Evaluating the cost-effectiveness of polygenic risk score-stratified screening for abdominal aortic aneurysm.

As the heritability of abdominal aortic aneurysm (AAA) is high and AAA partially shares genetic architecture with other cardiovascular diseases, genetic information could help inform AAA screening strategies. Exploiting pleiotropy and meta-analysing summary data from large studies, we construct a polygenic risk score (PRS) for AAA. Leveraging related traits improves PRS performance (R2) by 22.7%, relative to using AAA alone. Compared with the low PRS tertile, intermediate and high tertiles have hazard ratios for AAA of 2.13 (95%CI 1.61, 2.82) and 3.70 (95%CI 2.86, 4.80) respectively, adjusted for clinical risk factors. Using simulation modelling, we compare PRS- and smoking-stratified screening with inviting men at age 65 and not inviting women (current UK strategy). In a futuristic scenario where genomic information is available, our modelling suggests inviting male current smokers with high PRS earlier than 65 and screening female smokers with high/intermediate PRS at 65 and 70 respectively, may improve cost-effectiveness.

Pathological and immunological study of an in ovo complex vaccine against infectious bursal disease.

The appearance of very virulent strains of infectious bursal disease (IBD) virus at the end of the 1980s made it necessary to develop more effective immunization procedures. To facilitate this, the immunogenicity and the immunosuppressive effect of a mild (G-87), an intermediate (LIBD) and an intermediate-plus (IBDV 2512) IBDV strain were tested after the in ovo inoculation of 18-day-old SPF and broiler chicken embryos. It was established that no noteworthy difference existed between the immunized and the control embryos in hatching rate and hatching weight. The higher the virulence of the vaccine virus strain, the more severe damage it caused to the lymphocytes of the bursa of Fabricius. In SPF chickens, the haemagglutination inhibition (HI) titres induced by a Newcastle disease (ND) vaccine administered at day old decreased in inverse ratio to the virulence of the IBD vaccine strain, while in broiler chickens this was not observed. Despite the decrease of the HI titre, the level of protection did not decline, or did so only after the use of the 'hot' strain. SPF chickens immunized in ovo with a complex vaccine prepared from strain IBDV 2512 and IBD antibody showed the same protection against Newcastle disease as the broilers. In broiler chicken embryos immunized in ovo, only strain IBDV 2512 induced antibody production, and such chickens were protected against IBD at 3 weeks of age. The complex vaccine administered in ovo has been used successfully at farm hatcheries as well.

Intravascular magnetic resonance imaging of aortic atherosclerotic plaque composition.

Magnetic resonance imaging (MRI) may be an excellent tool to define atherosclerotic plaque composition, but surface MRI (SMRI) suffers from a low signal-to-noise ratio and low resolution of arterial images. Intravascular MRI (IVMRI) represents a potential solution for acquiring high-quality in vivo images of atherosclerotic plaques. Isolated segments of 11 thoracic human aortas obtained at autopsy were imaged by IVMRI using an intravascular receiver catheter coil designed and built at our institution. Images obtained by IVMRI were compared with corresponding images obtained by SMRI and with histopathological aortic cross sections. The intensity of intimal thickness and plaque components was graded by IVMRI and histopathology using a score of 1 for mild, 2 for moderate, and 3 for severe intensity. IVMRI had an agreement of 75% with histopathology in fibrous cap grading (37.5% expected, kappa = 0.60, P < 0.001) and of 74% in necrotic core grading (39% expected, kappa = 0.57, P < 0.001). Intraplaque calcification was correctly graded by IVMRI in six of the eight plaques in which histopathology recognized calcium. The analysis of intimal thickness showed 80% agreement between IVMRI and histopathology (52% expected, kappa = 0.59, P < 0.001). IVMRI image features were similar to those of SMRI. In addition, IVMRI accurately determined atherosclerotic plaque size in comparison with histopathology and SMRI (slope = 1.25 cm2, r = 0.99, P < 0.001 for luminal area by IVMRI vs histopathology; slope = 0.97 cm2, r = 0.996, P < 0.001 for luminal area by IVMRI vs SMRI). IVMRI has the potential to provide important prognostic information in patients with atherosclerosis because of its ability to accurately assess both plaque composition and size.

High resolution intravascular MRI and MRS by using a catheter receiver coil.

Potentially important diagnostic information about atherosclerosis can be obtained by using magnetic resonance imaging and spectroscopy techniques. Because critical vessels such as the aorta, coronary arteries, and renal arteries are not near the surface of the body, surface coils are not adequate to increase the data quality to desired levels. A few catheter MR receiver coil designs have been proposed for imaging the walls of large blood vessels such as the aorta. These coils have limited longitudinal coverage and they are too thick to be placed into small vessels. A flexible, long and narrow receiver coil that can be placed on the tip of a catheter and will enable multi-slice high resolution imaging of small vessels has been developed. The authors describe the theory of the coil design technique, derive formulae for the signal-to-noise ratio characteristics of the coil, and show examples of high resolution cross-sectional images from isolated human aortas acquired by using this catheter coil. In addition, high resolution in vivo rabbit aorta images were obtained as well as a set of spatially resolved chemical shift spectra from a dog circumflex coronary artery.

Predicting use of hearing protection: a preliminary study.

The National Institute of Occupational Safety and Health targeted noise-induced hearing loss as one of the top 10 occupational hazards. Research has been directed toward reducing noise exposure rather than identifying the factors associated with workers' decision consistently to use hearing protection. The long-term goal of this program of research is to develop a causal model explaining workers' use of hearing protection to guide development of nursing interventions. This study was a preliminary one to prepare for testing Pender's health-promotion model (HPM) as a causal model. Ninety-eight skilled tradesmen completed written questionnaires at their work site. Although 98% indicated they were supposed to wear protection, their reported use averaged 50.3% of the time. Reported use significantly and positively correlated with workers' perceptions of the benefits and self-efficacy of use, value of outcomes regarding keeping out noise and increased well-being, and health-promoting behaviors in the areas of self-actualization and stress management. Perceptions of barriers of use were significantly and negatively related to use. In regression analyses of use of hearing protection on components of the HPM and dimensions of health behavior and lifestyle, one component of the HPM (benefits) and two dimensions of health behavior and lifestyle (self-actualization and interpersonal support) significantly predicted use, accounting for 24% of the variance in use of protection. Knowledge of the predictors of hearing protection use will ultimately aid nurses in implementing interventions, increasing use, and decreasing hearing losses.

Appendicitis diagnosis today: clinical and ultrasonic deductions.

A total of 111 patients referred with a diagnosis of suspected "appendicitis" were entered into a prospective study. The surgeon and radiologist in charge of ultrasonography made separate diagnoses, and their findings were then combined and discussed as indications for surgery. Clinically, a history of pain migration proved to be reliable (p < 0.0001) as a diagnostic indicator, in contrast to nausea and initial irregularity of bowels. The duration of symptoms was significantly shorter in patients with proved appendicitis than among patients with negative findings (median 24 hours compared with 41 hours, p < 0.04). Among patients with perforated appendicitis, the symptomatic history was prolonged (not significantly) by 3 hours. Peritoneal signs such as pain on percussion, rebound tenderness, guarding, and a leukocytosis of more than 13,000/mm3 were indicative of appendicitis (p = 0.0001 for each sign). Lively bowel sounds excluded the possibility of appendicitis (p = 0.001). Scanty bowel sounds, rectal tenderness, axillorectal temperature difference, and a left shift in leukocytes were of no diagnostic significance. The doctor's "clinical experience" is significant at the level of p < 0.03. On ultrasonography, the following signs were indicative of appendicitis: periappendicular infiltration (p = 0.0003), a visible "cockade," and an appendix larger than 12 mm in diameter (p = 0.04). For 75% of the patients the surgeon was sure of his own clinical diagnosis and did not allow himself to be influenced by the sonographic findings. In 12% of doubtful cases ultrasonographic results decisively favored operation, and in 4.5% (n = 5) it prevented an unnecessary laparotomy in the presence of positive clinical symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

[Diagnostic significance of clinical symptoms versus ultrasonography in appendicitis. A prospective study]. / Diagnostischer Stellenwert von Klinik versus Sonographie bei Appendizitis. Eine prospektive Studie.

The aim of the presented study was to find what importance ultrasonography has in the diagnosis of acute appendicitis compared to clinical findings and on the surgeon's decision regarding to laparotomy. 111 patients entering the emergency station with suspected appendicitis were evaluated in a prospective clinical study. Surgeon and radiologist had to commit themselves to the diagnosis, afterwards signs were discussed. Clinical accuracy over all was 89%. Pain migration and peritonitis signs corresponded significantly with appendicitis (p less than 0.0001). The appendix was well seen in sonographic examination in 32% (accuracy 80%), in 27% was doubtful (accuracy 70%), and in 41% the appendix could not be demonstrated. Diameter of a normal appendix was 8 mm compared to 12 mm for an inflamed appendix (p less than 0.05). Rates negative laparotomies decreased from 16% to 12.7%. The surgeon was not influenced by sonography in 75%. In 12% ultrasonography decided for laparotomy and in 4.5% sonography prevented operation. We conclude from our results, that sonography reduces the negative laparotomy rate. Ultrasonography is especially useful in doubtful clinical pictures. Clinical findings and experience remain of major importance in appendicitis-diagnosis.

[Does sonography help in the diagnosis of appendicitis?]. / Hilft die Sonographie in der Diagnostik der Appendizitis?

The aim of the presented study was to find whether improvement has ultrasonography in the diagnosis of acute appendicitis and on surgeon's decision referring to laparotomy. 111 patients entering into the emergency station with suspected appendicitis were evaluated in a prospective clinical study. Surgeon and radiologist had to commit themselves to the diagnosis, afterwards signs were discussed. In 32% the appendix was well seen (accuracy 80%), in 27% sonographic examination was doubtful (accuracy 70%) and in 41% the appendix could not be demonstrated. Diameter of normal appendix was 8 mm compared to inflamed appendix with 12 mm (p less than 0.05). The negative laparotomy decreased from 16% to 12.7%. Surgeon was not influenced by sonography in 75%. In 12% ultrasonography decided for laparotomy and in 4.5% sonography prevented operation. We conclude from our results, that sonography reduces negative laparotomy rate. Especially ultrasonography is useful in doubtful clinical pictures.

Exercise training combined with antihypertensive drug therapy. Effects on lipids, blood pressure, and left ventricular mass.

We studied exercise training combined with the use of antihypertensive drugs and examined the following questions. (1) Are there additive antihypertensive benefits with exercise and drug therapy combined? (2) Does drug therapy limit exercise-induced lipid improvements? (3) Does exercise that includes weight training and walking/jogging affect the left ventricle? Fifty-two hypertensive men were randomly assigned, double-blind, to diltiazem hydrochloride, sustained release (360 mg daily), propranolol hydrochloride (240 mg daily), or placebo and exercised three times per week for 10 weeks. Baseline blood pressure (145/97 mm Hg) fell after training (131/84 mm Hg) in all groups. Exercise decreased total and low-density lipoprotein cholesterol levels in all groups. Increases in the levels of high-density lipoprotein cholesterol were similar in placebo and diltiazem groups, whereas the propranolol group changed in an opposite direction. In all groups, left ventricular mass increased with training, while diastolic function was unchanged. We conclude that (1) drug therapy provided no additive benefit to the antihypertensive effects of exercise, (2) propranolol limited improvements in high-density lipoprotein cholesterol, and (3) exercise did not adversely affect the left ventricle.

Effects of diltiazem or propranolol during exercise training of hypertensive men.

This was a prospective, randomized, double-blind, placebo-controlled trial to establish whether beta blockers or calcium-channel blockers limit exercise capacity and training responses in men with mild hypertension. Circuit weight and aerobic training was used to assess the effects of drugs on cardiovascular fitness and muscle strength. Fifty-two sedentary men, ages 25-59 yr, with a diastolic blood pressure of 90-105 mm Hg off drugs, without significant ST depression during maximal stress testing, received diltiazem, propranolol, or placebo. Maximal oxygen uptake (VO2max) and exercise duration during treadmill testing, as well as one-repetition maximal strength, were assessed on eight weight machines after a single-blind placebo baseline, after 2 wk of drug run-in, and after 10 wk of exercise training. Total daily doses were 240 mg for propranolol and 360 mg for diltiazem. Propranolol decreased VO2max after drug run-in (P less than 0.05). Exercise training increased VO2max (P less than 0.05) in the diltiazem and placebo groups. After training VO2max in the propranolol group increased (P less than 0.05) from run-in but not beyond baseline levels. Thus, the reduction of VO2max consequent to propranolol therapy limited the overall benefits of training. Exercise duration did not change with run-in and increased (P less than 0.05) with training by 22%, 19%, and 10% for the diltiazem, placebo, and propranolol groups, respectively. Strength after run-in was unchanged, and exercise training increased strength (P less than 0.0001) on all weight machines in all groups. The results show an advantage of diltiazem to propranolol, particularly among physically active patients engaged in aerobic exercise who require antihypertensive therapy.

Resistive training safety and assessment guidelines for cardiac and coronary prone patients.

The past few years have seen increased use of resistive training programs for cardiac and coronary prone individuals. There is growing evidence that using moderate resistance with frequent repetitions is safe and beneficial. This review provides guidelines for selection and assessment of patients for resistive training programs. For the most part, the criteria for participation in resistive training are the same as those used for the more traditional cardiac and high risk exercise programs.

Affinity labeling of delta-opiate receptors using [D-Ala2,Leu5,Cys6]enkephalin. Covalent attachment via thiol-disulfide exchange.

[D-Ala2,Leu5,Cys6]Enkephalin (DALCE) is a synthetic enkephalin analog which contains a sulfhydryl group. DALCE binds with high affinity to delta-receptors, with moderate affinity to mu-receptors, and with negligible affinity to kappa-receptors. Pretreatment of rat brain membranes with DALCE resulted in concentration-dependent loss of delta-binding sites. Using 2 nM [3H][D-Pen2,D-Pen5]enkephalin (where Pen represents penicillamine) to label delta-sites, 50% loss of sites occurred at about 3 microM DALCE. Loss of sites was not reversed by subsequent incubation in buffer containing 250 mM NaCl and 100 microM guanyl-5'-yl imidodiphosphate (Gpp(NH)p), conditions which cause dissociation of opiate agonists. By contrast, the enkephalin analogs [D-Ala2,D-Leu5]enkephalin, [D-Ser2,Leu5,Thr6]enkephalin, [D-Pen2,D-Pen5]enkephalin, and [D-Ala2,D-Leu5,Lys6]enkephalin were readily dissociated by NaCl and Gpp(NH)p, producing negligible loss at 3 microM. This suggests that DALCE binds covalently to the receptors. Pretreatment of membranes with the reducing agents dithiothreitol and beta-mercaptoethanol had no effect on opiate binding. Thus, loss of sites required both specific recognition by opiate receptors and a thiol group. The irreversible effect of DALCE was completely selective for delta-receptors. Pretreatment with DALCE had no effect on binding of ligands to mu- or kappa-receptors. The effect of DALCE on delta-binding was: 1) markedly attenuated by inclusion of dithiothreitol in the preincubation buffer, 2) partially reversed by subsequent incubation with dithiothreitol, 3) slightly enhanced when converted to the disulfide-linked dimer, and 4) prevented by blocking the DALCE sulfhydryl group with N-ethylmaleimide or iodoacetamide. These results indicate that DALCE binds covalently to delta-receptors by forming a disulfide bond with a sulfhydryl group in the binding site. The mechanism may involve a thiol-disulfide exchange reaction.

Self-efficacy mediates strength gains during circuit weight training in men with coronary artery disease.

Motivation to engage in health-promoting exercise has been ascribed to global personality traits such as self-esteem or athletic self-confidence. Self-Efficacy Theory challenges this view by proposing that highly specific estimates of personal capabilities mediate adoption of new or difficult behavior patterns. We tested this assumption by measuring self-efficacy perceptions in 40 men with coronary artery disease who participated in an experiment evaluating effects of circuit weight training (CWT). Specific self-efficacy estimates were assessed during baseline strength/endurance testing and after 10 wk participation in CWT or volleyball. Correlational analyses of self-efficacy in relation to performance on strength/endurance tests strongly supported the contention that adoption of novel activities is governed by highly specific self-perceptions. Participation in CWT produced greater strength and endurance gains than did volleyball, and these changes were accompanied by increased self-efficacy in CWT subjects for activities resembling the training tasks. The assertion that self-efficacy perceptions directly mediate involvement in challenging physical activities was supported by multiple regression analyses. These revealed that pre-training self-efficacy judgments predicted post-test strength gains even after controlling for baseline strength, type of training and frequency of participation in exercise sessions.

The preoperative electrocardiogram as an indicator of risk in major noncardiac surgery.

In this series of 198 patients studied prospectively before major noncardiac surgery, we previously reported that an abnormal preoperative electrocardiogram was a statistically significant independent predictor of an increased risk of postoperative complications, i.e., death, myocardial infarction, or myocardial ischemia. We therefore carried out a detailed analysis of the preoperative electrocardiographic (ECG) findings using Minnesota code criteria. Both ST-T abnormalities and intraventricular conduction delays showed a statistical trend toward a higher frequency in patients with a complicated vs. an uncomplicated postoperative course (82% vs. 59% and 24% vs. 7%, respectively). Although only a minority of patients with either ECG finding actually developed a complication (22% and 40% respectively), the preoperative ECG appears to be a useful screening method, with ST-T abnormalities and intraventricular conduction delays identifying patients at increased risk for postoperative complications.

Usefulness of self-efficacy in predicting overexertion during programmed exercise in coronary artery disease.

Overexertion during group jogging was evaluated in relation to self-perceived functional capacity and ability to self-monitor exertional heart rate in 40 men, mean age 55 +/- 9 years, with documented coronary artery disease. Patients' confidence in their ability to jog various distances was measured with a jog self-efficacy (SE) scale before a group exercise program was begun. Depression, type A personality, and performance of symptom-limited treadmill exercise were also assessed. Later, each patient was monitored with ambulatory (Holter) electrocardiography during programmed group jogging. Ambulatory monitoring disclosed significant noncompliance with exercise prescriptions: 33% of patients exceeded their prescribed range of 70% to 85% of maximal treadmill heart rate for at least 10 minutes of the 20-minute exercise bout. Another 25% spent 10 minutes or longer exercising below the prescribed range. Pretest jog SE predicted the number of minutes patients exercised above or below the prescribed intensity, but depression, type A and treadmill performance measures did not. Self-monitoring accuracy (the amount of agreement between exercise heart rate recorded by the electrocardiogram and by the patient) was also related to the number of minutes patients exercised outside the prescribed range. Comparison of SE and self-monitoring accuracy variables revealed that "overachievers" were patients who overestimated their ability to jog, while "underachievers" were those who overestimated their heart rate during exercise. Self-perceptions and self-monitoring skills appear to be important independent predictors of behavioral compliance to exercise guidelines.

Circuit weight training in cardiac patients.

This was a prospective, randomized evaluation of the safety and efficacy of 10 weeks of circuit weight training in patients, aged 35 to 70 years, with documented coronary artery disease. Circuit weight training refers to the performance of a series of weight-lifting exercises using a moderate load with frequent repetitions. Patients had participated in a supervised cardiac rehabilitation program for a minimum of 3 months before the study. Control patients (n = 20) continued with their regular exercise consisting of a walk/jog and volleyball program, while the experimental group (n = 20) substituted circuit weight training for volleyball. No sustained arrhythmias or cardiovascular problems occurred. The experimental group significantly increased treadmill time from 619 to 694 seconds while the treadmill time of the control group did not change. Strength in the experimental group increased by an average of 24% while there was no change in the control patients. Circuit weight training appears to be safe, and to result in significant increases in aerobic endurance and musculoskeletal strength compared with traditional exercise used in cardiac rehabilitation programs.

Characterization of D-Ala2,Leu5,Cys6-enkephalin: a novel synthetic opioid peptide with slowed dissociation from delta receptors.

D-Ala2,Leu5,Cys6-enkephalin (DALCE) is a synthetic enkephalin analog which contains a reduced sulfhydryl group. It exhibited moderate delta selectivity (mu/delta IC50 ratio 13), but was not as selective as the disulfide-containing peptide, D-Pen2,5-enkephalin (DPDPE) (mu/delta ratio 1121). However, unlike other delta-selective peptides, DALCE exhibited a markedly slowed dissociation from receptors after pretreatment of membranes with micromolar concentrations. Pretreatment of membranes with 10 uM DALCE, followed by extensive washing, produced an 85-90% loss of 3H-DPDPE binding sites. D-Ala2,D-Leu5-enkephalin (DADLE), D-Ser2,Leu5,Thr6-enkephalin (DSTLE) and DPDPE produced losses of 59%, 70%, and 19%, respectively. The effect of DALCE was not reversed by a 60 min post-incubation in buffer containing 250 mM NaCl + 100 uM GMPPNP, a condition which produced nearly complete reversal of loss of sites by DADLE and DSTLE. DPDPE could be dissociated merely by post-incubation in TRIS-buffer alone for 15 min. The order for ease of dissociation after preincubation was DPDPE much greater than DADLE greater than DSTLE much greater than DALCE. The effect of DALCE was selective for delta sites, although higher concentrations of DALCE produced loss of mu sites. DALCE pretreatment had no effect on recovery of kappa sites. These results indicate that DALCE binds essentially irreversibly to delta receptors.