Age-related differences in warning symbol comprehension and training effectiveness: effects of familiarity, complexity, and comprehensibility.

Age-related changes in selective attention, inhibitory efficiency, and the ability to form new associations suggest that older adults may have greater difficulty with more complex and less comprehensible symbols. We examined comprehension of symbols varying in terms of ratings of familiarity, complexity, and comprehensibility, by younger (aged 18-35) and older (aged 55-70) adults. It was found that older adults have greater difficulty than younger adults in comprehending warning symbols and that accident scenario training improves comprehension. Regression analyses indicated that familiarity and comprehensibility were important in determining performance on the pre-training comprehension test by both younger and older adults. However, training eliminated the effects of stimulus characteristics for younger adults, while older adults' comprehension continued to be significantly influenced by comprehensibility. We suggest that symbol design incorporates cues to knowledge to facilitate the linkage between new knowledge (i.e. the warning symbol) and relevant knowledge in long-term memory. Statement of Relevance: Symbol characteristics play an important role in age-related differences in warning symbol comprehension. To optimise comprehension by older adults, symbols should have a clear relationship with areal-world referent. Alternatively, symbol design could incorporate cues to knowledge to facilitate the linkage between new knowledge and relevant knowledge in long-term memory.

Enhanced protein synthesis in a cell-free system from hypertrophied skeletal muscle.

Hypertrophy of the rat soleus muscle was induced by tenotomy of the synergistic muscles. Four days after the operation, the weight of the muscle had increased by 30 percent. The hypertrophied muscle had an increased concentration of DNA and RNA, when compared to the contralateral control soleus. Although the amount of myofibrillar protein increased during the 4-day period, the concentration of this component decreased. Microsomes prepared from hypertrophied muscle had an increased RNA concentration. The combined microsomes and pH-5 enzyme from hypertrophied muscle supported a faster rate of protein synthesis in vitro than the same system prepared from an equal weight of contralateral muscle which was used as a control.

Changing drivers' attitudes towards mobile phone use through participative simulation testing and feedback.

OBJECTIVE: To assess the effectiveness of a simulation-based participative and feedback approach to change drivers' attitudes towards mobile phone use while driving. METHODS: 30 experienced drivers were tested. Five scenarios were developed to test drivers' performance with and without a secondary mobile phone task on a medium-fidelity fixed base driving simulator. The treatment group received feedback in the form of video playback of their driving performance, while the control group did not receive any feedback. Attitudes towards mobile phone use were assessed by a questionnaire before, immediately after, and again one month following the experiment to determine the duration of feedback effects. RESULTS: All 30 drivers reported willingness to engage in driving and talking on a mobile phone in some situations. The results of the simulated driving test showed that a secondary mobile phone task significantly degraded driving performance. The treatment group showed significant attitude change towards mobile phone use while driving; the control group had no attitude change. At the one month follow-up, a continued benefit of feedback was reflected in driver attitudes in the treatment group. CONCLUSIONS: Participative driving using simulation is a useful tool to demonstrate driving performance degradation in dual task conditions. It was found that feedback in the form of simulation playback is effective in changing drivers' attitudes towards mobile phone use and that attitude change is maintained over a follow-up period of one month.

Regulation of cathepsin D metabolism in rabbit heart: evidence for a role for precursor processing in the control of enzyme activity.

Production of active lysosomal enzymes may involve limited proteolysis of inactive high molecular weight precursors. Precursor processing potentially regulates lysosomal enzyme activity. To test whether rabbit cardiac cathepsin D is first synthesized as a precursor and whether prolonged fasting (a condition affecting both cathepsin D and total cardiac protein turnover) influences precursor processing, rates of cathepsin D synthesis and processing were compared in left ventricular slices of control and 3-d-fasted rabbits incubated in vitro with [(35)S]methionine. (35)S-labeled cathepsin D was isolated by butanol-Triton X-100 extraction, immunoprecipitation, and dodecyl sulfate-polyacrylamide gel electrophoresis. Total cardiac protein synthesis was measured by tracer incorporation and normalized for differences in precursor pool size by direct measurement of [(35)S]aminoacyl-tRNA-specific radioactivity. Relative cathepsin D synthetic rates were obtained by comparing (35)S incorporation into cathepsin D with (35)S incorporation into all cardiac proteins. Enzyme processing was assessed in pulse-chase experiments and assayed by autoradiography. The results indicate that (a) rabbit cardiac cathepsin D is synthesized as a precursor (53,000 mol wt) that is processed to a 48,000-mol wt form, (b) rates of both cathepsin D and total cardiac protein synthesis are similar in control and fasted rabbits, suggesting that decreased enzyme degradation rather than increased synthesis is responsible for the elevated levels of cardiac cathepsin D in starvation, and (c) cathepsin D processing in hearts of fasted animals is incomplete, with accumulation of the precursor during pulse-chase experiments of 6 h duration. Based upon these results, a three-stage model for the regulation of cathepsin D activity in rabbit heart is proposed.

Alterations of myocardial amino acid metabolism in chronic ischemic heart disease.

Arteriovenous differences (A-V) of all naturally occurring amino acids, lactate, and oxygen were measured simultaneously with coronary sinus blood flow (CSBF) in 8 normal subjects and 11 patients with coronary artery disease at rest and during pacing stress. Mean values for CSBF and myocardial oxygen consumptions (MVO2) for the two groups were similar at rest and during pacing, although mean CSBF and MVO2 increased significantly in both groups in the paced as compared to the rest state. Alanine (ala) was the only amino acid released by the myocardium, while only glutamic acid(glu) demonstrated uptake. Mean A-V ala was negative at rest in the control and coronary disease groups (-4.8+/-3.8 vs. -22.0+/-3.0 nmol/ml, respectively), but was significantly more negative in the coronary group (P less than 0.001) and not statistically different than zero in the normals. A-V ala became significantly negative with pacing in the normals (-10.0+/-4.3 nmol/ml), remained unchanged in the coronary group (-23.0+/-2.9 nmol/ml), and was significantly more negative in the coronary group (P less than 0.05). Calculation of data on the basis of net ala flux ([A-V] X [CSBF X hematocrit]) yielded similar results as that obtained with A-V differences. A-V glu was significantly positive in normals (27.7 +/- 8.9 nmol/ml, P less than 0.01) and coronary patients (59.9 +/- 8.9 nmol/ml, P less than 0.01) at rest but significantly greater in the latter group (P less than 0.001). With pacing, A-V glu remained significantly greater than zero in coronary patients (35.3 +/- 6.3 nmol/ml) and decreased to zero in the normals (4.3 +/- 11.8 nmol/ml). Calculation of net glu flux (nmol/min) at rest yielded data similar to that based on A-V difference. With pacing, net glu flux in the coronary patients did not decrease due to the augmentation of CSBF. No relation between A-V glu or ala and CSBF, MVO2 or A-V lactate was noted. The data demonstrate that specific alterations of myocardial amino acid metabolism characterize patients with chronic ischemic heart disease.

Incidence and clinical significance of transient creatine kinase elevations and the diagnosis of non-Q wave myocardial infarction associated with coronary angioplasty.

To assess the incidence and clinical significance of elevated total plasma creatine kinase (CK) and MB isoenzyme fraction after apparently successful coronary angioplasty, a prospective study of 272 consecutive elective procedures was undertaken. Total CK (normal less than 100 IU/liter) and CK MB isoenzyme (normal less than 4%) were measured immediately after successful completion of the procedure and every 6 h for 24 h. All nonelective procedures and results not fulfilling all American Heart Association/American College of Cardiology Task Force guideline criteria for a successful result were excluded from analysis. Of the 272 elective procedures, 249 (92%) were successfully; abnormally elevated CK or CK MB serum levels, or both, were found in 38 (15%) of the successful outcomes. Three patterns of abnormal enzymes were identified: 15 patients with CK greater than or equal to 200 IU/liter and CK MB greater than or equal to 5% (group 1), 4 patients with CK greater than or equal to 200 IU/litter and CK MB less than or equal to 4% (group 2) and 19 patients with CK less than 200 IU/liter and CK MB greater than or equal to 5% (group 3). The three groups were distinguishable by the nature of the complications causing the enzyme release (in particular, the etiology and clinical manifestations). There were significantly more clinically apparent events in group 1 than in the other groups (13 of 15 versus 11 of 23, p less than 0.01) and more events associated with persistent electrocardiographic changes (p = 0.05) and chest pain (p less than 0.05). However, no clinically important sequelae were recognizable in any group at hospital discharge. Thus, abnormal cardiac serum enzyme release after apparently successful coronary angioplasty is 1) relatively common; 2) has many possible causes, including both minor complications and early reversibility of impending major complications; and 3) results in no permanent clinical sequelae.

Prospective study comparing different echocardiographic measurements of pulmonary capillary wedge pressure in patients with organic heart disease other than mitral stenosis.

In 25 patients with cardiac disease, but free of left ventricular inflow obstruction, the electrocardiogram and M-mode echocardiogram of the aortic root, left atrium and both the mitral and the aortic valves were obtained simultaneously with the pulmonary artery wedge pressure (PAWP) during right heart catheterization. The echocardiographic measurements of the left atrial size, PR-AC interval, left atrial emptying index and the ratio between the electrocardiographic Q wave to mitral valve closure (Q-MVC) and between aortic valve closure to the mitral E point (AVC-E) were correlated to the pulmonary artery wedge pressure by means of linear regression analysis. A formula in which PAWP = 36.6 (Q-MVC/AVC-E)-- 2 was prospectively used to study the measured pressure in the current group of patients. The pulmonary artery wedge pressure derived from these latter measurements correlated well with the invasive measurement of this pressure (r = 0.91). The pulmonary artery wedge pressure calculated by echocardiography differed from the pulmonary artery wedge pressure measured by catheterization by 3 mm Hg or less in 19 of the 25 patients, by 4 mm Hg or less in 22 patients and by 6 mm Hg or less in 24 patients. Although the correlation between the (Q-MVC/AVC-E) ratio and measured pulmonary artery wedge pressure was highly significant (r = 0.91, probability [p] less than 0.001, n = 25), the left atrial emptying index, PR-AC and left atrial size revealed poor correlation coefficients (r = 0.45, r = 0.45 and r = 0.56 [p less than 0.05]), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

The tricuspid valve in carcinoid syndrome. An echocardiographic study.

Carcinoid syndrome was diagnosed in a 48-year-old man by urinary 5-hydroxyindoleacetic acid test results and liver biopsy findings. Cardiac catheterization disclosed tricuspid stenosis and mild pulmonic stenosis. The distinctive echocardiographic findings included a tricuspid valve moving in unison with the annulus and thickened immobile tricuspid leaflets. Unlike in rheumatic heart disease, diastolic doming of the tricuspid leaflets was not seen.

A double antibody radioimmunoassay for canine cardiac cathepsin D.

We have developed a sensitive double antibody radioimmunoassay for measuring canine cardiac cathepsin D. Radioiodinated cathepsin D was prepared by chloramine T oxidation using a highly purified source of enzyme. High avidity antiserum to the canine cardiac enzyme was raised in rabbits. Antibody-bound cathepsin D was separated from free enzyme using goat anti-rabbit IgG second antibody. The least amount of immunoreactive enzyme measurable in the radioimmunoassay was 2.4 ng.cm-3 as determined by antibody titration. The assay was linear for concentrations of enzyme in the range of 10 to 120 ng.cm-3. Within-assay and between-assay variations were 12%. The radioimmunoassay described was used to measure the immunoreactive cathepsin D content of the 100 000 x g supernatant fraction of canine myocardial homogenates.

Sudden death associated with thyroid hormone abuse.

Three patients with hyperthyroidism due to deliberate intake of excessive amounts of L-thyroxine are described wherein death was "instantaneous" and presumably due to ventricular fibrillation. Hyperthyroidism was not recognized on admission in two of these patients because of atypical presentations. Autopsy was performed in two patients. In one patient no coronary disease was present and focal myocarditis with leukocytic infiltration was noted. The second patient had an acute posterior myocardial infarction due to acute coronary thrombosis, but focal areas of leukocytic infiltration and fibrosis were also seen in the anterior wall not involved in the process of infarction. Factitious hyperthyroidism due to L-thyroxine abuse can be associated with sudden death in the absence of coronary artery disease and may be related to a drug induced myocarditis.

Balancing service and education: improving internal medicine residencies in the managed care era.

BACKGROUND: Internal medicine training programs must adapt to health care systems faced with balancing the competitive priorities of patient-care responsibilities and educational needs. OBJECTIVE: To evaluated the effects of a major organizational change on the inpatient service of an internal medicine residency program in a vertically integrated health system. METHODS: We changed the structure of our program from a system in which the hospitalized patients' primary physicians were responsible for daily inpatient management, while teaching was assigned to a defined teaching rounder, to a method in which the rounding attending was responsible for both teaching and patient care. Measurements before and after the change in the rounding system included: the McGill University clinical tutor evaluations, time-motion observations of house staff, patient satisfaction surveys, average length of stay data, and physician focus groups to assess physician satisfaction. RESULTS: The rounding attendings consistently received excellent to superior ratings by the house staff both before and after the implemented change. Compared to time-motion observations performed before the change, observations recorded after the change suggested that a greater percent of house staff time was spent on educational activities. The responses of patient satisfaction surveys indicated that the perception of quality of care remained high after the system change. Lastly, the average length of stay for patients on the general internal medicine and subspecialty services was reduced from 7.6 days before the change to 6.6 days after the change, a difference of 0.92 day (95% confidence interval 1.3 to 0.6, P < 0.001). CONCLUSIONS: Through organizational restructuring, it is possible to improve the quality of patient care and improving the efficiency of patient-care management.

Inhibition of E-selectin-, ICAM-1-, and VCAM-1-mediated cell adhesion by benzo[b]thiophene-, benzofuran-, indole-, and naphthalene-2-carboxamides: identification of PD 144795 as an antiinflammatory agent.

It was previously reported that 3-alkoxybenzo[b]thiophene-2-carboxamides exemplified by 1, 5-methoxy-3-(1-methylethoxy)benzo[b]thiophene-2-carboxamide, decreased the adherence of neutrophils to activated endothelial cells by inhibiting the upregulation of the adhesion molecules E-selectin and ICAM-1 on the surface of the endothelium. This finding is extended here to a series of 3-thiobenzo[b]thiophene-2-carboxamides and also heterocyclic analogs of 1, including benzofurans, indoles, and napthalenes. The compounds that inhibited the expression of E-selectin and ICAM-1 had the same effect on the expression of VCAM-1. PD 144795, 5-methoxy-3-(1-methylethoxy)benzo[b]thiophene-2-carboxamide 1-oxide (44), the sulfoxide analog of 1, was orally active in several models of inflammation. The in vitro and in vivo activity of PD 144795 resided predominately in the S-enantiomer.

Inotropic agents and infarct size. Theoretical and practical considerations.

Recent data demonstrating the ability of interventions that alter the balance between myocardial oxygen demand and supply to affect infarct size are reviewed. The effects of inotropic agents on the determinants of myocardial oxygen consumption and coronary blood flow are discussed relative to the potential of these drugs to decrease or increase infarct size in the experimental animal and in man. The applicability of the animal data to the clinical situation is discussed and, on the basis of these considerations, guidelines are presented for the use of inotropic agents in patients with acute myocardial infarction.

Myocardial scintigraphy with technetrium-99m pyrophosphate during the early phase of acute infarction.

To determine the sensitivity of myocardial scintigraphy with technetium-99m pyrophosphate during the early phase of acute myocardial infarction, 31 patients admitted to the coronary care unit with prolonged ischemic pain underwent imaging within 4 to 8 hours and again at 24 hours after the onset of symptoms. In 11 of 15 patients with documented acute myocardial infarction, increased focal myocardial uptake was demonstrated on early myocardial scintigraphy. Focal uptake was observed in only 2 of 16 patients with unstable angina pectoris. Three or four patients with normal early scintigrams had massive transmural myocardial infarction. Normal early scintigrams in these three patients may have reflected poor perfusion because the images were abnormal at 24 hours. In four patients the extent of technetium-99m pyrophosphate uptake increased more than 20 percent at 24 hours without other evidence of infarct extension. In the other seven patients, there was no significant change in the area of the abnormal radioactive uptake between early and delayed scintiscans. This study suggests that technetium-99m pyrophosphate scintigraphy can defect acute myocardial infarction as early as 4 hours after the onset of symptoms although the sensitivity rate (73 percent) is less than that at 24 hours.

Correlation of acute myocardial infarct scintigraphy with postmortem studies.

Acute myocardial infarct scintigraphy with technetium-99m-pyrophosphate was performed in a patient with an acute massive transmural infarct. The patient died 12 hours later, and postmortem tracer studies demonstrated a tracer concentration ratio of 13:1 between acutely infarcted myocardium and normal myocardium remote from the infarct. The concentration of tracer in tissue bordering on the infarct but without histologic evidence of acute infarction was 1.5 times that in normal tissue remote from the infarct. In vitro scintigraphy of the excised heart revealed a pattern of tracer distribution similar to that of scintiscans obtained before death. The biologic distribution of 99mTc-pyrophosphate, with large tracer concentrations only within the acutely infarcted tissue, suggests that acute myocardial infarct scintigraphy can be used to estimate the extent of an acute myocardial infarct.

Acquired cyanotic heart disease secondary to traumatic tricuspid regurgitation. Case report with a review of the literature.

A case of traumatic tricuspid insufficiency leading to right atrial enlargement and to a patent foramen ovale with right to left shunting is presented. Six similar cases previously reported are reviewed. The time course of clinical deterioration was related to the type of tricuspid valve damage incurred. Papillary muscle rupture led to surgery within a year, whereas less severe chordal damage allowed a more benign course that lasted from 10 to 25 years from the time of injury to the time of surgery. Surgical repair of the incompetent tricuspid valve and closure of the atrial septal defect led to significant improvement. The diagnostic usefulness of radionuclide imaging and echocardiography is demonstrated in this case. A mechanism of right to left interatrial shunting in the presence of normal pulmonary arterial pressures is proposed; this invokes phasic increases in right atrial pressure from tricuspid insufficiency and streaming of blood from the inferior vena cava into the left atrium across a patent foramen ovale in a manner that resembles conditions in the fetal circulation.

Natural history of S-T segment elevation after acute myocardial infarction.

Clinical, electrocardiographic and cineventriculographic data in two patient groups were analyzed to define the natural history of S-T segment elevation after myocardial infarction. In sixteen of 22 patients (73 percent) with acute inferior myocardial infarction, S-T segment elevation was present on hospital admission, persisting in 1 (5 percent) by the 2nd week. S-T segment elevation was present on admission in 18 of 23 patients (78 per cent) with acute anterior myocardial infarction and persisted in 13 after 1 week and in 9 of 14 (64 percent) during a follow-up period of 1 to 6 months. S-T segment elevation lasting more than 2 weeks after myocardial infarction did not resolve. Compared with patients with inferior myocardial infarction or anterior infarction without persistent S-T segment elevation, patients with anterior infarction and persistent S-T segment elevation had a higher level of mean maximal serum creatine phosphokinase (CPK), more severe left ventricular decompensation and a greater frequency of death in the early follow-up period. In a separate series of 95 patients with cineangiographically documented coronary artery disease, 40 of 65 patients (62 percent) with advanced anterior and apical asynergy had persistent S-T segment elevation. By contrast, only 1 of 30 (3 percent) with coronary disease and normal ventriculograms had persistent S-T segment elevation. We concluded that (1) the natural history of S-T segment elevation after myocardial infarction is resolution within 2 weeks in 95 percent of inferior but in only 40 percent of anterior infarctions; (2) S-T segment elevation persisting more than 2 weeks after myocardial infarction does not resolve; (3) persistent S-T segment elevation is associated with clinically more severe myocardial infarction; and (4) in patients with coronary artery disease, persistent S-T segment elevation after myocardial infarction is a specific but insensitive index of advanced asynergy.

Alteration of left ventricular performance by left bundle branch block simulated with atrioventricular sequential pacing.

The effects of atrioventricular (AV) sequential pacing-induced left bundle branch block (LBBB) on left ventricular (LV) performance were evaluated during cardiac catheterization in 9 randomly selected patients being investigated for chest pain. All patients were in normal sinus rhythm with a normal P-R interval and QRS duration. LV performance was assessed by both hemodynamic and angiographic measurements. The maximal rate of LV pressure increase (dP/dt), rate of maximal LV pressure decrease (-dP/dt), LV end-diastolic pressure (LVEDP), end-diastolic volume (LVEDV), end-systolic volume (LVESV), stroke volume and percent ejection (EF) were measured during right atrial and AV sequential pacing at a constant pacing rate. The average pacing rate was 97 +/- 3 beats/min (mean +/- standard error of the mean). In each patient, both dP/dt and -dP/dt decreased significantly (p less than 0.001) during AV sequential pacing compared with atrial pacing at the same rate, from 1,541 +/- 68 to 1,319 +/- 56 mm Hg/s for dP/dt and from 1,506 +/- 86 to 1,276 +/- 92 for -dP/dt. LVEDP did not change significantly when atrial (17 +/- 3 mm Hg) and AV sequential pacing (16 +/- 2 mm Hg) were compared. Mean LVEDV did not change during atrial (135 +/- 13 ml) or AV sequential pacing (137 +/- 14 ml). In contrast, the LVESV during AV sequential pacing was higher by 15 ml (23%) (from 48 +/- 10 to 63 +/- 12 ml) (p less than 0.001); as a result, the stroke volume was lower by 13 ml (15%) and the EF decreased by 10%, from 66 to 56% (-15%).(ABSTRACT TRUNCATED AT 250 WORDS)

Balloon dilatation of symptomatic subacute intimal dissection presenting as restenosis.

Repeat percutaneous transluminal coronary angioplasty (PTCA) for subacute intimal dissections that produce symptoms after a period of 1 month or more is reluctantly performed for fear of extension and abrupt closure. Patients were identified with demonstrated intimal dissections (intimal contrast staining or frank intimal flap) at the time of initial PTCA who returned a mean of 17.5 weeks (range 9 to 50) later with recurrent chest pain. Repeat angiography revealed luminal compromise due to dissection rather than restenosis in 22 patients. Of these, 17 underwent repeat PTCA. Elective bypass surgery without attempted PTCA was chosen in the other 5 patients because of extensive intimal dissections (greater than 2 balloon lengths) or involvement of critical branches. In the group of 17 patients who had repeat PTCA, 10 (group 1) had a frank intimal flap without persistent contrast staining after the initial PTCA, while 7 (group 2) had both persistent staining and a flap. Successful PTCA was performed in 13 of these 17 patients (76%). There were 2 abrupt closures and 2 unsatisfactory luminal openings. One of these patients required urgent coronary bypass surgery. All 10 group 1 patients had successful repeat procedures versus only 3 of 7 group 2 patients (p = 0.01). The 3 patients with the greatest degree of luminal compromise immediately after the initial PTCA had failed repeat PTCA attempts. These results suggest that repeat PTCA for subacute intimal dissections presenting as restenosis can be successfully performed in selected patients, and that the presence of contrast staining and the degree of luminal compromise by the dissection may be predictive of outcome.

Intravenous nitroglycerin for the treatment of angina at rest unresponsive to standard nitrate therapy.

Thirty-five patients who had angina at rest that was unresponsive to standard therapy comprised of oral or topical nitrates and beta-blocking drugs were treated with a continuous infusion of intravenous nitroglycerin (IVNTG). The infusion was started at 10 micrograms/min and increased by 10 micrograms/min increments every 5 minutes until an infusion rate of 50 micrograms/min was reached. After each episode of rest angina, the infusion was increased by 50 micrograms/min in the same stepwise manner. Data from a 24-hour baseline control period were compared with those from a 24-hour IVNTG endpoint period at which time the highest IVNTG infusion rate was administered. The average IVNTG infusion rate was 140 +/- 15 micrograms/min. With IVNTG therapy, the number of episodes of angina at rest decreased from 3.5 +/- 0.4 to 0.3 +/- 0.1, sublingual nitroglycerin use decreased from 1.9 +/- 0.3 to 0.4 +/- 0.1 mg/day, and morphine sulfate administration decreased from 5.5 +/- 1.3 to 0.4 +/- 0.2 mg/day (all p less than 0.001). When each patient's response on the endpoint day was analyzed, 25 were defined as complete (no rest angina), 8 as partial (greater than 50% decrease in the number of episodes/day from control values), and 2 as nonresponders. No significant drug-induced adverse effects occurred. IVNTG appears to be effective therapy for angina at rest refractory to standard oral and topical medications.