[Affine sorbent with typtophil-threonil-tirosine for binding immunoglobulin G: sorption characteristics and aspects of practical application].

New chromatographic material based on tryptophil-threonil-tirosine was prepared. This sorbent effectively binds human, sheep, goat and cow immunoglobulins G. New sorbent shows high selectivity for removing immunoglobulins from blood plasma. Effective sorption capacity is 15-25 mg of immunoglobulin G per ml of matrix. Optimal method of covalent attachment ligand to polysaccharide matrix allows achieving high stability of the sorbents in terms of use and storage. This sorbent can be used in medicine and biotechnology.

[The synthesis of immunomodulating peptide alloferon, the active component of the antiviral drug allokine-alpha].

Two variants of the synthesis of tridecapeptide alloferon, the active principle of antiviral preparation allokine-alpha, were developed on the basis of fragment condensation in solution or on the Merrifield resin. The solid phase variant of the synthesis was shown to be more technological; it allows the preparation of the product at a higher total yield (40% vs. 17% for conventional synthesis in solution from the starting derivatives of the C-terminal dipeptide). The by-products formed during the synthesis of alloferon were identified.

Atrophy rate in medial temporal lobe during progression of Alzheimer disease.

OBJECTIVE: To establish the progression of brain atrophy rates in patients with a known date of onset of Alzheimer disease (AD). METHODS: Each of 18 subjects had two high-resolution T1-weighted three-dimensional MRI examinations. The two MRIs were coregistered and the annual rate of brain tissue atrophy was derived both for the entire brain and regionally for the left and right medial temporal lobe (MTL). Time since onset (TSO) of AD, defined as the interval between the date of onset and the midpoint of MRI dates, ranged from -2.9 to 4.2 years. RESULTS: In patients with AD, TSO was a correlate of the atrophy rate for both the left MTL (R2 = 0.58, p = 0.001) and right MTL (R2 = 0.30, p = 0.03). When serial measurements were applied to a control group of 21 cognitively normal elderly subjects, MTL atrophy rate classified the group membership (AD vs normal cognition) with an accuracy of 92.3%. CONCLUSION: Increased annual atrophy rate in the medial temporal lobe is a potential diagnostic marker of the progression of Alzheimer disease.

Acute effects of exercise on cognition in patients with chronic obstructive pulmonary disease.

Prior data indicate positive effects of long-term exercise interventions for cognitive functioning among patients with chronic obstructive pulmonary disease (COPD), but no prior studies have examined acute effects of individual bouts of exercise among patients with COPD. This study evaluated acute effects of exercise on cognitive performance in a community-based sample of patients with COPD and a healthy control group, matched by age, sex, and education. Twenty-nine older adults with COPD (mean age = 67.8 yr [+/- 7.4]; range: 56-85; 17 women) and 29 matched healthy control subjects (mean age = 68.7 yr [+/- 6.0] ) were recruited from the community. All participants completed a 20-min exercise session in which they exercised to a peak level and a video control condition in which they were provided information about exercise and cholesterol. Conditions were separated by a 1-wk interval, and order of participation in conditions was randomly assigned. Assessments of cognitive performance (Trail Making Test, Digit Symbol, Verbal Fluency, Digit Span, Finger Tapping) were administered before and after each condition (exercise and video). Among patients with COPD, acute exercise was associated with improved performance on the Verbal Fluency test, a measure of verbal processing, suggesting that acute exercise may benefit aspects of cognitive performance among patients with COPD.

Leveraging healthcare for the greater good: lessons learned from the National Centers of Excellence in Women's Health.

The creation of the National Centers of Excellence in Women's Health (CoE) program in 1996 by the Office on Women's Health, Department of Health and Human Services, included the stipulation that each institution awarded a CoE contribute at least a 25% match for the federal funds. Even the combination of these two sources of monies was insufficient for each CoE to accomplish its goals, however, so leveraging funds became necessary for each CoE to function effectively. The forms of leveraging varied from CoE to CoE, in part as a result of the institutional environment and the unique possibilities each permitted and in part as a result of the creativity of the leaders of the CoEs. This paper describes the concepts and some applications of leveraging in the setting of the CoEs, which might be applicable to other settings as well.

Circadian rhythm and sudden death in heart failure: results from Prospective Randomized Amlodipine Survival Trial.

OBJECTIVE: The purpose of this study was to address the timing of sudden death in advanced heart failure patients. BACKGROUND: Sudden death is a catastrophic event in cardiovascular disease. It has a circadian pattern prominent in the early AM, which has been thought to be due to a surge of sympathetic stimulation. We postulated that the distribution of events in advanced heart failure, with chronic sympathetic activation, would be more uniform implicating other potential mechanisms. METHODS: We analyzed data from Prospective Randomized Amlodipine Survival Trial (PRAISE). Sudden deaths were analyzed by time of death in 4-h and 1-h blocks for uniformity of distribution in the entire cohort, and in the prespecified ischemic and nonischemic stratum. Further analyses were undertaken in the treatment groups of amlodipine and placebo, and among those receiving background therapy of aspirin and warfarin. RESULTS: Sudden deaths in the overall cohort showed a nonuniform distribution with a PM peak but not an AM peak. The ischemic stratum also showed a PM peak, but sudden deaths within the nonischemic stratum were uniformly distributed. Neither amlodipine treatment nor aspirin or warfarin use altered the distribution. CONCLUSIONS: Sudden death in advanced heart failure did not show an AM peak, suggesting that circadian sympathetic activation did not strongly influence these events. The PM peak noted is likely complex in origin and was not affected by antiischemic or antithrombotic medications.

Depression as an antecedent to heart disease among women and men in the NHANES I study. National Health and Nutrition Examination Survey.

BACKGROUND: Depression predicts morbidity and mortality among individuals who have coronary heart disease (CHD), and there is increasing evidence that depression may also act as an antecedent to CHD. The studies that have reported a relationship between depression and CHD incidence or mortality either were restricted to men only or analyzed women and men together. The present investigation was conducted to evaluate the differential effect depression may have on CHD incidence and mortality in women and men. RESEARCH METHODS: We analyzed data from 5007 women and 2886 men enrolled in the first National Health and Nutrition Examination Survey (NHANES I) who were free of CHD at the 1982-1984 interview and who had completed the Center for Epidemiologic Studies Depression Scale (CES-D). Participants were evaluated from the 1982 interview date either until the end of the study (1992 interview date) or until the occurrence of a CHD event. Using CHD incidence and CHD mortality (International Classification of Disease, Ninth Revision, codes 410-414) as the outcome variables, Cox proportional hazards regression models were developed to evaluate the relative risk (RR) of CHD incidence and mortality in the depressed women and men separately, controlling for standard CHD risk factors. RESULTS: The women experienced 187 nonfatal and 137 fatal events, compared with 187 nonfatal and 129 fatal events among the men. The adjusted RR of CHD incidence among depressed women was 1.73 (95% confidence internal [CI], 1.11-2.68) compared with nondepressed women. Depression had no effect on CHD mortality in the women (RR, 0.74; 95% CI, 0.40-1.48). The adjusted RR of CHD incidence among depressed men was 1.71 (95% CI, 1.14-2.56) compared with nondepressed men. Depressed men also had an increased risk of CHD mortality compared with their nondepressed counterparts, with an adjusted RR of 2.34 (95% CI, 1.54-3.56). CONCLUSIONS: In this sample, while controlling for possible confounding factors, depression was associated with an increased risk of CHD incidence in both men and women, as well as CHD mortality in men. Depression had no effect on CHD mortality in women.

Continuous handrail support, oxygen uptake, and heart rate in women during submaximal step treadmill exercise.

Past research suggests that continuous handrail support during exercise attenuates physiologic responses to exercise and reduces aerobic benefits; however, this phenomenon has not been systematically studied in women exercising on the step treadmill. The effects of three levels of handrail support (continuous light, continuous very light, or no handrail support) on oxygen uptake and heart rate during step treadmill exercise were examined in 15 healthy women. Measures were obtained during 6 bouts of exercise, 3 bouts at 25 steps/min followed by 3 bouts at 33 steps/min. At both step rates, mean oxygen uptake was significantly reduced during continuous light and continuous very light handrail support as compared with no handrail support, and mean heart rate was significantly reduced during continuous light versus no handrail support. At 25 steps/min only, mean heart rate was significantly reduced during continuous very light versus no handrail support. Findings indicate that women who use even continuous light or continuous very light handrail support attenuate physiologic responses during step treadmill exercise, thereby reducing aerobic requirements and gaining suboptimal benefits from exercise.

Short term citrus flavonoid supplementation of type II diabetic women: no effect on lipoprotein oxidation tendencies.

Flavonoids, which are dietary components and have possible drug uses, inhibit lipoprotein oxidation in vitro. The present study considered whether flavonoid supplementation in humans could influence lipoprotein vulnerability to oxidation. Citrus flavonoid supplementation (about 1g/day, 3 weeks), or placebo, was given to 40 Type II diabetic women, a population prone to oxidative stress. Absorbance spectra of plasma from 4 subjects revealed that some flavonoid absorption occurred. When tested in vitro, a supplement extract, with spectrum peak height similar to that of plasma samples, completely inhibited copper-induced oxidation of very low plus low density lipoproteins. In contrast, neither flavonoid supplementation nor placebo influenced lipoprotein susceptibility to copper-stimulated oxidation in vitro (lag time or propagation rate). Thus, this study demonstrated that increased flavonoid consumption by humans does not necessarily alter lipoprotein susceptibility to oxidation assessed in vitro.

Effect of amlodipine on mode of death among patients with advanced heart failure in the PRAISE trial. Prospective Randomized Amlodipine Survival Evaluation.

Investigations of calcium antagonists in patients with advanced heart failure have raised concern over an increased risk of worsening heart failure and heart failure deaths. We assessed the effect of amlodipine on cause-specific mortality in such patients enrolled in a randomized, double-blind, placebo-controlled trial. In total, 1,153 patients in New York Heart Association class IIIb or IV heart failure were randomized to receive amlodipine or placebo, along with angiotensin-converting enzyme inhibitors, diuretics, and digitalis. Over a median 14.5 months of follow-up, 413 patients died. Cardiovascular deaths accounted for 89% of fatalities, 50% of which were sudden deaths and 45% of which were due to pump failure, with fewer attributed to myocardial infarction (3.3%) or other cardiovascular causes (1.6%). Amlodipine treatment resulted in a greater relative reduction in sudden deaths (21%) than in pump failure deaths (6.6%) overall. When patients were classified by etiology of heart failure (ischemic or nonischemic), cause-specific mortality did not differ significantly between treatment groups in the ischemic stratum. In the nonischemic stratum, however, sudden deaths and pump failure deaths were reduced by 38% and 45%, respectively, with amlodipine. Thus, when added to digitalis, diuretics, and angiotensin-converting enzyme inhibitors in patients with advanced heart failure, amlodipine appears to have no effect on cause-specific mortality in ischemic cardiomyopathy, but both pump failure and sudden deaths appear to be decreased in nonischemic heart failure patients treated with amlodipine.

Stepping as an exercise modality for improving fitness and function.

This article describes three stepping modes, summarizes research on stepping in healthy adults and patients with peripheral vascular disease, and discusses clinical implications and directions for future research. Stepping exercise has been shown to increase cardiorespiratory fitness in healthy adults and increase physical function in patients with peripheral vascular disease. Although further research is warranted, stepping exercise has potential value as a nursing intervention to correct alterations in physical mobility in selected populations. Stepping is proposed as an alternative exercise strategy; one which adds variety to exercise routines and may enhance long-term exercise adherence.

Evaluation of a commercial accelerometer (Tritrac-R3 D) to measure energy expenditure during ambulation.

This study evaluated the ability of a commercially available accelerometer (Tritrac-R3 D) to measure energy expenditure in 16 subjects at rest (pre- and post-exercise) and during three different intensities of steady-state exercise (40-70% of peak oxygen consumption [VO2peak]) while ambulating on a treadmill (no grade). Oxygen consumption and the respiratory exchange ratio from indirect calorimetry and the vector magnitude of triaxial accelerations were used to estimate energy expenditure using the manufacturers' equations. There was a significant relationship between indirect calorimetry-derived energy expenditure and the energy expenditure derived from the accelerometer (r=0.96). Using analysis of variance, there was no difference in the energy expenditure derived by the two methods at rest before exercise and during the three different intensities of ambulatory exercise. There was a significant difference between energy expenditure derived via indirect calorimetry and with the accelerometer during rest after exercise, probably due to the failure of the accelerometer to accurately estimate the energy expenditure associated with the progressive decline in post-exercise oxygen consumption. Thus, this commercially available accelerometer appears to provide statistically acceptable estimates of energy expenditure at rest and during zero-grade treadmill ambulation up to about 70% VO2peak. This may indicate its acceptable utility for large-scale population studies of physical activity involving this mode of movement. The failure of the accelerometer to accurately estimate energy expenditure during recovery from exercise may contribute to an underestimation of energy expenditure in some physically active individuals.

Stability over time of circadian rhythm of variability of heart rate in patients with stable coronary artery disease.

Reproducibility of circadian rhythm of variability in heart rate was studied in 40 patients with stable coronary artery disease who underwent 48-hour ambulatory electrocardiographic recordings at baseline (time 1) and after 4 months (time 2). The standard deviation of the R-R interval and the low-frequency (0.04 to 0.15 Hz) and high-frequency (0.15 to 0.45 Hz) components of variability in heart rate were assessed every 5 minutes. In 35 patients a significant circadian rhythm was observed at both time 1 and time 2 in the standard deviation of the R-R interval, with the acrophase occurring at around 5:00 AM, in the high-frequency amplitude with the acrophase around 3:00 AM, and in the low-frequency/high-frequency ratio with the acrophase around noon. In these patients, parameters of circadian rhythm (mesor, amplitude, and acrophase) showed good within-individual reproducibility with an intraclass correlation coefficient of 0.63 to 0.95 (p < 0.001 for all). In the patients who showed inconsistency about the significance of circadian rhythm between time 1 or time 2, the amplitude of circadian rhythm, even if significant, was found in the lowest five values in the distribution. We conclude that the circadian rhythms of cardiac autonomic activity are stable over time within individual patients with stable coronary artery disease.

Stress management and exercise training in cardiac patients with myocardial ischemia. Effects on prognosis and evaluation of mechanisms.

BACKGROUND: Previous studies have demonstrated that myocardial ischemia can be elicited by mental stress in the laboratory and during daily life and that ischemia induced by mental stress is associated with an increased risk for future cardiac events in patients with coronary artery disease. OBJECTIVES: To examine the extent to which ischemia induced by mental stress can be modified by exercise stress management, and to evaluate the impact of these interventions on clinical outcomes. METHODS: One hundred seven patients with coronary artery disease and ischemia documented during mental stress testing or ambulatory electrocardiographic monitoring were randomly assigned to a 4-month program of exercise or stress management training. Patients living at a distance from the facility formed a nonrandom, usual care comparison group. Myocardial ischemia was reassessed following treatment, and patients were contacted annually for as long as 5 years to document cardiac events, including death, nonfatal myocardial infarction, and cardiac revascularization procedures. RESULTS: Twenty-two patients (21%) experienced at least 1 cardiac event during a mean (+/- SD) follow-up period of 38 +/- 17 months. Stress management was associated with a relative risk of 0.26 compared with controls. The relative risk for the exercise group also was lower than that of controls, but the effect did not reach statistical significance. Stress management also was associated with reduced ischemia induced by mental stress and ambulatory ischemia. CONCLUSION: These data suggest that behavioral interventions offer additional benefit over and above usual medical care in cardiac patients with evidence of myocardial ischemia.

Short-term zinc supplementation in women with non-insulin-dependent diabetes mellitus: effects on plasma 5'-nucleotidase activities, insulin-like growth factor I concentrations, and lipoprotein oxidation rates in vitro.

Non-insulin-dependent diabetes mellitus (NIDDM) may cause vulnerability to moderate zinc deficiency. In this study, short-term zinc supplementation (30 mg/d as amino acid chelate for 3 wk) elevated plasma zinc and activities of 5'-nucleotidase, a zinc-dependant enzyme, in 20 postmenopausal women with NIDDM. Placebo, given to 20 other women with NIDDM, had no effects on these indexes nor on any others taken in this study. Although zinc supplementation doubled the mean value for 5'-nucleotidase activity, values were still significantly lower than those of age-matched control subjects. Plasma insulin-like growth factor I concentrations increased with zinc treatment if starting concentrations were < 165 microg/L but were unchanged if they were > 165 microg/L. Lipoprotein oxidation in vitro, which has abnormal lag times and propagation rates for subjects with NIDDM and for moderately zinc-deficient rats, were unchanged by zinc supplementation. Possibly, this lack of effect occurred because the zinc treatment did not normalize zinc status. In conclusion, this study supports the contention that moderate zinc deficiency occurs frequently in subjects with NIDDM.

Effects of mental stress on myocardial ischemia during daily life.

OBJECTIVE: To determine the relative risk of myocardial ischemia triggered by specific emotions during daily life. DESIGN AND SETTING: Relative risk was calculated by the recently developed case-crossover method, in which the frequency of a presumed trigger during nonischemic, or control, hours is compared with the trigger's frequency during ischemic, or case, hours. Outpatients at Duke University Medical Center, Durham, NC, underwent 48 hours of ambulatory electrocardiographic (ECG) monitoring with concurrent self-report measures of activities and emotions. Occurrences of negative emotions in the hour before the onset of myocardial ischemia were compared with their usual frequency based on all hours in which ischemia did not occur. SUBJECTS: From a sample of 132 patients with coronary artery disease and recent evidence of exercise-induced ischemia who underwent 48 hours of ambulatory ECG monitoring, 58 patients exhibited ambulatory ischemia and were included in the analysis. OUTCOME MEASURES: Myocardial ischemia during 48-hour ECG monitoring was defined as horizontal or downsloping ST-segment depression of 1 mm (0.1 mV) or more for 1 minute or longer compared with resting baseline. The ECG data were cross-tabulated with subjects' concurrent diary ratings of 3 negative emotions-tension, sadness, and frustration-and 2 positive emotions-happiness and feeling in contro-on a 5-point scale of intensity. RESULTS: The unadjusted relative risk of occurrence of myocardial ischemia in the hour following high levels of negative emotions was 3.0 (95% confidence interval [CI], 1.5-5.9; P<.01) for tension, 2.9 (95% CI, 1.0-8.0; P<.05) for sadness, and 2.6 (95% CI, 1.3-5.1; P<.01) for frustration. The corresponding risk ratios adjusted for physical activity and time of day were 2.2 (95% CI, 1.1 -4.5; P<.05) for tension, 2.2 (95% CI, 0.7-6.4; P=.16) for sadness, and 2.2 (95% CI, 1.1-4.3; P<.05) for frustration. CONCLUSIONS: Mental stress during daily life, including reported feelings of tension, frustration, and sadness, can more than double the risk of myocardial ischemia in the subsequent hour. The clinical significance of mental stress-induced ischemia during daily life needs to be further evaluated.

Step treadmill exercise training and blood pressure reduction in women with mild hypertension.

Stepping as an exercise modality has gained increasing popularity. The step treadmill is an exercise machine which simulates actual stair-climbing. The purpose of this study was to determine the effectiveness of a 16-week supervised aerobic step treadmill exercise training protocol in reducing resting blood pressure in women with unmedicated mild hypertension. During the training protocol, subjects exercised during a self-selected appointment three times a week on the step treadmill, increasing from 20 minutes up to 60 minutes per session, at a target heart rate corresponding to 70-80% heart rate reserve for 16 weeks. Utilizing paired t-test analysis, mean resting systolic blood pressure decreased from 142.2 +/- 9.1 to 132.7 +/- 8.2 mm Hg (p < .01) and mean resting diastolic blood pressure decreased from 93 +/- 4.9 to 87.4 +/- 5.4 mm Hg (p < .01) during the 16-week protocol. Mean maximal oxygen uptake was significantly increased, whereas mean body weight did not change significantly over the 16-week period. Large scale trials are needed to further delineate the effectiveness of stepping as a health care intervention in adults with unmedicated mild hypertension, especially in women.

Effect of amlodipine on morbidity and mortality in severe chronic heart failure. Prospective Randomized Amlodipine Survival Evaluation Study Group.

BACKGROUND: Previous studies have shown that calcium-channel blockers increase morbidity and mortality in patients with chronic heart failure. We studied the effect of a new calcium-channel blocker, amlodipine, in patients with severe chronic heart failure. METHODS: We randomly assigned 1153 patients with severe chronic heart failure and ejection fractions of less than 30 percent to double-blind treatment with either placebo (582 patients) or amlodipine (571 patients) for 6 to 33 months, while their usual therapy was continued. The randomization was stratified on the basis of whether patients had ischemic or nonischemic causes of heart failure. The primary end point of the study was death from any cause and hospitalization for major cardiovascular events. RESULTS: Primary end points were reached in 42 percent of the placebo group and 39 percent of the amlodipine group, representing a 9 percent reduction in the combined risk of fatal and nonfatal events with amlodipine (95 percent confidence interval, 24 percent reduction to 10 percent increase; P=0.31). A total of 38 percent of the patients in the placebo group died, as compared with 33 percent of those in the amlodipine group, representing a 16 percent reduction in the risk of death with amlodipine (95 percent confidence interval, 31 percent reduction to 2 percent increase; P=0.07). Among patients with ischemic heart disease, there was no difference between the amlodipine and placebo groups in the occurrence of either end point. In contrast, among patients with nonischemic cardiomyopathy, amlodipine reduced the combined risk of fatal and nonfatal events by 31 percent (P=0.04) and decreased the risk of death by 46 percent (P<0.001). CONCLUSIONS: Amlodipine did not increase cardiovascular morbidity or mortality in patients with severe heart failure. The possibility that amlodipine prolongs survival in patients with nonischemic dilated cardiomyopathy requires further study.

Mental stress--induced myocardial ischemia and cardiac events.

OBJECTIVE: To assess the clinical significance of mental stress-induced myocardial ischemia in patients with coronary artery disease (CAD). DESIGN AND SETTING: Cohort study in outpatients in a tertiary care teaching hospital assessed at baseline and followed up for up to 5 years. SUBJECTS: A total of 126 volunteer patients (112 men, 14 women; mean age, 59 years) with documented CAD and exercise-induced myocardial ischemia. OUTCOME MEASURES: Patients underwent baseline mental stress and exercise testing using radionuclide ventriculography and 48-hour Holter monitoring. Patients were subsequently contacted by mailed questionnaires or telephone to document cardiac events, including death, nonfatal myocardial infarction, and cardiac revascularization procedures. Logistic regression and Cox proportional hazards models were used to examine the prognostic value of the ischemic measures after adjusting for such potential confounding factors as age, baseline left ventricular ejection fraction (LVEF), and history of myocardial infarction. RESULTS: Twenty-eight patients (22%) experienced at least 1 cardiac event. Baseline mental stress-induced ischemia was associated with significantly higher rates of subsequent cardiac events (odds ratio, 2.8; 95% confidence interval [CI], 1.0-7.7; P < .05). The LVEF change during mental stress was significantly related to event-free survival (risk ratio [RR], 2.4; 95% CI, 1.12-5.14; P = .02), controlling for age, history of prior myocardial infarction, and baseline LVEF. This relationship remained significant after controlling for electrocardiogram (ECG)-defined ischemia during exercise (RR, 2.2; 95% CI, 1.01-4.81; P < .05). The RR for ECG-defined ischemia during exercise testing was 1.9 (95% CI, 0.95-3.96; P = .07) and the RR for ambulatory ECG ischemia was 0.75 (95% CI, 0.35-1.64; P = .47). CONCLUSIONS: The presence of mental stress-induced ischemia is associated with significantly higher rates of subsequent fatal and nonfatal cardiac events, independent of age, baseline LVEF, and previous myocardial infarction, and predicted events over and above exercise-induced ischemia. These data suggest that the relationship between psychological stress and adverse cardiac events may be mediated by the occurrence of myocardial ischemia.