Strategic steps for advanced molecular imaging with magnetic resonance-based diagnostic modalities.

With the rapidly-expanding sophistication in our understanding of cancer cell biology, molecular imaging offers a critical bridge to oncology. Molecular imaging through magnetic resonance spectroscopy (MRS) can provide information about many metabolites at the same time. Since MRS entails no ionizing radiation, repeated monitoring, including screening can be performed. However, MRS via the fast Fourier transform (FFT) has poor resolution and signal-to-noise ratio (SNR). Moreover, subjective and non-unique (ambiguous) fittings of FFT spectra cannot provide reliable quantification of clinical usefulness. In sharp contrast, objective and unique (unambiguous) signal processing by the fast Padé transform (FPT) can increase resolution and retrieve the true quantitative metabolic information. To illustrate, we apply the FPT to in vitro MRS data as encoded from malignant ovarian cyst fluid and perform detailed analysis. This problem area is particularly in need of timely diagnostics by more advanced modalities, such as high-resolution MRS, since conventional methods usually detect ovarian cancers at late stages with poor prognosis, whereas at an early stage the prognosis is excellent. The reliability and robustness of the FPT is assessed for time signals contaminated with varying noise levels. In the presence of higher background noise, all physical metabolites were unequivocally identified and their concentrations precisely extracted, using small fractions of the total signal length. Via the "signal-noise separation" concept alongside the "stability test", all non-physical information was binned, such that fully denoised spectra were generated. These results imply that a reformulation of data acquisition is needed, as guided by the FPT in MRS, since a small number of short transient time signals can provide high resolution and good SNR. This would enhance the diagnostic accuracy of MRS and shorten examination times, thereby improving efficiency and cost-effectiveness of this high throughput cancer diagnostic modality. Such advantages could be particularly important for more effective ovarian cancer detection, as well as more broadly for improved diagnostics and treatment within oncology.

Cardiovascular evaluation of the worker and workplace: a practical guide for clinicians.

Unlike several other branches of medicine (e.g., pulmonology), primary cardiology has yet to fully develop a discipline of occupational cardiology. The authors outline an approach for including a focused occupational history in the CV work-up and present a graded, risk-stratified algorithm for occupational cardiologic assessment. This work-up can help clinicians make specific recommendations concerning working conditions, as these impact upon the patient's CV status.

The workplace and cardiovascular health: conclusions and thoughts for a future agenda.

The evidence in this book provides convergent validation of a causal relationship between workplace stressors and CVD. Here, the editors explore new strategies for enhanced prevention and clinical management, work place interventions, and social policy to reduce the impact of CVD. These strategies acquire an urgent public health dimension, given the magnitude of the CVD epidemic and the current deterioration in conditions of working life.

Why the workplace and cardiovascular disease?

Cardiovascular disease (CVD) remains the major cause of morbidity and mortality in the industrialized world. Current approaches to managing the CVD epidemic are based on powerful engineering models and advanced medical techniques. Innovative research has identified a number of risk factors for hypertension and CVD. However, our understanding of these disorders and our ability to manage the epidemic remain limited. A social epidemiologic paradigm suggests that essential hypertension and CVD are diseases of industrialized society of rather recent historical origins. To better understand and manage the CVD epidemic, current models need to incorporate a heretofore relatively neglected realm of social life in the workplace.

What prevents professional drivers from following physicians' cardiologic advice?

BACKGROUND: There is a scarcity of published studies of the effects of cardiac counselling among professional drivers (PD). Aims of the study were: (1) to examine explanatory variables for two classical 'driver' risk factors - body mass index (BMI), and smoking - and to analyse the interrelations among smoking cessation, losing weight and work-related life changes; (2) to assess the effectiveness of risk factor counselling after 6 months, and (3) to gain insight into possible discrepancies between PD perception of needed changes and compliance with the physician's advice. METHODS: There were 4 groups of male PD: 13 with ischemic heart disease, 12 hypertensives, 10 borderline hypertensives and 34 normotensives. Baseline cardiovascular risk factors as well as occupational and behavioral data were assessed via questionnaire. The counselling was aimed at smoking cessation, weight loss and promoting leisure-time physical activity. Qualitative methods were used to assess PD perceptions about the work environment and health promotion. RESULTS: Baseline smoking intensity was best predicted by the total burden of occupational stress and number of smoking years. Baseline BMI was best predicted by long work hours behind the wheel, low availability of attachment outside work and low self-reported job strain. Self-initiated smoking cessation was best predicted by few smoking years, low coffee intake and admitting fear during driving. Physical activity was significantly increased after 6 months. Losing weight was associated with: quitting or diminishing smoking and making other, work-related, life changes. None of the heavy smokers decreased their daily number of cigarettes after 6 months, although expressing the need to do so in self-generated statements. CONCLUSIONS: Exposure to occupational stressors, mainly, long work hours and the concomitant denial of job strain, in combination with low availability of social attachment outside work, could contribute to maintenance of maladaptive behavior in PD. These findings could serve as a basis for designing standardized intervention trials and suggest that modification of the work environment, with participation of the drivers, is a needed component of such trials. Particular attention should be paid to the length and scheduling of work shifts.

Occupational profile and cardiac risk: possible mechanisms and implications for professional drivers.

There has been at least forty empirical investigations concerning cardiovascular disease (CVD) among professional drivers (PDs). Standard cardiac risk factor status does not consistently distinguish PDs from other lower risk groups. PDs showed more than twice the overall exposure to stressful work factors compared to referents. They also showed lower maximum bicycle exercise level with a higher double product and higher diastolic blood pressure at the end of exercise compared to controls. Catecholamine excretion has been reported to be elevated during driving. Ambulatory measurements showed higher systolic and diastolic blood pressure in drivers before, during and after driving shifts. Using spectral analysis, the low to high frequency ratio was more than doubled towards the end of a 4-hour drive compared to the early one and a linear increase in 0.1 heart rate variability as a function of distance driven. Reactivity to headlight glare has been shown to roughly parallel the degree of CVD severity in PDs with IHD, essential and borderline hypertension. It was postulated that PDs with IHD form a powerful association between the exposure to glare and the stressfulness of driving and this association was resistant to extinction. The occupational medicine specialist "should have the authority to check the patient regularly in the workplace itself (to ascertain whether or not) the decision to return to work is still valid". An integrated diagnostic approach for PDs might entail using exercise stress testing, with evaluation of silent myocardial ischaemia and heart rate variability during work as well as laboratory tests which simulate aspects of their work environment, with catecholamines measured in relation to these procedures. Assessment of left ventricular mass and further evaluation of atherogenic biochemical abnormalities would be of value for further untangling the mechanisms of cardiac risk among PDs.

Psychophysiologic sensitization to headlight glare among professional drivers with and without cardiovascular disease.

Previous studies have shown that young, healthy professional drivers show heightened central nervous system arousal and cardiovascular hyperreactivity to simulated headlight glare. Electroencephalographic and cardiovascular response and recovery to simulated headlight glare (the glare pressor test) were examined in 4 groups of male professional drivers (age 25-52 years)--12 with ischemic heart disease (IHD), 12 with hypertension (HTN), 10 with borderline hypertension (BHTN), and 34 who were healthy--and in 23 non-professional driver controls--with the aim of assessing sensitization to this night driving stressor in relation to degree of cardiovascular disease severity. After glare exposure the IHD drivers showed the most pronounced alpha blockade, a rise in diastolic blood pressure (DBP; p < .05), and, unlike the other groups, a persistent fall in finger pulse volume (p < .02). The BHTN group reacted initially with DBP rise and finger pulse drop (ps < .05 and .02, respectively), mainly without central nervous system arousal. The DBP remained constant in normotensive professional drivers older than 40. The drivers' cardiovascular responses to glare were inversely related to reported stressors and subjective experience. Anxiety trait and long work hours were associated with heightened central arousal to glare in professional drivers. The results suggest that there may be progressive degrees of sensitization to glare exposure in these samples, with the least among normotensive professional drivers older than 40, moderate levels in borderline hypertensives, and the most severe in drivers with IHD.

Cardiovascular dysfunction related to threat, avoidance, and vigilant work: application of event-related potential and critique.

An integrative approach is suggested to track symbolically simulated work environment stressors, as an act to burden higher cortical function in the exposed groups. ERP would be made together with measurement of end organ stress responses as well as measurements of perceived conditions. Field studies would be the necessary complement. The following conclusions are culled from the reviewed literature: among the pilots, cardiovascular problems are the most important cause of loss of licence in Europe and North America. Interactions with coworkers for air traffic controllers have been associated with cardiovascular disability. Comparing various degrees of heart disease severity among professional drivers, the IHD drivers showed the smallest N2 amplitudes and the greatest diastolic blood pressure reactivity. P300 target amplitude showed an inverse correlation with number of work hours behind the wheel. The IHD drivers were envisioned in a phase of disturbance of the selective attentional process. An interrelation has been found between Event-Related Slow Potential ERSP and midinterval heart rate acceleration associated with displeasure and arousal. A positive correlation has been found between the amplitude of the ERSP and ventricular arrhythmia rate in cardiac patients. Lowering of arrhythmia rate in response to antiarrhythmic agents was associated with a significant attenuation of the ERSP. Either acceleration or deceleration is associated with the appearance of the late CNV to the aversive noise burst. There might be a "common generator behind both anticipatory heart rate responses and cortical events." CNV might be related to frontally mediated stress mechanisms.

Lipoprotein(a) as a determinant of coronary heart disease in young women.

BACKGROUND: Lipoprotein(a) [Lp(a)] appears to be a risk factor for coronary heart disease (CHD) in men. The role of Lp(a) in women, however, is less clear. METHODS AND RESULTS: We examined the ability of Lp(a) to predict CHD in a population-based case-control study of women 65 years of age or younger who lived in the greater Stockholm area. Subjects were all patients hospitalized for an acute CHD event between February 1991 and February 1994. Control subjects were randomly selected from the city census and were matched to patients by age and catchment area. Lp(a) was measured 3 months after hospitalization by use of an immunoturbidometric method (Incstar) calibrated to the Northwest Lipid Research Laboratories (coefficient of variation was < 9%). Of the 292 consecutive patients, 110 (37%) were hospitalized for an acute myocardial infarction, and 182 were hospitalized (63%) for angina pectoris. The mean age for both patients and control subjects was 56 +/- 7 years. Of participants, 74 patients (25%) and 84 control subjects (29%) were premenopausal. The distributions of Lp(a) were highly skewed in both patients and control subjects, with a range from 0.001 to 1.14 g/L. Age-adjusted odds ratio for CHD in the highest versus the lowest quartile of Lp(a) was 2.3 (95% confidence interval [CI], 1.4 to 3.7). After adjustment for age, smoking, education, body mass index, systolic blood pressure, total cholesterol, triglycerides, and HDL, the odds ratio was 2.9 (95% CI, 1.6 to 5.0). The odds ratios were similar when myocardial infarction and angina patients were compared with their respective control subjects. The odds ratios were 5.1 (95% CI, 1.4 to 18.4) and 2.4 (95% CI, 1.3 to 4.5) in premenopausal and postmenopausal women, respectively. CONCLUSIONS: These results suggest that Lp(a) is a determinant of CHD in both premenopausal and postmenopausal women.

Exercise testing of young, apparently healthy professional drivers.

OBJECTIVES: The purpose of this study was to examine the responses of young, apparently healthy professional drivers to exercise testing. METHODS: A bicycle exercise test was performed by a randomly selected group of 42 apparently healthy, male professional drivers aged 20 to 40 years and a group of 30 building workers, who formed a reference group. RESULTS: The mean maximal exercise level was significantly lower for the drivers [139 (SD 32) W] than for the referents [155 (SD 31) W] (P < 0.05). The mean systolic blood pressure and heart rate did not differ significantly between the groups at the end of the exercise, but the mean double product was significantly higher for the drivers. The mean diastolic blood pressure at the end of the exercise was 97 (SD 14) mm Hg [12.9 (SD 11.9) kPa] for the drivers and 79 (SD 19) [10.5 (SD 2.5) kPa] for the referents (P < 0.01). The exercise was stopped due to diastolic hypertensive reactions [diastolic blood pressure > 115 mm Hg (> 15.3 kPa)] in 13 (31%) of the drivers and 3 (10%) of the referents (P < 0.05). Eight of the thirteen drivers with a hypertensive reaction had three or more cardiac risk factors. CONCLUSIONS: There seems to be a high occurrence of diastolic hypertensive reactions to exercise among professional drivers. These reactions may be associated with risk of ischemic heart disease and hypertension. Further exercise testing of professional drivers is warranted. More sensitive methods may be indicated in selected cases, since the cardiovascular status of this cohort is a vital concern with respect to traffic safety.

Electrocortical responses to ecologically relevant visual stimuli among professional drivers with and without cardiovascular disease.

Electrocortical responses were assessed using two simulated aspects of visual signals encountered in traffic: the Glare Pressor Test (GPT) and Event-Related Potential Avoidance Task (ERPAT) among four groups of male professional drivers: 12 with ischemic heart disease (IHD), 12 hypertensives, 10 borderline hypertensives, 34 who were apparently healthy and 23 nonprofessional driver healthy control subjects. The blood pressure (BP) responses immediately after the ERPAT were also measured. There was a significant between groups effect for the amplitude of the target N2 component in the ERPAT (p = 0.02), with the lowest means among the drivers with IHD and the highest among those with hypertension. Drivers with IHD also showed the highest diastolic BP reactivity to the ERPAT. Significantly more than the expected number of drivers with IHD failed to recover alpha activity after the first glare impulse of the GPT. Professional drivers who failed to recover baseline levels of alpha activity after the GPT showed a significantly smaller N2 amplitude compared to those who recovered (p = 0.01). There was a positive correlation between abundance of alpha activity at rest with P300 amplitude (p = 0.02). An inverse relation was found between number of work hours behind the wheel and the amplitude of the target P300 (p = 0.04). Results are interpreted in light of recent advances concerning integrative mechanisms of defence versus vigilance response patterns. The findings in this study justify further applications of these psychophysiologic methods to assess the relationship between simulated signals of the work environment and mechanisms of cardiac risk in this occupational group.

Mechanisms of cardiac risk among professional drivers.

This literature review indicates that professional drivers have excess cardiac risk that is not fully explained by standard risk factors. The contribution of occupation is suggested by two independent methods and by psychophysiological studies during on the job driving. Driving has been conceptualized as a threat-avoidance task. Stimuli encountered in traffic are not inherently aversive but become so by association with driving experience, a formulation corroborated by laboratory studies in which stimuli such as car headlights elicit cardiovascular hyperreactivity and electroencephalographic signs of arousal in professional drivers. More-advanced neurophysiological methods (event-related potentials) show higher cortical electronegativity to imperative signals among professional drivers than among non-driver referents. These data are viewed in light of reports of possible associations between event-related slow potentials and cardiac risk. A clinically and ecologically relevant neurocardiological model is proposed, and preventive strategies, including workplace interventions, are suggested.

Assessment of long-term stability of chronic ventricular pacing thresholds in steroid-eluting electrodes.

Sixteen patients with Medtronic 4003 steroid-eluting electrodes implanted in the ventricular position were followed over 5 years. In each patient a special type of Medtronic 2443 pacemaker was implanted to allow programming of output at 1.35 V. Chronic threshold values in these patients measured at an output of 1.35 V were stable over the first 18 months of follow-up. Mean values were: 0.06 +/- 0.03 msec at 6 months and 0.08 +/- 0.02 msec at 18 months; these did not differ from each other significantly. However, during the period from 18 to 36 months postimplantation, a significant increase in mean pacing threshold was observed: 0.08 +/- 0.02 msec at 18 months postimplantation versus 0.14 +/- 0.05 msec at 36 months (P < 0.01). After 36 months, the chronic pacing threshold remained stable until the end of the 5-year follow-up period. Further long-term study of chronic threshold behavior of steroid-eluting electrodes measured at low amplitudes is warranted.