Assessment of the pharmacological effects of inotropic drugs on left ventricular pressure and contractility: an evaluation of the QA interval as an indirect indicator of cardiac inotropism.

INTRODUCTION: The ICH S7A and S7B guidelines require that effects of test substances on the cardiovascular system be assessed with respect to blood pressure, heart rate and electrocardiogram intervals. Where adverse effects are identified additional supplemental studies, including ventricular contractility, should be conducted as deemed appropriate. However, there is an absence of definitive guidance regarding when to pursue supplementary studies, in part due to ill-defined criteria of what constitutes an adverse effect and to surgical/technical monitoring limitations of study designs. However with advances in technology it is now feasible to develop models for assessing LVP and contractility in conjunction with standard assessments. The objectives of this study were to 1) develop a model for chronic evaluation of LVP and contractility, 2) illustrate changes in LV contractility without concurrent proportional changes in heart rate and/or systemic blood pressure and 3) determine if the QA interval, the time between the Q on the ECG and the beginning of the upstroke on the arterial blood pressure, can be used as a indicator of altered LV contractility. METHODS: Dogs (N=4) were implanted with a telemetry transmitter. LVP, contractility, ECG and BP were assessed prior to and up to 24 h following administration of Atenolol (10 mg/kg) and Pimobendan (0.45 mg/kg). RESULTS: Atenolol caused an approximately 30% decrease in HR, followed by a sustained decrease in maximum left ventricular contractility (+dP/dt mmHg/s). No effects were noted on blood pressure. Pimobendan caused a 100% increase in contractility (+dP/dt mmHg/s) which remained elevated for approximately 4 h. No effects were noted on blood pressure. Heart rate was highly variable initial decreasing, followed by a highly variable increase until 4 h postdose. Following administration of both compounds changes in maximum left ventricular contractility correlated with reverse changes in QA interval duration. DISCUSSION: This model demonstrates that evaluation of LV contractility complements measurements of heart rate and blood pressure as part of a more complete cardiovascular safety assessment strategy. Furthermore, we demonstrate an apparent correlation between dP/dt and QA interval and concluded that QA interval can be utilized as an indicator of a potential inotropic effect. However further confirmation should be assessed through additional in-vivo measurements of LVP and contractility.

A decrease in the association between the physical activity patterns of Australian parents and their children; 1985-1997.

The present study investigated the interactions between parents' and children's physical activity levels by examining whether or not parents who exercise have children who participate in sport. Of primary interest was an investigation of trends in these interactions over time. Information was collected from 10-13 y old children in 1985 (n = 2463) and then again in 1997-99 (n = 1469), about their sports participation and their perceptions of parents' exercise habits. Boys' participation in at least one sport declined from 87% in 1985 to 76% in 1997/1999 while, among girls, participation fell from 80% to 71%. According to their children's perceptions, mothers exercising regularly fell from 36% to 31% between surveys, while fathers exercising regularly fell from 39% to 32%. Interactions between parents' and children's exercise and sports behaviours were examined employing chi-square analysis techniques. Results showed gender-specific relationships for the 1985 sample, such that active fathers were associated with increased participation in sports by boys, and inactive mothers were associated with less participation in sports by girls. These interactions seemed to diminish over time. It is possible that changes in social structures during this time may be affecting familial behaviour relationships, such as the role modelling of active behaviours.

Client-centred assessment and the identification of meaningful treatment goals for individuals with a spinal cord injury.

STUDY DESIGN: Retrospective analysis. OBJECTIVES: (1) Describe the self-care, productivity and leisure problems identified by individuals with a spinal cord injury (SCI) during rehabilitation, (2) describe the perceived level of satisfaction and performance with self-care, productivity and leisure activities following an SCI, (3) quantify the relationship between the Canadian occupational performance measure (COPM), a client-centred, individualized measure of function, and the functional independence measure (FIM). SETTING: Tertiary rehabilitation centre, spinal cord injury unit, GF Strong Rehabilitation Centre, Vancouver, Canada. METHODS: Health records from 41 individuals with an SCI admitted between 2000 and 2002 were reviewed. Information was obtained from assessments performed on admission and discharge. Self-care, productivity and leisure problems identified by individuals with an SCI were described and their perceived level of performance and satisfaction was calculated. The relationship between the COPM and the FIM was measured by the Pearson product correlation. RESULTS: Self-care goals were identified most frequently (79%) followed by productivity (12%) and leisure (9%) goals. The top three problems identified by individuals with an SCI were functional mobility (including transfers and wheelchair use), dressing and grooming. A fair relationship was found between the COPM and the FIM (r between 0.351 and 0.514, P<0.05). CONCLUSIONS: The results highlight the importance of including a client-centred outcome measure in the assessment of individuals with an SCI. Initial support is provided for use of the COPM in individuals with an SCI.

Morphological evolution of athletes over the 20th century: causes and consequences.

Over the course of the past century it has become increasingly difficult to find athletes of the size and shape required to compete successfully at the highest level. Sport is Darwinian in that only the 'fittest' reach the highest level of participation. Not every physical characteristic could be expected to play a role in this selection process, but two that are important and for which substantial data assemblies exist, are height and mass. Measurements of elite athlete sizes were obtained from a variety of sources as far back as records allowed. We charted the shift in these anthropometric characteristics of elite sportspeople over time, against a backdrop of secular changes in the general population. Athletes in many sports have been getting taller and more massive over time; the rates of rise outstripping those of the secular trend. In open-ended sports, more massive players have an advantage. Larger players average longer careers and obtain greater financial rewards. In some sports it is equally difficult to find athletes small enough to compete. In contrast, there are sports that demand a narrow range of morphological characteristics. In these sports the size of the most successful athletes over the century has remained constant, despite the drift in the population characteristics from which they are drawn. A number of social factors both drive and are driven by the search for athletes of increasingly rare morphology. These include globalisation and international recruitment, greater financial and social incentives, and the use of special training methods and artificial growth stimuli. In many sports the demand for a specific range in body size reinforces the need to adopt questionable and illegal behaviours to reach the required size and shape to compete at the top level. Future scenarios also include 'gene-farming' through assortative mating and athlete gamete banks.

The 'price' of Olympic Gold.

In 1981 the Commonwealth Government established the Australian Institute of Sport (AIS). The Australian Sports Commission (ASC) which administers the AIS has 2 objectives: (1) excellence in sports performances; and (2) increased participation in sports and sports activities. State-based institutes of sport have also been established with the same or very similar objectives. Federal policy directs the bulk of the ASC budget to elite athlete programs. A smaller proportion goes towards community participation. The official reason is based on the notion of the 'trickle-down' or 'demonstration' effect. That is, a flow-on of benefits to the broader community in the form of increased participation as a direct result of elite sports success. The aims of this study were to determine the (1) spending pattern to elite sports programs for the 5 Olympics 1976/77 to 1995/96, (2) evidence for the two ASC objectives having been met, and (3) expected medal tally at the 2000 Olympic Games. Results show funding (in 1998 dollars), has accelerated from about $1.2 million (1976/77) to $106 million in (1997/98), particularly since the Games were awarded to Sydney. The total amount spent on elite athletes was $0.918 billion. In the period 1980-96 Australia won 25 gold and 115 total Olympic medals. This equates to approximately $37 million per gold and $8 million per medal in general. There was a significant linear relationship between money spent and total medals won. This was also found when all medal types were analysed independently. The predicted medal tally in 2000 (based on the cost per medal and the expenditure towards Sydney) indicates the medal count will be about 14+/-1 gold, 15+/-2 silver and 33+/-4 bronze. Based on our nation's record of international sporting achievement, there is little doubt we have fulfilled the ASC's first objective. Current data on physical activity patterns of Australians suggest the second objective has not been met. Focusing attention on and achieving the first objective does not appear to have any bearing on the second objective. It is time to revisit the notion that elite sporting success leads to greater mass participation as a result of the so-called 'trickle-down' effect.

Increasing condom use among adolescents with coalition-based social marketing.

OBJECTIVES: This study evaluated a multimodal social marketing intervention to reduce the sexual transmission of HIV infection among adolescents in Sacramento, California, USA. DESIGN: Five rounds of a cross-sectional random sample telephone survey were conducted from December 1996 to October 1998. The total number of respondents was 1402. RESULTS: A statistically significant, increasing trend in exposure to the intervention was detected. The number of channels through which an adolescent had been exposed to the intervention was associated with condom use at last sex with main partner [odds ratio (OR) 1.26, P < 0.01] and with psychosocial determinants of this behavior. After statistical adjustments for sex, age, and race/ethnicity to make the survey rounds comparable, the proportion of adolescents who had used a condom at last sex increased 4.3 percentage points over the 1 year intervention period. CONCLUSION: Social marketing can be combined with behavioral science to reduce the risk of HIV infection and other sexually transmitted diseases (STD) among adolescents in a large geographical area. Such a reduction can exceed expectations based on national secular trends.

Applying the Sports Medicine Australia pre-exercise screening procedures: who will be excluded?

Recently Sports Medicine Australia (SMA) and the Australian Association for Exercise and Sport Science (AAESS) developed guidelines for pre-exercise screening and supervision of fitness testing, based on the American College of Sports Medicine (ACSM) system. The procedure involves classifying individuals into one of three risk groups (apparently healthy, at higher risk, with known disease). Using data collected in a 1992 survey of 2298 Australian adults aged 18-78 years conducted by the Department of the Arts, Sport, the Environment and Territories (DASET), we calculated the percentage of the general population falling within each risk group and therefore exclusion rates (ie the proportion of subjects who, it is recommended, would require medical clearance prior to exercise or exercise testing). The analysis of data found that between 43-73% of males and 44-61% of females would require clearance. A cost analysis suggests that a rigorous application of the SMA-AAESS guidelines would cost between $250 million and $1.2 billion each year. On the basis of the results, suggestions for reviewing the guidelines have been proposed.

Collecting data on potentially harmful events: a method for monitoring incidents in general practice.

OBJECTIVE: The prediction and subsequent prevention of errors, which are an integral element of human behaviour, require an understanding of their cause. The incident monitoring technique was developed in the study of aviation errors in the Second World War and has been applied more recently in the field of anaesthetics. This pilot study represents one of the first attempts to apply the incident monitoring technique in the general practice environment. METHOD: A total of 297 GPs across Australia anonymously reported details of unintended events which harmed or could have harmed the patient. Reports were contemporaneously recorded on prepared forms which allowed a free text description of the incident, and structured responses for contributing and mitigating factors, immediate and long-term out-comes, additional costs etc. RESULTS AND DISCUSSION: The first 500 reports were analysed using both of qualitative and quantitative methods and a brief overview of results is presented. The methodological issues arising in the application of this technique to such a large, widely spread profession, in which episodes of care are not necessarily confined to a single consultation, are discussed. This study demonstrated that the incident monitoring technique can be successfully applied in general practice and that the resulting information can facilitate the identification of common factors contributing to such events and allow the development of preventive interventions.

Tests and investigations. Indicators for better utilisation.

Diagnostic tests and investigations are standard tools for today's general practitioner. However, without reliable systems for the management of tests and test results, these valuable assets may become a liability to the GP, with the possibility of unforeseen adverse events arising at several points in the total investigative process. Exploring GPs' reports of such incidents may provide opportunities for improvements in patient care.

Addressing racism in psychiatry: is the therapeutic community model applicable?

Several reports have documented the failure of statutory psychiatric services in Britain to provide for the needs of clients from minority ethnic groups. Black clients are particularly underrepresented in Psychotherapy for reasons which are complex and varied, but include the institutionalised racism which pervades British society. We argue that the Therapeutic Community (TC) model of treatment (or aspects of it deployed in other mental health situations) provides a potential for a less racist service. Using the Henderson Hospital TC as a case in point, we argue that the TC is an approach which can meet the needs of black peoples. However, it is acknowledged that despite the ideological suitability of the TC model for black clients, in practice the Henderson Hospital is not fulfilling its role in providing therapy to this group. We discuss possible explanations and suggest the practical changes necessary, so that Henderson Hospital can meet the needs of clients in a multi-cultural Britain.

Fluorescence assessment of skin perfusion after oral fluorescein.

This study evaluated oral ingestion as the route of fluorescein administration for fluorescence assessment of skin perfusion. In 10 anesthetized rats, dorsal pedicle flaps were raised to produce graded perfusion; then fluorescein (7.5 mg/kg) was administered via an oropharyngeal tube. Quantification of skin fluorescence, performed with the fiberoptic fluorometer 45 minutes after dye ingestion, delineated a significant difference between the perfusion of flap regions that remained viable and those that subsequently became dystrophic (p less than 0.05). The precision was equivalent to that previously reported after intravenous dye. In addition, the gradual delivery of dye after oral administration permitted monitoring of slope of uptake and time to peak. Each of these pharmacokinetic parameters delineated a significant difference between viable and nonviable sections. As measures of relative change in fluorescence, they are independent of skin color and thickness. This feature suggests that the oral route actually may improve the accuracy and reliability of the fluorescein test.

Comparative assessment of blood flow to canine island flaps.

Fluorometric quantification of dye delivery, laser Doppler flowmetry, and transcutaneous measurement of tissue oxygen level were evaluated in canine island flaps subjected to vascular occlusion. Each technique readily identified the clamping insult. Relative fluorescein delivery to the flap (compared with a reference area) decreased from 66% before clamping to almost zero during clamping. Laser Doppler readings rapidly declined from an average of 230 to an average of 31 mV. Oxygen readings rapidly declined from 57 to 1 mm Hg. Laser Doppler flowmetry and transcutaneous oxygen monitoring seem best suited for continuous monitoring of trends at a single site. Fluorometry is more precise and can be used to monitor multiple sites. One should weigh the benefits of this technique against the need for dye injection.

Assessment of delay in bilateral thoracoabdominal island flaps in the rat.

This study demonstrates improved perfusion and viability following surgical delay in a bilateral paired flap model that minimizes the effects of systemic variables in the rat. Surgical delay was achieved in one of two paired thoracoabdominal island flaps by ligating and cutting the inferior epigastric (distal) pedicle three days before flap construction. This created a hypoperfused zone. Within three days of delay, perfusion of the delayed region, as documented by quantification of tissue fluorescein delivery, increased markedly and often exceeded nondelayed values. Construction of 2 X 11-cm island flaps based on the superior epigastric pedicle at this time was associated with an average of 1.1-cm necrosis, compared with 2.6 cm in nondelayed flaps.