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Biomedical subjects

G Johnson

Publications and source records attributed to G Johnson.

At least 271 records · Page 15Linked to original sources
PubMed1993

Femorofemoral bypass graft: analysis of patency and factors influencing long-term outcome.

PURPOSE: To evaluate the results of femorofemoral bypass graft (FFBPG), we analyzed 110 consecutive FFBPGs performed at our institution during an 11-year period. METHODS: In 62 (56%) patients the indication for surgery was claudication and in 48 (44%) patients rest pain or tissue loss. In 42 patients the superficial femoral artery (SFA) was occluded. A preoperative percutaneous transluminal balloon angioplasty (PTA) was performed in 24 (22%) patients to correct a significant donor iliac artery stenosis. In 48 (44%) patients a total of 54 arterial procedures were performed simultaneously with FFBPG. RESULTS: After surgery 75 (68%) patients were moderately or markedly improved, whereas 20 (18%) were minimally improved, unchanged, or worse, including 7 (6%) with hemodynamic failures. The in-hospital mortality rate was 4.5%. Actuarial patient survival rate was 70% +/- 8.6% at 6 years. The actuarial primary graft patency rate was 83% +/- 4.2% at 1 year, 71% +/- 6.9% at 3 years, 60% +/- 8.3% at 5 years, and 51% +/- 9.6% at 6 years. Age, sex, and race of the patient did not influence graft patency. Grafts placed for limb-threatening ischemia or in patients with SFA occlusion had a similar patency rate compared with those placed for claudication or in patients with patient SFA. The overall limb preservation rate was 83% +/- 7.3% at 5 years but was only 64% for patients who underwent operation for limb-threatening ischemia. CONCLUSIONS: In conclusion, FFBPG offers moderately low long-term patency in a population with limited survival. Outflow procedures performed concomitantly with FFBPG seemed to compensate for the negative impact on graft patency rate of ipsilateral SFA occlusion and limb-threatening ischemia. Limb-threatening ischemia, however, carried a significantly higher (p < 0.05) amputation rate. The influence of preoperative donor iliac artery percutaneous transluminal balloon angioplasty on FFBPG patency remains unclear.

Adolescent↗
PubMed1993

Early myocardial clearance kinetics of technetium-99m-teboroxime differentiate normal and flow-restricted canine myocardium at rest.

Technetium-99m-teboroxime (CardioTec) is a promising new myocardial perfusion imaging agent. The purposes of this study were to define teboroxime clearance kinetics in normal and flow-restricted myocardium over a 1-hr period and to determine whether teboroxime kinetics are useful in detecting myocardial hyperperfusion. Accordingly, the circumflex arteries of 23 dogs were stenosed. By using miniature cadmium-telluride radiation detectors, myocardial teboroxime activities were continuously monitored in both the control and the stenosed zones. Myocardial clearance of teboroxime was modeled and found to be biexponential over 1 hr. A significant difference in myocardial clearance between the normal and stenosed zones (t1/2 = 4.5 +/- 0.9 min versus 10.2 +/- 2.6 min, respectively; p < 0.05) was observed for the first exponential phase (the first 5 min following initial uptake), but not for the second exponential phase (t1/2 = 160.7 +/- 35.9 min versus 140.4 +/- 27.4 min, respectively; p = ns). One hour fractional teboroxime blood clearance was 0.95 +/- 0.03, with most of the clearance occurring during the first 4 min. Gamma camera images of excellent quality demonstrated an initial defect with significant quantitative differential clearance over 1 hr. Thus, there are two phases of myocardial teboroxime clearance. During the early exponential clearance phase, teboroxime kinetics at rest may be able to differentiate between normal and hypoperfused myocardium.

Animals↗
PubMed1993

Influence of age on mechanisms and prognosis of heart failure. The V-HeFT VA Cooperative Studies Group.

BACKGROUND: Advanced age is commonly thought to carry a poor prognosis in congestive heart failure, but the case has not been established. The Department of Veterans Affairs Cooperative Vasodilator-Heart Failure Trials (V-HeFT I and II) provided a large data base to assess the effect of age on hemodynamic profiles and survival in the failing heart. METHODS AND RESULTS: Patients were stratified into four categories according to age: < or = 55, 56-60, 61-65, and > 65 years. The distributions of treatments and baseline characteristics from history, physical findings, and laboratory data were analyzed for differences across age categories. Survival curves were calculated for age strata according to treatment, presence or absence of coronary artery disease, ejection fraction, and peak oxygen consumption. Risk ratios for age and treatment categories showed no consistent trend of treatment effect on mortality. Age was significantly associated with coronary artery disease, hypertension, rhythm disturbances, systolic blood pressure, ejection fraction, and peak oxygen uptake, but successive age strata did not show incremental changes. Survival curves did not show progressively steeper slopes with advancing age. In V-HeFT I, the oldest patients did have the poorest survival, but age interacted with the presence of coronary artery disease and randomization into the placebo group. CONCLUSIONS: Contrary to intuitive thinking, age alone did not shorten the survival in congestive heart failure patients who were < 75 years old and receiving optimal therapy.

Age Factors↗
PubMed1993

Prognostic significance of serial changes in left ventricular ejection fraction in patients with congestive heart failure. The V-HeFT VA Cooperative Studies Group.

BACKGROUND: In congestive heart failure patients, a single measurement of left ventricular ejection fraction (LVEF) provides important prognostic information. The importance, if any, of improvement or worsening in serial LVEF has not been defined. The Department of Veterans Affairs Cooperative Vasodilator-Heart Failure Trials (V-HeFT) data base was analyzed to determine the prognostic importance of LVEF changes. METHODS AND RESULTS: The data bases for V-HeFT I (n = 642) and V-HeFT II (n = 804) were analyzed. All patients had heart failure with documented exercise intolerance and abnormal LVEF or cardiac dilatation by chest x-ray or echocardiography. Radionuclide LVEF was obtained at baseline, within 6 months, and at least yearly after randomization to treatment. Cumulative survival subsequent to LVEF follow-up measurements was calculated for strata defined by LVEF change from baseline. In V-HeFT I, patients treated with hydralazine/isosorbide dinitrate (H-I) experienced a significant (p < 0.001) increase in LVEF and a survival advantage over those treated with placebo and prazosin. In V-HeFT II, both treatment groups showed significant improvements in LVEF, with the increase with H-I greater than that with enalapril, and enalapril provided a significant survival advantage over H-I. Change (> 5) in LVEF from baseline at 6 months (V-HeFT I) and 1 year (V-HeFT II) were the strongest predictors of mortality among the serial measurements and were significant after adjustment for therapy and baseline LVEF. Baseline clinical variables were not helpful in predicting the patients who would experience an improvement in LVEF. CONCLUSIONS: In patients with heart failure, serial measurements of LVEF provide additional important prognostic information. Vasodilator therapy with H-I is associated with an improvement in LVEF and prognosis. Vasodilator therapy with enalapril improves LVEF less than H-I but provides an additional survival benefit.

Drug Therapy, Combination↗
PubMed1993

Mechanism of death in heart failure. The Vasodilator-Heart Failure Trials. The V-HeFT VA Cooperative Studies Group.

BACKGROUND: The Vasodilator-Heart Failure Trial (V-HeFT) data base provides information on the mechanism of death of male veterans entered into two trials that evaluated the effect of vasodilator therapy on survival in heart failure. METHODS AND RESULTS: Men aged 18-75 years with heart failure were recruited at 13 Department of Veterans Affairs Medical Centers. In V-HeFT I, 283 of 642 patients (44%) died during follow-up (average, 2.3 years), and in V-HeFT II, 285 of 804 randomized patients (35.5%) died during follow-up (average, 2.5 years). Mechanism of death was established centrally using a standardized classification. In V-HeFT I, 124 of the 283 deaths (43.8%) were sudden with no worsening of symptoms; in V-HeFT II, 104 of the 285 deaths (36.5%) were sudden. An average of 31.5% of the deaths (31.4% and 31.6%, respectively) in the two trials was due to pump failure. The proportion of sudden deaths that occurred without worsening of symptoms was similar in patients with and without ischemic heart failure. Sudden deaths tended to occur earlier and pump failure deaths later in both V-HeFT studies. There was a trend for a lower percentage of cardiac deaths from pump failure and a higher percentage from sudden death in subgroups with higher peak exercise oxygen consumption (VO2), higher ejection fraction, and lower plasma norepinephrine levels. The proportion of deaths that occurred suddenly was similar in placebo, prazosin, and hydralazine plus isosorbide dinitrate treatment groups but was significantly lower in the enalapril treatment group. In V-HeFT I, measures of cardiac function and VO2 predicted pump failure death and sudden death. In V-HeFT II, VO2 and cardiothoracic ratio were independent predictors of all-cause deaths and pump failure deaths; only ejection fraction was an independent predictor of both pump failure and sudden death. CONCLUSION: Although mechanistically distinct terminal events can be identified in patients with heart failure and physiological measurements can provide some insight into the risk of these disparate events, sudden death and pump failure death both appear largely to be linked to the severity of cardiac dysfunction and symptoms. Strategies to identify individuals for selective preventive therapy are not yet practical.

Cause of Death↗
PubMed1993

Influence of prerandomization (baseline) variables on mortality and on the reduction of mortality by enalapril. Veterans Affairs Cooperative Study on Vasodilator Therapy of Heart Failure (V-HeFT II). V-HeFT VA Cooperative Studies Group.

BACKGROUND: The effects of hydralazine plus isosorbide dinitrate were compared with those of enalapril in 804 men receiving digoxin and diuretic therapy for chronic congestive heart failure (CHF) in the Department of Veterans Affairs Cooperative Vasodilator-Heart Failure Trial (V-HeFT II). METHODS AND RESULTS: Patients were randomly assigned to receive 20 mg of enalapril or 300 mg of hydralazine plus 160 mg of isosorbide dinitrate daily. At 2 years, treatment with enalapril resulted in a significant (28%) reduction in mortality relative to the active control treatment. Baseline variables were examined to determine their impact on risk of mortality and on relative response to treatment. Mortality rates were significantly higher in patients with severe ventricular arrhythmias; in patients with low baseline ejection fractions, low peak oxygen consumption, and low systolic blood pressures; in patients with high cardiothoracic ratios, high scores indicating greater impairment on a quality-of-life questionnaire, and high plasma norepinephrine or renin levels; and in patients in New York Heart Association (NYHA) classes III and IV. Coronary artery disease, duration of CHF, and patient age were not predictive of mortality. Enalapril reduced mortality significantly compared with hydralazine/isosorbide dinitrate in patient subgroups with high plasma renin or norepinephrine levels and in patients with low cardiothoracic ratios. Furthermore, enalapril conferred significantly greater protection from mortality than hydralazine/isosorbide dinitrate in patients in NYHA classes I and II and in patients without arrhythmias or with < or = 10 premature ventricular contractions per hour. CONCLUSIONS: Of the prerandomization characteristics that were predictive of mortality in patients with CHF, only neurohormone measurements, cardiothoracic ratios, arrhythmia severity, and NYHA class identified subgroups of patients who benefited most from treatment with enalapril; a treatment interaction across strata was detected only for plasma norepinephrine and NYHA class. In no patient subgroup was the mortality with enalapril treatment significantly higher than the mortality with hydralazine/isosorbide dinitrate treatment.

Drug Therapy, Combination↗
PubMed1993

Plasma norepinephrine, plasma renin activity, and congestive heart failure. Relations to survival and the effects of therapy in V-HeFT II. The V-HeFT VA Cooperative Studies Group.

BACKGROUND: Congestive heart failure is a clinical syndrome characterized by neuroendocrine activation. Measurements of plasma norepinephrine and plasma renin activity were performed in the Vasodilator-Heart Failure Trial II (V-HeFT II) to characterize the effect of therapy on neuroendocrine activation and to examine the responses to therapy among patients with different degrees of activation. METHODS AND RESULTS: The baseline median plasma norepinephrine value (n = 743) was 490 pg/mL and the baseline median plasma renin activity (n = 737) was 6.9 ng.mL-1 x hr-1. Baseline plasma renin activity and plasma norepinephrine correlated poorly with each other (r = 0.12), implying that these two neuroendocrine systems are being activated by separate processes. By univariate analysis, the logarithms of the plasma norepinephrine (p < 0.0001) and the plasma renin activity (p = 0.01) were significantly related to all-cause mortality. In a multivariate analysis that included other significant univariate prognostic variables (i.e., baseline ejection fraction, peak oxygen consumption during exercise, and cardiothoracic ratio), log plasma norepinephrine but not plasma renin activity remained a significant (p = 0.02) predictor of mortality. Baseline plasma norepinephrine correlated poorly with baseline left ventricular ejection fraction (r = -0.18), peak oxygen consumption (r = -0.15), and cardiothoracic ratio (r = 0.11). Neither the plasma norepinephrine (r = 0.09) nor the plasma renin activity (r = 0.18) was closely associated with a quality of life assessment at baseline. The baseline plasma norepinephrine level in patients randomized to enalapril (mean, 593 +/- 388 [SD] pg/mL; n = 372) and to hydralazine and isosorbide dinitrate (mean, 544 +/- 297 pg/mL; n = 371) were similar. Thirteen weeks after randomization, plasma norepinephrine did not change (-5 +/- 393 pg/mL) in 312 patients randomized to enalapril but increased significantly by 74 +/- 311 pg/mL (p < 0.0001) in 300 patients assigned to hydralazine-isosorbide dinitrate. The plasma norepinephrine increased significantly more in patients assigned to hydralazine-isosorbide dinitrate than those on enalapril at both 13 weeks (p = 0.01) and at 1 year (p = 0.04) (90 +/- 302 pg/mL [n = 240] versus 14 +/- 376 pg/mL [n = 265]). Based on previous reports and examination of survival among several plasma norepinephrine strata, the baseline plasma norepinephrine data were grouped into three relatively homogeneous strata for further analysis. The cumulative mortality was significantly different between the three strata (p < 0.0001). The patients with plasma norepinephrine > 900 pg/mL had a higher mortality than those with corresponding values from 601 to 900 pg/mL or < 600 pg/mL. The survival benefit of enalapril compared with hydralazine-isosorbide dinitrate was most evident in those patients with a plasma norepinephrine value > 900 pg/mL. Although the plasma renin activity was not strongly associated with survival, patients in the upper quartile (> 16 ng.mL-1 x hr-1) had the worst prognosis. Among this group, the patients on enalapril demonstrated significantly better survival than those on hydralazine-isosorbide dinitrate (p = 0.02). CONCLUSIONS: This study confirms that plasma norepinephrine is an independent predictor of prognosis in patients with congestive heart failure. Hydralazine-isosorbide dinitrate treatment, unlike enalapril treatment, was associated with increased plasma norepinephrine concentration during the first year of follow-up. The enalapril group had a significantly lower mortality, and this survival benefit of enalapril as compared with hydralazine-isosorbide dinitrate was most evident among patients with the most marked neuroendocrine activation. Neuroendocrine activation is an important prognostic factor for patients with congestive heart failure and is an important determinant of the differential response to vasodilators.

Drug Therapy, Combination↗
PubMed1993

Enalapril decreases prevalence of ventricular tachycardia in patients with chronic congestive heart failure. The V-HeFT II VA Cooperative Studies Group.

BACKGROUND: Patients with heart failure have a high prevalence of serious arrhythmias and sudden cardiac-death. METHODS AND RESULTS: Male patients aged 18-75 years with chronic heart failure were randomized to enalapril or hydralazine-isosorbide dinitrate. Short-term (4-hour to 8-hour) Holter tape recordings were performed before randomization, at 3 months, at 1 year, and yearly thereafter. Of 804 patients randomized to therapy, 715 had Holters at baseline. Couplets were noted in 56% versus 60% and ventricular tachycardia (VT) (three or more consecutive ventricular premature beats) in 27% versus 29% of patients randomized to enalapril versus hydralazine-isosorbide dinitrate, respectively. The presence of VT at 3 months, 1 year, and 2 years predicted significantly higher mortality during the subsequent year (p < 0.0001, p < 0.001, and p < 0.037, respectively). In the enalapril group, VT prevalence decreased by 27% at 1 year (p < 0.02). A decrease in prevalence of VT was not seen in the hydralazine-isosorbide dinitrate group. New VT was seen in 11% of enalapril patients versus 24% of hydralazine-isosorbide dinitrate patients at 1 year (p < 0.002). When compared with hydralazine-isosorbide dinitrate at 1 and 2 years, there was a 52% and 49% reduction, respectively, in sudden deaths in the enalapril group. Thus, at 1 and 2 years, the decrease in sudden deaths in the enalapril group coincided with the decrease in VT prevalence and the decrease in new VT emergence. CONCLUSIONS: In patients with heart failure, VT and couplets predict increased mortality. When compared with hydralazine-isosorbide dinitrate, enalapril decreases both the persistence of baseline VT at 3 months and the emergence of new VT at 1 and 2 years. The reduction in VT prevalence parallels a reduction in sudden death. The effect of enalapril on survival over hydralazine-isosorbide dinitrate may be related to its ability to reduce prevalence of ventricular arrhythmia.

Death, Sudden, Cardiac↗
PubMed1993

Hydralazine and isosorbide dinitrate combination improves exercise tolerance in heart failure. Results from V-HeFT I and V-HeFT II. The V-HeFT VA Cooperative Studies Group.

BACKGROUND: To better define the effects of long-term vasodilator therapy on exercise performance in chronic congestive heart failure, we compared placebo with prazosin and with the combination of hydralazine and isosorbide dinitrate (Hyd-Iso) in 642 men over a 5-year period in V-HeFT I. METHODS AND RESULTS: Patients were randomized (double-blind) to 20 mg of prazosin daily or 300 mg of hydralazine plus 160 mg daily of isosorbide dinitrate or placebo. We compared enalapril (20 mg daily), a converting enzyme inhibitor, with Hyd-Iso in 804 men over another 5-year period in V-HeFT II: Background therapy in both trials consisted of digitalis and diuretics. Serial bicycle ergometric exercise was performed with gas exchange measurements during progressive incremental work rates to a symptom-limited peak end point. Gas exchange anaerobic threshold (ATge) measurement was performed in the second trial. In V-HeFT I, an increase in peak VO2 with Hyd-Iso compared with placebo approached significance at 2 months (p < 0.16) and was significant (p < 0.04) at 1 year. In V-HeFT II, Hyd-Iso significantly increased peak VO2 compared with enalapril (p < 0.01 at 3 months, p < 0.02 at 6 months and 2 years). The changes in ATge measurements were not statistically different between the two treatment groups in V-HeFT II: CONCLUSIONS: Combination therapy with Hyd-Iso was more effective in increasing peak VO2 than placebo, prazosin, or enalapril in patients with mild-to-moderate congestive heart failure. Long-term data were confounded by mortality and other events, which may have led to an underestimate of the benefits of Hyd-Iso over placebo and an underestimate of the long-term benefits of enalapril on exercise performance. Therefore, short-term improvement in exercise performance is a suitable therapeutic end point, but long-term studies should more appropriately assess mortality.

Anaerobic Threshold↗
PubMed1993

Echocardiographic variables as prognostic indicators and therapeutic monitors in chronic congestive heart failure. Veterans Affairs cooperative studies V-HeFT I and II. V-HeFT VA Cooperative Studies Group.

BACKGROUND: Echocardiographic indexes of ventricular function have become indispensable in clinical cardiology but have not been tested as prognostic markers or therapeutic monitors in clinical trials. In two Veterans Administration trials on heart failure (Vasodilator-Heart Failure Trials I and II, V-HeFT I and II), echocardiographic variables were analyzed as predictors and monitors and were compared with other indicators of cardiac performance. METHODS AND RESULTS: Echocardiograms were recorded before randomization and at follow-up intervals. Baseline measurements of left ventricular internal diameters (LVIDd, LVIDs), wall thickness (THd, THs), radius to thickness ratios (Rd/THd, Rs/THs), and mitral E-point septal separation (EPSS) were evaluated as predictors of mortality individually, in multivariate regression models with each other, and with nonechocardiographic predictors. Within-subject changes were compared between treatment groups. Cumulative survival curves were compared between strata formed by cut-points of EPSS and Rs/THs data. In Cox regression analyses, EPSS, LVIDs, and Rs/THs were significant predictors of mortality. In V-HeFT I, Rd/THd was a predictor in the presence of ejection fraction and peak oxygen uptake. In patients with EPSS > or = 21, there was an 83% increase in mortality in the subgroup of patients with Rs/THs > or = 2.5 compared with Rs/THs < 2.5 (p = 0.003), whereas there was no statistical difference for EPSS < 21. EPSS showed improvement in patients treated with hydralazine-isosorbide dinitrate compared with placebo at 2 and 18 months and a trend toward deterioration between 36 and 66 months. In V-HeFT II, there were no differences between enalapril and hydralazine-isosorbide dinitrate groups at follow-up. CONCLUSIONS: Echocardiographic variables, EPSS, LVIDs, and Rs/THs were shown to be predictors of mortality and monitors of treatment for heart failure in clinical trials.

Drug Therapy, Combination↗
PubMed1993

Evaluation by patients with heart failure of the effects of enalapril compared with hydralazine plus isosorbide dinitrate on quality of life. V-HeFT II. The V-HeFT VA Cooperative Studies Group.

BACKGROUND: Two new questionnaires concerning the quality of life of patients with heart failure were used in a randomized, controlled trial to determine if the patients' perceptions of the effects of enalapril on their daily activities and sense of well-being were different from those of a group treated with hydralazine and isosorbide dinitrate. METHODS AND RESULTS: The questionnaires were completed at baseline and at 3 months, 6 months, and subsequently every 6 months during follow-up, which averaged 2.5 years (range, 0.5-5.7 years). Data from the questionnaires were reliable as indicated by correlation coefficients between repeated baseline scores of 0.88 and 0.87. Both treatment groups showed a progressive deterioration in quality of life as measured by both questionnaires. The questionnaire scores of the two treatment groups were not significantly different at any follow-up visit. Furthermore, there were no differences between treatments among subgroups defined by baseline questionnaire scores, peak oxygen consumption, ejection fraction, previous vasodilator use, and plasma norepinephrine concentration. CONCLUSIONS: Although several factors may limit the generalization of these results, the lack of a difference with regard to patients' quality of life is an important consideration for the evaluation of the relative therapeutic efficacy of these vasodilators.

Attitude to Health↗
PubMed1993

Effect of enalapril, hydralazine plus isosorbide dinitrate, and prazosin on hospitalization in patients with chronic congestive heart failure. The V-HeFT VA Cooperative Studies Group.

BACKGROUND: Hospitalization of persons with congestive heart failure for recurrent heart failure or other complications is common. METHODS AND RESULTS: Male patients aged 18-75 with chronic heart failure were randomized in two sequential trials designed to study the efficacy of vasodilator therapy. Patients were evaluated every 3 months, and information regarding hospitalizations between visits was obtained from the patient, his family, and/or hospital records. Hospitalization data also were obtained for patients who had died between scheduled clinic visits. Hospitalizations were not recorded if a patient died during transit to the hospital or in the hospital emergency department before admission. In Vasodilator-Heart Failure Trial (V-HeFT) I, no significant difference in number of patients hospitalized or number of hospitalizations was noted among the treatment groups, although there was a trend for fewer and delayed cardiac hospitalizations in the hydralazine plus isosorbide dinitrate arm in which the survival was greater. In V-HeFT II, no difference in hospitalizations was apparent between the enalapril and hydralazine plus isosorbide dinitrate arms. Univariate predictors of hospitalization for all causes were reduced peak oxygen consumption (VO2) during exercise (p < 0.0001), reduced exercise duration (p < 0.0001), increased cardiothoracic ratio on chest radiograph (p < 0.0001), increased age (p < 0.03), and use of antiarrhythmic drugs (p < 0.013), whereas multivariate predictors were reduced peak VO2 (p < 0.0001), use of antiarrhythmic drugs (p < 0.015), and increased cardiothoracic ratio (p < 0.03). Univariate predictors of hospitalization for heart failure were peak VO2 (p < 0.0001), LVEF (p < 0.0001), reduced exercise duration (p < 0.0001), elevated cardiothoracic ratio (p < 0.0001), and elevated plasma norepinephrine (p < 0.0001). Multivariate predictors were exercise duration (p < 0.0001), LVEF (p < 0.04), elevated cardiothoracic ratio (p < 0.03), plasma norepinephrine (p < 0.0005), and coronary artery disease (p < 0.02). Time to first hospitalization, cause specific or overall, was considerably shorter for patients with baseline peak VO2 < 10 mL.kg-1 x min-1 compared with those with peak VO2 > 15 mL.kg-1 x min-1. CONCLUSIONS: Despite better survival in patients randomized to hydralazine plus isosorbide dinitrate compared with placebo and better survival in patients randomized to enalapril compared with hydralazine plus isosorbide dinitrate, no significant differences between the treatment groups were apparent in the incidence of hospitalization or time to first hospitalization for congestive heart failure, for cardiac reasons other than congestive heart failure, or for other causes. V-HeFT I and V-HeFT II data demonstrate no treatment effect on hospitalization, perhaps reflecting in part the effectiveness of the Veterans Affairs special heart failure clinics in dealing with worsening heart failure on an outpatient basis. Identification of predictors of hospitalization were similar in both studies.

Drug Therapy, Combination↗
PubMed1993

Functional capacity in heart failure. Comparison of methods for assessment and their relation to other indexes of heart failure. The V-HeFT VA Cooperative Studies Group.

BACKGROUND: Left ventricular (LV) dysfunction plays a primary role in the pathogenesis of congestive heart failure and correlates with prognosis, but a strong quantitative relation between exercise performance and indexes of LV function has not been demonstrated. We examined the relation between LV ejection fraction at rest, oxygen consumption at peak exercise (VO2), patient and physician assessments of clinical severity, and other clinical attributes in 804 patients with moderate heart failure. METHODS AND RESULTS: Ejection fraction correlated weakly with VO2, and mean ejection fraction was related to severity of symptoms. There was a statistical association between the patient's self-assessed quality of life questionnaire score and the physician-assigned New York Heart Association (NYHA) functional class; NYHA class was statistically associated with exercise performance. To identify other factors that might influence exercise capacity, comparisons of clinical attributes were made between patients grouped by VO2 within each stratum of LV function. Exercise performance was inversely related to plasma norepinephrine levels within the ejection fraction < 25% stratum. The percentage of patients reaching their anaerobic threshold was not different between groups, yet the peak heart rate increased with VO2 within all strata. Elevated venous pressure and cardiomegaly were inversely related to exercise performance. CONCLUSIONS: Clinical scales based on physician and patient assessment of symptoms were statistically associated with exercise capacity but do not accurately predict individual exercise performance. The strong association of heart rate response to exercise performance suggests that the variability of the chronotropic response to exercise contributes to differences in exercise capacity among patients with a similar degree of LV dysfunction.

Drug Therapy, Combination↗
PubMed1992

Increased costs and rates of use in the California workers' compensation system as a result of self-referral by physicians.

BACKGROUND: There is widespread concern that ownership by physicians of testing or treatment facilities to which they refer patients leads to overuse of such facilities. We determined the patterns of use of three services--physical therapy, psychiatric evaluation, and magnetic resonance imaging (MRI)--among physicians treating patients whose care was covered under workers' compensation. We then compared the rates of use among physicians who referred patients to facilities of which they were owners (self-referral group) with the rates among physicians who referred patients to independent facilities (independent-referral group). METHODS: We used a large data base to analyze claims under workers' compensation in California from October 1, 1990, through June 30, 1991, to determine the frequency and cost of these three selected services and determined whether the referring physicians were practicing self-referral or independent referral. We evaluated the cost per case for all three services, measured the frequency with which physical therapy was initiated, and evaluated the medical appropriateness of MRI. RESULTS: We found that physical therapy was initiated 2.3 times more often by the physicians in the self-referral group (68 percent) than by those in the independent-referral group (30 percent; P < 0.01). The mean cost per case for physical therapy was significantly lower in the self-referral group ($404 +/- 102) than in the independent-referral group ($440 +/- 167; P < 0.01). The mean cost of psychiatric evaluation services was significantly higher in the self-referral group than in the independent-referral group (psychometric testing, $1,165 +/- 728 vs. $870 +/- 482; P < 0.01, psychiatric evaluation reports, $2,056 +/- 1,063 vs. $1,680 +/- 578; P < 0.01). The total cost per case of psychiatric evaluation services was 26.3 percent higher in the self-referral group ($3,222 +/- 1,451) than in the independent-referral group ($2,550 +/- 742; P < 0.01). Of all the MRI scans requested by the self-referring physicians, 38 percent were found to be medically inappropriate, as compared with 28 percent of those requested by physicians in the independent-referral group (P < 0.05). There was no significant difference in the cost per case between the two groups. CONCLUSIONS: This study demonstrates that self-referral increases the cost of medical care covered by workers' compensation for each of the three types of service studied.

Ambulatory Care Facilities↗
PubMed1992

Pneumonia associated with Salmonella choleraesuis infection in swine: 99 cases (1987-1990).

Salmonella choleraesuis was isolated in pure or mixed bacterial cultures from 153 swine necropsied between Jan 1, 1987 and Dec 31, 1990. Pneumonia was seen in 99 of 109 swine from which this bacterium was isolated in the absence of other pathogenic bacteria. Pneumonia was seen more frequently than hepatitis, splenomegaly, or colitis. Pleuropneumonia that was grossly indistinguishable from the pleuropneumonia associated with Actinobacillus pleuropneumoniae was seen in 29 of 99 swine from which S choleraesuis was the only bacterium isolated.

Animals↗
PubMed1992

Generation of N-methyl-D-aspartate agonist and competitive antagonist pharmacophore models. Design and synthesis of phosphonoalkyl-substituted tetrahydroisoquinolines as novel antagonists.

The preparation and binding affinity of a series of tetrahydroisoquinoline carboxylic acids at the N-methyl-D-aspartate (NMDA) subtype of the glutamate receptor is described, together with a molecular modeling analysis of NMDA agonists and antagonists. Using published NMDA ligands, the active analogue mapping approach was employed in the generation of an agonist pharmacophore model. Although known competitive antagonists such as CPP (1) could be superimposed onto the agonist model, to overcome the assumption that they bind to the same receptor site, an independent modeling approach was used to derive a separate pharmacophore model. Development of a competitive antagonist model involved a stepwise approach that included the definition of a preferred geometry for PO3H2-receptor interactions, multiple conformational searches, and the determination of volume and electronic tolerances. This model, which is described in detail, is consistent with observed affinities of potent NMDA antagonists and has provided an explanation for the observed periodicity in affinities for the known antagonists AP5, AP6, and AP7. The features of the agonist and antagonist models are compared, and hypotheses advanced about the nature of the receptor interactions for these two classes of compounds. The pharmacophore models reported herein are consistent with a single recognition site at the NMDA receptor that can accommodate both agonist and antagonist ligands. To assist in first defining and later exploring the predictive power of the competitive antagonist model, a series of conformationally constrained NMDA antagonist (phosphonoalkyl)tetrahydroisoquinoline-1- and 3-carboxylates was prepared. From this work, 1,2,3,4-tetrahydro-5-(2-phosphonoethyl)-3- isoquinolinecarboxylic acid (89) was identified as the most active lead structure, with an IC50 of 270 nM in [3H]CPP binding. The synthesis and structure-activity relationships of these novel antagonists are described.

Binding, Competitive↗