Is high titre ANA specific for connective tissue disease?

OBJECTIVE: A positive antinuclear antibody (ANA), while sensitive, is not specific for systemic lupus erythematosus or connective tissue diseases (CTD). The purpose of the present study was to review those sera with a high titre (> or = dilutions above screening) ANA and determine from a review of the charts if these higher titres offered a satisfactory specificity for CTD. METHODS: All FANA testing in this region is carried out in one of two related laboratories. We reviewed the medical records of patients who had a positive ANA at a titre 4 dilutions above screening at this city-wide laboratory over a 6-month period to determine whether this titre ("high titre") may offer relative diagnostic certainty. Antibodies to extractable nuclear antigens (ENA) and native DNA were also obtained. RESULTS: 422 ANA results were positive at high titre. The medical record was available for review in 320 patients, of whom 238 (75%) were seen by a specialist physician, almost always including a rheumatologist. Our review determined that 35% had a diagnosis of connective tissue disease, 21% had a diagnosis of a possible/probable inflammatory disease, 16% had an alternative specific diagnosis provided, and in 29% no final disease specific diagnosis was recorded but CTD was not suggested to us or the specialist by the data available. One or more anti-ENA antibodies and/or anti-DNA were positive in 69 (22%) and 8% of the sera tested respectively. CONCLUSION: While long term follow-up is still required, a significant proportion of patients with high titre ANA have no CTD at the time of testing. Setting a higher cutoff for reporting of ANA may not increase specificity sufficiently to make it a useful alternative or addition to reporting a positive or negative value at screening titre alone.

Designing attenuators for total-body irradiation using virtual simulation.

In total-body photon irradiation, the lungs are the most commonly shielded organ. Lung compensators are often designed by using high-energy portal films. Other organs, such as the kidneys and liver, are poorly visualized in portal films due to their unit-density composition. A computed tomography-based technique to design kidney and liver attenuators involves outlining these organs in a virtual simulation. The position and the shape of the attenuator are then determined from a digitally-reconstructed radiograph. Appropriate attenuator thickness is determined from measured transmission curves. This article provides a summary of this technique for total-body photon irradiation in a 4-MV photon beam.

Assessment of health locus of control in the use of nonconventional remedies by patients with rheumatic diseases.

OBJECTIVE: To assess the prevalence and characteristics of the use of nonconventional remedies (NCR) and to determine the type of health locus of control that the users of NCR may have. METHODS: We conducted a cross sectional survey of 200 patients with rheumatic diseases at 3 outpatient rheumatic clinics in Edmonton, Canada. A face-to-face structured interview was administered by a trained assistant to evaluate the prevalence of use, and patient beliefs, perceptions, and expectations in relation to NCR. To assess locus of control the Multidimensional Health Locus of Control (MHLC) instrument was applied. RESULTS: One-hundred nineteen patients (60%) had used a total of 530 NCR (range 1-25) in the previous 12 months; 94 (79%) of these patients used 309 NCR (mean of 3, range 1-15 remedies). Forty-seven percent had received at least one NCR before the first rheumatology consultation, but an additional 8% initiated NCR after their initial contact with a rheumatologist at our clinics. Only 22 (18%) of the patients using NCR notified their rheumatologist about their use. The mean reported expenditures for the users of NCR in the past 12 months were $260.00 CDN per patient (range 0 to $3,520), and the mean reported expenditures for the ever users of NCR were $730.00 CDN (range 0 to $9,720). Patients who used NCR in the past 12 months were younger (52 +/- 14 vs 58 +/- 15 yrs; p = 0.003), slightly more disabled (1.26 vs 1.11, modified Health Assessment Questionnaire; p = 0.006), and in the middle income class (p < 0.001). Possible associations between MHLC and the use of NCR were assessed in different ways in the logistic regression models, including the entry of MHLC subscales as means or class intervals, and NCR as users versus no users, or as higher users (> 4 NCR) versus no users of NCR. The use of NCR, ever or in the past 12 months, did not have statistical association with any of the subscales of the MHLC. CONCLUSION: In this survey over one-half of patients used NCR for treatment of their rheumatic disease. NCR were costly and the MHLC scales scores alone did not explain all the variance in health behaviors. Other contributing factors such as perceived severity of the disease, health motivation, or previous behavior should be addressed in further research.

Hemodynamic and hormonal changes during pneumoperitoneum and trendelenburg positioning for operative gynecologic laparoscopy surgery.

Objective: The number and types of surgical procedures being preformed using laparoscopic technique is increasing due to technological advances. Recent studies suggest the carbon dioxide pneumoperitoneum and patient positioning causes hemodynamic alterations, respiratory acidosis, and a release of stress hormones. However, to date, no studies have investigated the physiological effect of laparoscopic procedures lasting more than 60 minutes on the stress response and the effect of Trendelenburg positioning. The purpose of this study was to identify the physiological effect of pneumoperitoneum and positioning during prolonged laparoscopy on hemodynamic (cardiac index, mean arterial pressure, heart rate, systemic vascular resistance, and stroke volume), metabolic (arterial blood gases), and hormone (arginine vasopressin, aldosterone, and plasma renin activity) parameters. We hypothesized that pneumoperitoneum and patient positioning will alter the hemodynamic, hormone, and metabolic parameters.Methods: The study was longitudinal in design and sampled a total of 31 healthy subjects having a gynecologic oncologic laparoscopic procedure at Hurley Medical Center, Flint, Michigan. The subjects were randomly assigned one of three groups receiving an initial insufflation pressure of either 10, 15, or 18 mmHg. After obtaining informed consent hemodynamic, metabolic, and hormone measurements were obtained at the following times: 1) pre-induction, 2) post-induction, 3) post-insufflation, 4) post-Trendelenburg 5 minutes and at 30, 60, 90, and 120 minutes post-insufflation. The results were analyzed using multivariate analysis of variance for repeated measures with a P <.05. A power of 0.9 was obtained to identify changes over time.Results: During the time course of the study the hemodynamic, metabolic, and hormonal parameters showed significant alterations. The most dramatic hemodynamic changes occurred post-insufflation characterized by a decrease in cardiac index and stroke volume with a concurrent increase in systemic vascular resistance. The metabolic parameters showed a significant decrease in pH and corresponding increase in PaCO(2). However, the pH and PaCO(2) remained within normal limits through the study. As part of the study's protocol the investigators increased minute volume to control for a rise in PaCO(2) during the procedure. A significant increase was noted in aldosterone and arginine vasopressin at post-insufflation and Trendelenburg positioning. Plasma renin activity showed a dramatic increase following post-insufflation. None of the subjects developed any post anesthetic complications.Conclusion: Our study demonstrated that pneumoperitoneum and Trendelenburg positioning cause statistically significant elevations in the stress hormones and concurrently cause a decrease in hemodynamic parameters. A healthy patient may tolerate these changes but a patient with cardiovascular disease or pulmonary problems may not be able to compensate as efficiently.

Objective assessment of "cardioprotective" efficacy as a prognostic guide to management of mildly symptomatic revascularizable coronary artery disease.

OBJECTIVES: The concept of "cardioprotection" based on ejection fraction was tested to see whether patients with coronary artery disease in whom medical treatment fails to be cardioprotective can be distinguished from those in whom it is safe to continue such treatment. BACKGROUND: Ejection fraction is of fundamental prognostic importance. Its modification by anti-ischemic medication may allow assessment of cardioprotection from adverse outcome. METHODS: Exercise ejection fraction and the change in ejection fraction from rest to exercise were measured by radionuclide ventriculography with and without background medication in 102 mildly symptomatic patients with coronary artery disease suitable for revascularization but initially treated medically. RESULTS: Over 20 months, 23 patients experienced an adverse event. With medication, exercise ejection fraction increased in patients with and without events. By contrast, the ejection fraction response to exercise improved significantly in the event-free group only; the group with events had a persistent decrease in ejection fraction. By Cox analysis, the ejection fraction response to exercise performed with medication made the most significant independent contribution to event-free survival. Comparison of areas under receiver operating characteristic curves suggested that this index is the most useful clinical measure of cardioprotection. CONCLUSIONS: An exercise-induced decrease in ejection fraction despite anti-ischemic medication implies failure of cardioprotection and a greater short-term risk of adverse outcome and crossover to revascularization in patients initially treated medically. Conversely, a preserved left ventricular performance confers a satisfactory prognosis while continuing with that treatment. Thus, the effect of medication on the ejection fraction response to exercise--a reasonable estimate of its cardioprotective efficacy--may influence the choice of continuing with such treatment or performing early revascularization.

Exercise testing without interruption of medication for refining the selection of mildly symptomatic patients for prognostic coronary angiography.

OBJECTIVE: To examine how exercise testing on background medical treatment affects the ability of the test to predict prognostically important patterns of coronary anatomy in patients with a high clinical probability of coronary artery disease but who are well controlled on medication. DESIGN: Prospective study. SETTING: Regional cardiothoracic centre and referring district general hospital. PATIENTS: 84 patients with a history of typical angina or definite myocardial infarction and mild symptoms who had been placed on the waiting list for prognostic angiography. INTERVENTION: Maximal exercise electrocardiography and radionuclide ventriculography performed off and on medication, followed by angiography within three months. MAIN OUTCOME MEASURE: Prognostically important coronary artery disease for which early surgery might be recommended purely on prognostic grounds, irrespective of symptoms. RESULTS: Coronary artery disease was present in 71/84 (85%) patients; in 28/84 (33%) patients this was prognostically important. When the result was strongly positive, the predictive accuracy for prognostically important disease was 0.46 off and 0.62 on medication for the exercise electrocardiogram and 0.71 off and 0.82 on medication for exercise radionuclide ventriculography. The likelihood ratio was 1.00 off and 1.36 on medication for exercise electrocardiography and 2.54 off and 10.5 on medication for exercise radionuclide ventriculography. In stepwise logistic regression, the test identified as the strongest predictor of prognostically important disease was exercise radionuclide ventriculography on medication for which the improvement chi 2 was 28 (p < 0.0001). With the regression model, the probability of important disease is 92% if exercise radionuclide ventriculography on medication is at least strongly positive, compared with 16% if the result is normal or just positive. CONCLUSION: In patients likely to have coronary disease, exercise testing should be performed without interruption of medication to optimise its ability to identify those with prognostically important disease, and to help to avoid unnecessary or premature angiography in those who are well controlled on medical treatment.

Suppression of inducible painless myocardial ischemia by conventional medical therapy: effect on short-term outcome and left ventricular systolic function.

To test the hypothesis that abolition of exercise-induced painless myocardial ischemia by anti-ischemic medication improves prognosis in patients with medically treated coronary artery disease, we studied such patients with painless ischemia during exercise radionuclide ventriculography performed after temporary discontinuation of medication. The test was repeated while patients received conventional medical therapy that rendered angina no worse than New York Heart Association class I. The relative risk of adverse cardiac events was reduced by > 5-fold when painless ischemia was abolished by symptom-dictated therapy. Thus, the abolition of exercise-induced painless ischemia by conventional medical therapy carries a better short-term prognosis in medically treated coronary artery disease, suggesting that therapeutic efficacy may need to be assessed by titration against ischemia and not angina. In patients without overt cardiac events, there were no significant differences between baseline and 12-month measurements of ejection fraction at rest, peak exercise, and the change in ejection fraction from rest to exercise. Thus, in those who remain asymptomatic and event-free, painless ischemia that is easily inducible at baseline despite medication does not lead per se to deterioration of left ventricular systolic function at rest or during exercise over 12 months. Such an effect, if evident as early as at 12 months, would favor a strategy of early revascularization over medical treatment in asymptomatic patients who have inducible painless ischemia despite medication.

Long-term effect of inducible silent ischaemia on left ventricular systolic function.

Silent myocardial ischaemia is readily detected by exercise radionuclide ventriculography in patients with coronary artery disease. In those who remain asymptomatic and event-free, it is not known whether silent ischaemia which is inducible despite anti-ischaemic medication exerts an insidious detrimental effect on left ventricular function. To study this, 34 medically treated patients (mean age 57; 26 men) underwent prospective measurement of left ventricular ejection fraction (LVEF) during rest and exercise radionuclide ventriculography without interruption of anti-ischaemic medication at baseline and 12 months later. There was no significant mean (standard deviation, 95% confidence interval) deterioration from baseline to 12 months in LVEF at rest (50% v 49%, SD 5; 95% CI = -3 to +1), peak exercise (44% v 45%, SD 8; 95% CI = -1 to +4) and the change in LVEF from rest to exercise (-6% v -4%, SD 7; 95% CI = -1 to +5). Thus, in coronary artery disease patients who remain asymptomatic and event-free on medical therapy, silent myocardial ischaemia which is readily inducible at baseline despite medication does not lead per se to deterioration of left ventricular systolic function at rest or exercise over 12 months.

Novel approach to the interpretation of long-term "deterioration" in ejection fraction in individual patients with coronary artery disease.

OBJECTIVE: The long-term predictability of left ventricular ejection fraction (LVEF) measurements was evaluated with particular emphasis on the assessment of deterioration in individual patients whose coronary artery disease was initially treated medically. DESIGN: Prospective pilot study. SETTING: Regional cardiac centre. PATIENTS: 60 minimally symptomatic patients with coronary artery disease who, after arteriography, were initially treated medically. INTERVENTION: Measurement of LVEF by first pass exercise radionuclide ventriculography at baseline and six months later without interruption of usual anti-ischaemic medication. Baseline and six-month studies were analysed independently of each other. MAIN OUTCOME MEASURE: Based on 51 patients who remained event free, 95% prediction intervals were derived for prognostic LVEF indices to suggest the minimum change from baseline that might be considered clinically important in the individual patient, alerting clinicians to the need for closer review. RESULTS: At six-month ventriculography, 22 patients showed apparent deterioration in exercise LVEF or the change in LVEF with exercise (delta LVEF). Only two patients had six-month values below the lower limit of 95% prediction intervals, compared with 15 when 95% group confidence intervals (z = 3.33, p < 0.001) were used. When delta LVEF = 0 at baseline, the lower limit of 95% prediction intervals allowed for an exercise induced fall at six months of < or = 13%. For a baseline exercise LVEF of 50% (just normal), the lower limit of 95% prediction intervals was 38%--that is, the exercise LVEF could be measured as low as 38% > or = six months later without necessarily indicating or missing true deterioration. CONCLUSION: In the follow up of minimally symptomatic patients with coronary artery disease, serial long-term changes, in particular "deterioration," in prognostic LVEF indices may be interpreted more meaningfully with reference to 95% prediction intervals.

Effect on prognosis of abolition of exercise-induced painless myocardial ischemia by medical therapy.

During exercise radionuclide ventriculography, many patients with coronary artery disease exhibit painless myocardial ischemia defined as an abnormal left ventricular ejection fraction response without accompanying angina. To see if complete suppression of such exercise-induced painless ischemia by anti-ischemic medication implies a better prognosis in medically treated coronary artery disease, 34 patients underwent repeat testing at 4 weeks receiving regular conventional therapy that rendered angina no worse than class I. With such therapy, painless ischemia was abolished in 12 patients (group I) and persisted in 22 (65%, group II). Both groups were similar in age, number of diseased vessels, proportion with previous myocardial infarction, exercise ejection fraction, and degree of exercise-induced painless ischemia at baseline. At 9 months, adverse events had occurred in 11 patients (2 patients with myocardial infarction, 4 with unstable angina, 2 with angioplasty and 3 with bypass surgery). Only 1 of 12 patients (8%) in group I had experienced events compared with 10 of 22 (45%) in group II (chi-square, 5.4; p less than 0.025; 95% confidence interval, 12 to 61%). Thus, the relative risk of adverse events in patients whose painless ischemia was abolished was only 18% of that in patients in whom it was persistent. These results suggest that (1) the abolition of exercise-induced painless ischemia by conventional symptom-dictated medical therapy confers a better short-term prognosis in medically treated coronary artery disease, and (2) therapeutic efficacy may need to be assessed by titration against ischemia and not against angina.

Early prognosis after thrombolysis: value of exercise radionuclide ventriculography performed on anti-ischaemic medication.

We examined the prognostic value of exercise radionuclide ventriculography (RNV) performed on anti-ischaemic medication following thrombolysis. Within 3 months of thrombolysis for first myocardial infarction, 31 medically treated patients with revascularisable but non-critical and minimally symptomatic coronary disease had left ventricular ejection fraction (LVEF) measured by first-pass exercise RNV. This was first performed off treatment and then repeated within 4 weeks on patients' regular medication. Follow-up at 12 months post-thrombolysis showed that 5 patients (Group I) had suffered significant recurrent symptoms (worsening angina requiring revascularisation in 3, unstable angina in 1, reinfarction in 1), but 26 remained well (Group II). Both groups were similar in age, post-thrombolytic severity of coronary disease, exercise LVEF whether off (39% vs 43%) or on medication (43% vs 44%), and change in LVEF with exercise ([symbol: see text]LVEF) off medication (-11% vs - 3%). However, on medication, there was a significant difference in mean [symbol: see text]LVEF between Groups I and II (-11% vs + 5%, P = 0.0008, 99% confidence interval = 4 to 26%). Thus, following thrombolysis, an abnormal [symbol: see text]LVEF despite anti-ischaemic medication may identify patients at risk of significant early recurrent ischaemia. Post-thrombolysis prognostic testing by exercise RNV may therefore be of greater value when performed on rather than off medication.

Influence of respiratory variations on right ventricular function.

Respiratory effort during inspiration, expiration, and the Valsalva manoeuvre changes right ventricular preload and afterload. On inspiration these changes should improve systolic emptying of a larger end diastolic volume and so increase the ejection fraction, whereas on expiration the reverse should be true. The resting right ventricular ejection fraction was measured by first pass radionuclide angiography with gold-195m (half life 30.5 s) in 17 individuals at maximal inspiration and expiration and in eight at rest and during the strain phase (phase 2) of the Valsalva manoeuvre. The right ventricular ejection fraction was significantly lower during expiration than during inspiration. There were, however, no significant differences in bolus duration or right ventricular transit time. The Valsalva manoeuvre, in contrast, significantly increased the ejection fraction and also significantly prolonged both the bolus duration and right ventricular transit time. The conformation of the bolus curves during the Valsalva manoeuvre suggested the development of tricuspid regurgitation. These data suggest that relative influences of venous return, pulmonary arterial pressure, pulmonary vascular resistance, and possible functional tricuspid regurgitation vary during inspiration, expiration, and the Valsalva manoeuvre and can affect the right ventricular ejection fraction. Changes in right ventricular function on exercise assessed by first pass radionuclide angiography must be interpreted with caution because maximal respiratory effort may alter the right ventricular ejection fraction independently of ischaemia or other non-ischaemic factors.

Relation between coronary anatomy and serial changes in left ventricular function on exercise: a study using first pass radionuclide angiography with gold-195m.

Serial changes in left ventricular function on exercise were assessed by first pass radionuclide angiography with gold-195m (half life 30.5 s) in 25 men with known coronary anatomy. In the seven patients with three vessel disease, abnormalities of global left ventricular function and regional wall motion occurred earlier during exercise, were of greater extent at peak exercise, and persisted longer after exercise than in the 11 patients with one and two vessel disease or the seven with normal coronary arteries. Although there were significant differences between the groups in absolute change in ejection fraction and the rate of change in ejection fraction related to exercise duration and heart rate, a considerable overlap of values between groups precluded the accurate prediction of coronary anatomy in individuals. These data suggest that the amount of myocardium at risk from ischaemia in some patients with one and two vessel disease may resemble that in patients with three vessel disease. This study shows that an anatomical classification based solely on the number of diseased vessels will not predict the extent of the impairment of left ventricular function on exercise.