipulations that can influence carbohydrate status or lactate accumulation may be beneficial to performance. In human athletes, carbohydrate loading and carbohydrate supplementation can enhance endurance time during long-term exercise. These practices have not been explored extensively in the equine athlete, although glycogen loading does not enhance the performance of horses during short-term intense work. Short-term work can be detrimentally affected if glycogen levels are inadequate. The most marked effect of exercise on nutrient requirements is in the energy requirement. Horses in heavy training may require more energy than they can consume on a conventional diet. Fat has been added to horse diets to increase energy density, usually at levels between 6% and 12% of the total diet. Although protein requirements may be slightly increased in the working horse, supplementing protein as a means of adding calories is not an efficient practice. In addition, although studies with horses are not available, human studies indicate that there are no benefits to vitamin supplementation above required levels. At this point, more is unknown than is known about feeding performance horses. Most information on fuel utilization is extrapolated from studies with rats and humans. Areas that have received little attention but are critical to optimizing feeding practices are the timing of pre-event feeding and the determination of ideal body composition in equine athletes of different types.

Animal Nutritional Physiological Phenomena↗

Gene therapy in heart disease.

Application of gene therapy to the field of cardiovascular disorders has been the subject of intensive work over the recent period. Gene therapy for cardiovascular disorders is now fast developing with most therapies being devoted to the consequences (ischemia) rather than the causes of atherosclerotic diseases. Recent human clinical trials have shown that injection of naked DNA encoding vascular endothelial growth factor promotes collateral vessel development in patients with critical limb ischemia or chronic myocardial ischemia. Promising studies in animals have also fueled enthusiasm for treatment of human restenosis by gene therapy, but clinical applications are warranted. Application of gene transfer to other cardiovascular diseases will require the coordinated development of a variety of new technologies, as well as a better definition of cellular and gene targets.

Genetic Therapy↗

Use of a wick to deliver preoperative mydriatics for cataract surgery.

Before cataract surgery at our institution, we traditionally dilated the pupils with 5 drops: proparacaine 0.5%, cyclopentolate 1%, phenylephrine 2.5%, flurbiprofen sodium 0.03% (Ocufen), and ofloxacin 0.3% (Ocuflox) at 15-minute intervals given 3 times. This was work intensive for the nursing staff. Since September 2000, we have used a wick soaked in a dilating mixture containing cyclopentolate 1%, phenylephrine 2.5%, diclofenac sodium 0.1% (Voltaren), and Ocuflox. Use of the wick has been beneficial and time saving to hospital staff.

Anti-Infective Agents↗

Vibrio cholerae O139 Bengal: odyssey of a fortuitous variant.

Vibrio cholerae O139, the new serogroup associated with epidemic cholera, came into being in the second half of the year 1992 in an explosive fashion and was responsible for several outbreaks in India and other neighbouring countries. This was an unprecedented event in the history of cholera and the genesis of the O139 serogroup was, at that time, thought to be the beginning of the next or the eighth pandemic of cholera. However, with the passage of time, the O1 serogroup of the El Tor biotype again reappeared and displaced the O139 serogroup on the Indian subcontinent, and there was a feeling among cholera workers that the appearance of this new serogroup may have been a one-time event. The resurgence of the O139 serogroup in September 1996 in Calcutta and the coexistence of both the O1 and O139 serogroups in much of the cholera endemic areas in India and elsewhere, suggested that the O139 serogroup has come to stay and is a permanent entity to contend with in the coming years. During the past 10 years, intensive work on all aspects of the O139 serogroup was carried out by cholera researchers around the world. The salient findings on this serogroup over the past 10 years pertinent to its prevalence, clinico-epidemiological features, virulence-associated genes, rapid screening and identification, molecular epidemiology, and vaccine developments have been highlighted.

Antigens, Bacterial↗