Can the genetic factors influence the treatment of systemic hypertension? The case of the renin-angiotensin-aldosterone system. The hereditary nature of familial hypertension has been clearly established by a number of clinical studies. About 30% of the blood pressure variance can be attributed to genetic factors. As a consequence, the relative risk for developing coronary artery disease or cardiovascular death is increased in patients with a family history of hypertension and cardiovascular disease. Patients with such familial history should be considered at the same risk as those who have independent epidemiologic risk factors. The development of molecular genetics allows establishment of a link between high blood pressure, intermediate phenotypes, and the genes involved in blood pressure regulation. Gene markers should be available in the near future that will help to identify patients predisposed to hypertension. The genes of the renin-angiotensin-aldosterone system are good examples of candidate genes whose products are known to participate in blood pressure regulation. The possible involvement of these genes in essential hypertension is critically analyzed.


Prevention of myocardial infarction.

Prevention of myocardial infarction. Despite substantial progress in cardiovascular disease prevention, stroke and myocardial infarction remain the leading causes of death throughout the industrialized world. Treatment of high blood pressure, while contributing importantly to this progress, remains inefficient and less than optimally effective, particularly in regard to coronary artery disease events. Therapeutic intervention in the renin-angiotensin system offers promise of progress on both these fronts. Renin-sodium profiles have been shown to permit prognostic stratification of otherwise indistinguishable hypertensive patients. Indeed, low renin subjects, without other cardiovascular risk factors, have a particularly favorable prognosis. Now, the pharmacologic ability to mute the pathologic effects of angiotensin II also offers the genuine possibility that the cardioprotective value of antihypertensive therapy may be significantly improved.


Trandolapril in hypertension: overview of a new angiotensin-converting enzyme inhibitor. Trandolapril is a new angiotensin-converting enzyme (ACE) inhibitor that has been extensively investigated in vitro, in animals, in normal volunteers, and in hypertensive patients. It has been shown to exert all the effects typical for the class of ACE inhibitors, and has a marked impact on the reversal of structural hypertrophy of the myocardium and the arterial wall. Trandolapril is a prodrug that must be hydrolyzed to its active metabolite, trandolaprilat. This latter compound exhibits a particularly high affinity for converting enzyme, which results in a slow dissociation and one of the longest durations of action of any converting enzyme inhibitor known so far. Trandolapril reduces blood pressure consistently throughout the 24-hour period following intake. Accordingly, trandolapril, more than any other drug of its class, can be considered a true, once-a-day antihypertensive drug.


Effects of trandolapril on vascular morphology and function during the established phase of systemic hypertension in the spontaneously hypertensive rat. The aim of this study was to determine the morphologic and functional vascular changes occurring following 4 weeks of treatment with the angiotensin-converting enzyme inhibitor trandolapril in the spontaneously hypertensive rat (SHR) in the established phase of hypertension. At the dosage used, 0.4 mg/kg orally, trandolapril decreased blood pressure of the SHR by 15-18% compared with that of the control animals. Immediately before the end of treatment, the following changes from control values were observed: (1) 9, 11, and 12% reductions for myocardial hypertrophy and the media thickness of the thoracic aorta and femoral arteries, respectively; and (2) an increase in the compliance of the resistance arteries, demonstrated by a shift to the right of the in vitro tension-diameter curves and a significant 22% increase in their normalized internal diameter, while their maximum contractile ability was significantly decreased. Following discontinuation of treatment, blood pressure levels remained significantly lower in the treated versus the control groups for up to 4 weeks after the last administration. At that time measurement of the studied parameters showed: (1) a rapid reversion to control values of the compliance of the resistance vessels; and (2) a slower progression, but in the same direction, in the parameters of cardiac and vascular hypertrophy. Thus, trandolapril, administered for a short period in the adult SHR, was able to reverse the cardiac and vascular morphologic changes present in this model of hypertension. Like the effect on blood pressure, these effects were slowly reversible at the end of treatment, whereas the functional consequences at the resistance artery level seemed to display a more rapid reversibility.


Clinical value of blood pressure measurements: focus on ambulatory blood pressures. Because clinic blood pressure values are compromised by 2 major limitations--the alerting reaction to clinic measurements and the spontaneous blood pressure variability--they have only a limited correlation with average 24-hour blood pressure values. Whether the latter should be employed routinely in substitution for, or in addition to, traditional blood pressure measurements has not yet been determined, however. To date, average 24-hour blood pressure values have been shown to correlate more closely than clinic blood pressure values with the organ damage of hypertension. A correlation with organ damage has been shown also for a number of blood pressure values within the 24 hours. Nevertheless, the clinical importance of 24-hour blood pressure and blood pressure variability has never been confirmed by prospective controlled studies. This information needs to be obtained before this approach is routinely employed in the clinical practice.


Beneficial effects of trandolapril on experimentally induced congestive heart failure in rats. Angiotensin-converting enzyme (ACE) inhibitors have been shown to prolong life expectancy in patients with congestive heart failure. In order to determine the relative contributions of the different factors involved in this beneficial effect, we investigated in an experimental model of postinfarction cardiac insufficiency in the rat over a 9-12-month period (1) the kinetics of the development of the hemodynamic, biologic, and morphologic alterations that accompany heart failure, and (2) the kinetics of the effects of a new, long-acting ACE inhibitor, trandolapril. Following induction of infarction, systolic blood pressure, left ventricular dP/dt, and end-diastolic pressure were immediately decreased, decreased, and increased, respectively, and these modifications persisted throughout the study. Cardiac index, on the other hand, was only initially and transiently decreased. Cardiac remodeling (left ventricular dilation, myocardial hypertrophy, and fibrosis) occurred as early as 7 days after infarction and worsened throughout the study. Plasma atrial natriuretic factor (ANF) and urinary cyclic guanosine monophosphate (cGMP) were also increased. In this model, a 1-year oral treatment with trandolapril resulted in early hemodynamic and biologic beneficial effects (reductions in pre- and afterload, increase in cardiac index, and decrease in plasma ANF), and in a delayed reversal of the infarction-induced cardiac morphologic alterations. Hence, the trandolapril-induced increase in survival rate is due initially to the drug's hemodynamic effects and over the long-term to both its hemodynamic and cardiac morphologic (limitation of remodeling) effects.


Reversal of cardiac and large artery structural abnormalities induced by long-term antihypertensive treatment with trandolapril. In 15 patients with untreated mild to moderate essential hypertension and left ventricular hypertrophy, we assessed blood pressure, echocardiographic left ventricular mass index, brachial artery compliance (pulsed doppler flowmetry), and calculated forearm vascular resistance (strain gauge plethysmography) before, during (6 and 12 months) and after (1 month washout period) 1 year of satisfactory (blood pressure < or = 140/90 mm Hg) antihypertensive therapy with the angiotensin-converting enzyme inhibitor trandolapril (2.0 mg orally once daily). During the antihypertensive effective treatment, we observed a significant reduction of systolic and diastolic blood pressures, left ventricular mass index, and forearm vascular resistance at both 6 and 12 months. In addition, brachial artery compliance was significantly increased. After washout, systolic (156 +/- 3 mm Hg) and diastolic (102 +/- 1 mm Hg) blood pressures returned to levels comparable to baseline. However, left ventricular mass index (132 +/- 4; p < 0.01) and brachial artery compliance (1.53 +/- 0.01; p < 0.01) were still different from baseline. These results demonstrate that chronic antihypertensive treatment with trandolapril is associated with a stable regression of cardiac and vascular abnormalities, which is partially unrelated to the blood pressure lowering effect.


Evaluation of the antihypertensive effect of once-a-day trandolapril by 24-hour ambulatory blood pressure monitoring. The Italian Trandolapril Study Group. The aim of this study was to evaluate the effects of trandolapril on 24-hour blood pressure in patients with mild-to-moderate essential hypertension. After a washout period of 4 weeks, 42 patients were randomized to receive 2 mg of trandolapril once daily and 20 to receive placebo in a double-blind fashion for 6 weeks. This was followed by a second washout period of 4 weeks. At the end of each period, clinic blood pressure was assessed at 24 hours after the last dose and 24-hour ambulatory blood pressure was measured noninvasively, taking blood pressure readings every 15 minutes during the day and every 20 minutes during the night. Two patients were dropped out before any blood pressure evaluation under treatment. Analysis of ambulatory blood pressure was performed in 48 patients who met the criteria for the minimal number of ambulatory blood pressure data (2 values per hour during the day and 1 value per hour in the night). In the trandolapril-treated group (n = 41) clinic systolic/diastolic blood pressures were 159.8 +/- 2.0/102.4 +/- 0.8, 146.8 +/- 2.3/94.8 +/- 1.1, and 155.7 +/- 2.0/99.2 +/- 0.7 mm Hg in the pretreatment, treatment, and post-treatment periods, respectively. The corresponding values for 24-hour mean blood pressure (n = 31) were 139.5 +/- 1.9/91.2 +/- 1.5, 131.0 +/- 2.0/84.3 +/- 1.2, and 139.7 +/- 1.8/90.9 +/- 1.1 mmHg. The differences between the lower treatment, versus the higher pre- and post-treatment, values were all statistically significant (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)


After the diagnosis of systemic hypertension, is risk factor management important? In the hypertensive patient, the presence of other cardiovascular risk factors, particularly smoking, hypercholesterolemia, obesity, and diabetes, greatly influences the prognosis. In many patients, these other risk factors are linked, perhaps by adverse effects of pressure on endothelial function. The newer antihypertensive agents may have better effects on prognosis by ameliorating these other risk factors, as well as lowering pressure. We await trials to see if this promise is fulfilled.


Influence of vessel selection on the observed restenosis rate after endoluminal stenting or directional atherectomy. In comparing the restenosis rates among different interventions, 1 potential confounder might be the differences in the vessels treated, as dictated by the technical limitations of particular devices. The purpose of this study was to use current "acute gain-late loss" analysis to examine what influence vessel selection has on the restenosis rates seen after coronary stenting or directional atherectomy. The minimal luminal diameter of native coronary lesions was measured before and immediately after intervention in 102 single Palmaz-Schatz stents and 347 atherectomies, 367 (82%) of which had repeat angiographic measurement 6 months after intervention. Atherectomy-treated lesions had a higher proportion of left anterior descending to right coronary arteries (68 vs 24%) compared with stents (31 vs 54%), p < 0.001. Although subsequent restenosis rates were similar for stenting (25%) and atherectomy (30%, p = 0.42), left anterior descending versus right coronary lesions had a significantly higher restenosis rate for the overall group (35 vs 18%, p = 0.009), for stents (44 vs 13%, p = 0.008) and for atherectomy (35 vs 22%, p = 0.10), respectively. Multivariable analysis demonstrated that postprocedure luminal diameter (p = 0.03, p = 0.009) and coronary location (the proportion of left anterior descending vessels treated, p = 0.002, p < 0.001), but not device type (stent vs atherectomy), were strong independent determinants of restenosis according to both binary (> 50% diameter stenosis) and continuous (late percent stenosis) definitions.(ABSTRACT TRUNCATED AT 250 WORDS)


Detection of silent coronary artery disease in adolescents and young adults with familial hypercholesterolemia by single-photon emission computed tomography thallium-201 scanning. Familial hypercholesterolemia (FH), a genetic disease characterized by increased levels of total and low-density lipoprotein cholesterol in the blood, results in a markedly increased incidence of atherosclerosis and coronary artery disease in homozygotes and to a lesser extent in heterozygotes. The purpose of this study was to detect the presence of myocardial ischemia, particularly in heterozygotes, with stress single-photon emission computed tomography thallium-201 scanning and to determine if there were any differentiating variables between heterozygotes with normal and abnormal thallium-201 scans. Fifty-four patients (mean age 16 years; range 8 to 24) with FH were analyzed (4 homozygotes and 50 heterozygotes). Eleven heterozygotes and 3 homozygotes had abnormal thallium-201 scans. Family history, lipid profile, age and sex of heterozygotes with FH did not predict the presence of myocardial ischemia. The mean total cholesterol level in heterozygotes with normal thallium-201 scans was 7.68 +/- 2.29 mmol/liter (297 mg/dl), which was not significantly different from that in heterozygotes with abnormal scans (7.63 +/- 1.07 mmol/liter [295 mg/dl]; p = 0.91). The coronary angiography of 1 homozygote who had an abnormal thallium-201 scan demonstrated a 50% stenosis of the left anterior descending artery. Aggressive, repetitive plasma exchange was then instituted. The 11 heterozygotes with abnormal thallium-201 scans underwent more rigorous dietary and drug therapy. It is concluded that myocardial ischemia with stress in heterozygotes with FH can occur at a young age and that thallium-201 scanning should be performed early as a screening test and to guide patient management.


Changing circadian variation of transient myocardial ischemia during the first year after a first acute myocardial infarction. In a consecutive series of 123 men (aged 55 +/- 8 years) with a recent first acute myocardial infarction (AMI), 24-hour ambulatory ST-segment monitoring was performed early after discharge (day 11 +/- 5), 6 months (day 185 +/- 6) and 1 year (day 368 +/- 8) after AMI. No difference in the prevalence of transient myocardial ischemia was found between the 3 recordings (17, 17 and 20%), and most ischemic episodes were silent (98, 100 and 97%). In the early postinfarction period, a peak of ischemic activity was demonstrated between 6 P.M. and midnight (40 of 93 episodes [43%]). Over time, the maximal occurrence of ischemia gradually advanced toward the morning hours with a peak activity between 6 A.M. and noon at 1-year follow-up (32 of 73 episodes [44%]). Significantly more patients (16 of 21 [76%]) had ischemia from 6 P.M. to midnight at discharge compared with the findings 1 year later (9 of 23 patients [39%]) (p < 0.03). An opposite trend was found regarding patients who exhibited ischemic episodes in the hours from 6 A.M. to noon: 10 of 21 patients (48%) early after discharge versus 17 of 23 patients (74%) at 1-year follow-up (p = not significant). Results from the 6-month recording displayed characteristics between the findings from discharge and 1-year ambulatory monitoring. The pathophysiologic processes underlying the observations from this study are unknown. The change in circadian periodicity could not be explained from differences in heart rate variation patterns or medical antianginal treatment among the 3 recordings.(ABSTRACT TRUNCATED AT 250 WORDS)


Usefulness of heavy isometric exercise echocardiography for assessing left ventricular wall motion patterns late (> or = 6 months) after acute myocardial infarction. The aim of this prospective study was to determine the effects of heavy isometric exercise on left ventricular (LV) wall motion patterns in patients who have had myocardial infarction, and to compare heavy isometric exercise with dynamic exercise for competence in eliciting LV wall motion abnormalities at equivalent rate-pressure products. Echocardiography was performed in 42 patients during supine bicycle ergometry and during heavy dynamometer stretching at 50% of maximal voluntary contraction. Systemic vascular resistance increased from 1,484 to 1,649 dynes s cm-5 (p < 0.05) during isometric exercise, and decreased significantly during dynamic exercise. Wall motion abnormalities or new asynergy were induced by isometric exercise in 120 segments, 107 of which (89%) showed significant stenosis of the perfusing coronary artery. Hypokinesia was the dominant pattern in the range of 76 to 90% narrowing; akinesia was dominant at 91 to 100% narrowing. Wall motion abnormalities were also documented in 13 segments (11%) assumed to be supplied by vessels with nonsignificant stenosis. Dyskinesia, seen in 7% of the segments, was equally distributed between both groups with significant stenosis. Sensitivity and positive predictive value in identifying specific coronary vessel disease was similar for both isometric and dynamic exercise. In conclusion, heavy isometric exercise in patients who have had myocardial infarction induces wall motion abnormalities of a severity proportional to the degree of coronary narrowing. This exercise method is similar to dynamic exercise for ability in identifying obstructions in a specific vessel. Furthermore, when compared at near-equal rate-pressure products, heavy isometric exercise is far superior in sensitivity to dynamic exercise.


Patterns of myoglobin and MM creatine kinase isoforms release early after intravenous thrombolysis or direct percutaneous transluminal coronary angioplasty for acute myocardial infarction, and implications for the early noninvasive diagnosis of reperfusion. Early noninvasive detection of reperfusion after thrombolysis for acute myocardial infarction may enable detection of unsuccessful thrombolysis in time for rescue percutaneous transluminal coronary angioplasty (PTCA). It has been suggested that repeated measurement of myoglobin or of MM creatine kinase (CK) isoforms enables early detection of reperfusion. Twenty consecutive patients with acute myocardial infarction treated by intravenous thrombolysis underwent serial determination of myoglobin, MM3 and MM1 CK isoforms every 30 minutes after the beginning of thrombolysis. At 90 minutes, coronary angiography was performed, enabling classification of patients as with (group A) and without (group B) reperfusion. A third group of 7 patients (group C) underwent direct PTCA without antecedent thrombolysis. In all groups, there were increases in myoglobin, percentage of MM3 isoform, and ratio of MM3/MM1. These increases appeared on the average steeper and faster in group B, but the large dispersion of values in this group resulted in a wide overlap with group A. Retrospective analysis suggests that an increase in the MM3/MM1 ratio > 0.35 after 60 minutes is very specific for reperfusion (sensitivity 60% and specificity 100%). In group C, PTCA always led to a sharp increase in all biochemical parameters measured within 30 minutes. Thus, macromolecular markers can be used for very early, noninvasive detection of reperfusion with a high specificity. This could help reduce the need for emergency angiography to select candidates for rescue PTCA. Furthermore, the patterns of biochemical markers of reperfusion differ when reperfusion is initiated by either thrombolysis or PTCA.


Relation of body fat distribution in men and degree of coronary narrowings in coronary artery disease. This study evaluates the relation between body fat distribution and severity of coronary artery disease (CAD). The study sample comprised 33 patients with angiographically demonstrated CAD and 10 angiographically normal control subjects. Body fat distribution was estimated by computed tomography and degree of coronary narrowings by angiographic score. Body weight, body mass index and total and subcutaneous abdominal adipose tissue areas showed no statistical differences in the 2 groups; visceral abdominal adipose tissue area and the visceral to subcutaneous abdominal adipose tissue area ratio were significantly higher in patients with CAD (p < 0.05). There was a significant correlation between visceral fat and triglycerides, apoprotein B and sum of glucose and insulin during glucose oral tolerance test. Sum of insulin during glucose oral tolerance test, visceral abdominal adipose tissue area and visceral/subcutaneous abdominal adipose tissue area ratio correlated significantly with severity of CAD, as evaluated by coronary score in all subjects and in CAD patients alone. Stepwise multiple regression analysis using the coronary score as the dependent variable and anthropometric and metabolic parameters as independent variables shows that in all subjects and in CAD patients alone, visceral/subcutaneous abdominal adipose-tissue area ratio entered the regression first and the sum of insulin during glucose oral tolerance test second. The results suggest that visceral abdominal adipose tissue area and visceral to subcutaneous abdominal adipose tissue area ratio may be cardiovascular risk factors.


Beat-to-beat morphologic variability of the electrocardiogram for the evaluation of chest pain in the emergency room. The value of electrocardiographic, morphologic variability in the early diagnosis of acute myocardial infarction (AMI) and myocardial ischemia was evaluated in 49 nonselected patients presenting to the emergency room with chest pain. High-resolution electrocardiography was used to determine the morphologic variability of consecutive electrocardiographic complexes, and the ratio of the variance of the QRS onset to that of the entire electrocardiogram was calculated. A final diagnosis of AMI was confirmed in 8 patients, acute coronary insufficiency in 8, angina pectoris in 19, and a noncardiac origin for chest pain in 14. Patients with AMI had a significantly higher beat-to-beat electrocardiographic morphologic variability of the QRS onset (1.4 +/- 0.2) than did those with acute coronary insufficiency (1.1 +/- 0.2), angina pectoris (0.9 +/- 0.1) or noncardiac chest pain (0.8 +/- 0.1) (p < 0.05). The sensitivity of the clinical presentation, typical electrocardiographic changes and creatine phosphokinase levels for the diagnosis of an acute ischemic event on admission to the emergency room was 62, 25 and 37.5%, respectively. Relative variance of the QRS onset of > 0.86 had a sensitivity of 75% and a specificity of 61% for diagnosing an acute ischemic event. Logistic regression of these variables showed that the QRS onset relative variability is an independent predictor for an acute ischemic event. It is concluded that an increased beat-to-beat electrocardiographic variability in patients with AMI is present on admission to the emergency room and may assist in establishing the diagnosis in this setting.


Degrees of coronary arterial narrowing at necropsy in men with large fusiform abdominal aortic aneurysm. In 27 patients (mean age at death 72 +/- 9 years) with abdominal aortic aneurysm (AAA) > or = 5.0 cm in its widest transverse diameter, the amounts of narrowing at necropsy in the 4 major (left main, left anterior descending, left circumflex, and right) epicardial coronary arteries were determined. During life, 12 of the 27 patients (44%) had symptoms of myocardial ischemia: angina pectoris alone in 2, acute myocardial infarction alone in 3, angina pectoris and acute myocardial infarction in 5, and sudden coronary death in 2. Ten of the 27 patients (37%) died from consequences of myocardial ischemia. Six (22%) died from rupture of the AAA. Grossly visible left ventricular necrosis or fibrosis, or both, was present in 15 patients (56%). Of the 27 patients, 23 (85%) had narrowing 76 to 100% in cross-sectional area of 1 or more major coronary arteries by atherosclerotic plaque. The mean number of coronary arteries per patient severely (> 75%) narrowed was 2.0 +/- 1.3/4.0. Of the 108 major coronary arteries in the 27 patients, 55 (51%) were narrowed > 75% in cross-sectional area by plaque. The 4 major coronary arteries in the 27 patients were divided into 5-mm segments and a histologic section, stained by the Movat method, was prepared from each segment. The mean percentages of the resulting 1,475 five-mm segments narrowed in cross-sectional area 0 to 25%, 26 to 50%, 51 to 75%, 76 to 95% and 96 to 100% were 17, 37, 28, 15 and 3%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


Amounts of coronary arterial narrowing by atherosclerotic plaque at necropsy in patients with lower extremity amputation. In 26 patients (mean age at death 68 +/- 9 years) who had undergone amputation (at mean age 63 +/- 12 years) of 1 or both lower extremities due to severe peripheral arterial atherosclerosis, the amounts of narrowing at necropsy in the 4 major (left main, left anterior descending, left circumflex, and right) epicardial coronary arteries were determined. During life, 15 of the 26 patients (58%) had symptoms of myocardial ischemia: angina pectoris alone in 1, acute myocardial infarction alone in 5, and angina and/or infarction plus congestive heart failure or sudden coronary death in 9. Twelve of the 26 patients (42%) died from consequences of myocardial ischemia: acute myocardial infarction in 5, sudden coronary death in 3, chronic congestive heart failure in 3, and shortly after coronary bypass surgery in 1. Grossly visible left ventricular necrosis or fibrosis, or both, was present in 21 patients (81%). Of the 26 patients, 24 (92%) had narrowing 76 to 100% in cross-sectional area of 1 or more major coronary arteries by atherosclerotic plaque. The mean number of coronary arteries per patient severely (> 75%) narrowed was 2.3 +/- 1.0/4.0. Of the 104 major coronary arteries in the 26 patients, 60 (58%) were narrowed > 75% in cross-sectional area by plaque. The 4 major coronary arteries in the 26 patients were divided into 5-mm segments and a histologic section, stained by the Movat method, was prepared from each segment.(ABSTRACT TRUNCATED AT 250 WORDS)


Morphologic characterization and quantitative assessment of mitral regurgitation with ruptured chordae tendineae by transesophageal echocardiography. To compare the accuracy of transesophageal echocardiography (TEE) with that of transthoracic echocardiography (TTE) in the detection of morphologic characteristics and in the quantitative assessment of the severity of mitral regurgitation with ruptured chordae tendineae, 40 patients with ruptured chordae tendineae (group 1) and 20 patients with moderate or severe mitral regurgitation due to other causes (group 2) were studied. All echocardiograms were recorded before cardiac surgery. Cardiac catheterization was performed in 55 patients (92%). TEE showed greater sensitivity and negative predictive value than TTE (100 vs 65%, and 100 vs 56%, respectively; p < 0.005) in the diagnosis of ruptured chordae tendineae. Visualization of the ruptured chordae (termed snake-tongue sign) was highly sensitive and specific (93 and 95%, respectively) for establishing the diagnosis of ruptured chordae tendineae. The severity of mitral regurgitation in group 1 patients evaluated by TTE color flow mapping was underestimated by 2 grades in 1 patient and by 1 grade in 6 patients, and overestimated by 1 grade in 1 patient, compared with left ventriculography. In contrast, by TEE color flow mapping it was underestimated by 1 grade in 1 and overestimated by 1 grade in 1 patient. TEE color flow mapping showed better correlation with angiography than did TTE color flow mapping (r = 0.82 vs r = 0.49).


Long-term echocardiographic Doppler monitoring of Hancock bioprostheses in the mitral valve position. Echocardiographic and Doppler studies were performed in 134 patients with a Hancock bioprosthesis in the mitral valve position during a follow-up period of 1 to 216 months. Among the xenografts, 57% were clinically normal and 43% had severe dysfunction. Among the normal bioprostheses, 35% had echocardiographically thickened mitral cusps (> or = 3 mm) with normal hemodynamic function; by setting the lower 95% confidence limit of valve area at 1.7 cm2 these patients had a significantly (p < 0.01) smaller valve area than that of normal control subjects. Evaluation of all thickened normal mitral valves showed the highest incidence of thickening at 9 years after implantation. Valve replacement surgery was subsequently performed in 33 patients with dysfunctioning bioprosthetic and echocardiographic diagnosis was confirmed in 91% of explanted valves (bioprosthetic stenosis 21%, incompetence 46%, and combined stenosis and regurgitation 33%). In 2 valves that were found to be stenotic on echocardiographic examination, a calcium-related commissural tear was also observed at reoperation, and in another, a paravalvular leak was found. Dystrophic calcification, isolated (64%) or occasionally associated with fibrous tissue overgrowth (21%), was the main cause of failure. Pannus was present in prostheses with longer satisfactory function (168 +/- 31 vs 124 +/- 21 months; p < 0.001). Long-term performance was evaluated by the Kaplan-Meier method for up to 18 years of follow-up. Freedom from structural valvular disfunction after mitral replacement was 89% at 6 years, 77% at 8 years, 56% at 10 years, 31% at 12 years, 16% at 15 years, and 15% at 18 years.


A new, noninvasive method to monitor the aging of bioprosthetic valves in the mitral position. Bioprosthetic valves undergo a tissue degeneration of unpredictable onset and amount. This process alters the structure and function of the valve and consequently shortens its lifespan. The echocardiographic technique usually used in the follow-up of these patients does not provide accurate information concerning the amount of prosthesis tissue degeneration. A new technique has been developed based on the spectral analysis of the first heart sound, which enables the evaluation of prosthetic leaflet stiffness. The Young's modulus (E) and stress (s) of the valve leaflets were derived as functions of the inner diameter of the heterograft and its primary vibration frequency, which can be obtained from the frequency spectrum of the first heart sound. Thirty-six patients with a mitral bioprosthetic valve were studied. Fifteen had thickening or calcification, or both, of the valvular leaflets at echocardiographic examination. In patients with a normal valve, E and s showed a good correlation with the duration of implantation (r = 0.909, p < 0.001; and r = 0.828, p < 0.001; respectively). Patients with abnormal leaflets had values of E and s that were greater than the theoretical values expected for their duration of implantation. The procedure is sensitive, accurate and easy to perform, and enables monitoring of the aging of the prosthetic valve and early identification of valve tissue degeneration. Together with echocardiography, this procedure yields a more complete evaluation of prosthetic valves for the follow-up of patients.


Predictors, mechanisms and outcome of severe mitral regurgitation complicating percutaneous mitral valvotomy with the Inoue balloon. During 241 consecutive percutaneous mitral valvotomy (PMV) procedures performed with the Inoue balloon, 16 patients (6.6%) developed severe mitral regurgitation (MR). Baseline clinical, echocardiographic (Doppler mitral valve area and Wilkins' score) and hemodynamic data were not different from those of patients without this complication. Severe MR occurred during the first inflation in 7 patients and after several stepwise inflations in 9. Although maximal balloon size was similar in both groups, unusual indentations and subvalvular inflations were more frequently observed in patients who developed severe MR. Early mitral valve replacement was required in 6 patients. All of them had a leaflet rupture either along the midportion (2 patients), along a commissure (4 patients), or both. Commissural calcium was present in 5 valves and 5 also had severe subvalvular involvement that had been underestimated by echocardiography. Of the 10 nonsurgically treated patients, 4 had chordal rupture by echocardiographic criteria, whereas in the remaining 6 the precise mechanism of MR could not be determined. During follow-up (11.4 +/- 4 months, range 1 to 30), 1 patient required surgery for symptoms and the remaining 9 were symptomatically improved and free of left ventricular dilatation. In conclusion, severe MR complicated 6.6% of PMV procedures with the Inoue balloon, and its mechanism was leaflet or chordal rupture. Although one third of the patients required early mitral surgery, most of the remaining obtained midterm symptomatic benefit.


Effects of dobutamine on Gorlin and continuity equation valve areas and valve resistance in valvular aortic stenosis. Previous studies demonstrated changes in aortic valve area calculated by the Gorlin equation under conditions of varying transvalvular flow in patients with valvular aortic stenosis (AS). To distinguish between flow-dependence of the Gorlin formula and changes in actual orifice area, the Gorlin valve area and 2 other measures of severity of AS, continuity equation valve area and valve resistance, were calculated under 2 flow conditions in 12 patients with AS. Transvalvular flow rate was varied by administration of dobutamine. During dobutamine infusion, right atrial and left ventricular end-diastolic pressures decreased, left ventricular peak systolic pressure and stroke volume increased, and systolic arterial pressure did not change. Heart rate increased by 19%, cardiac output by 38% and mean aortic valve gradient by 25%. The Gorlin valve area increased in all 12 patients by 0.03 to 0.30 cm2. The average Gorlin valve area increased from 0.67 +/- 0.05 to 0.79 +/- 0.06 cm2 (p < 0.001). In contrast, the continuity equation valve area (calculated in a subset of 6 patients) and valve resistance did not change with dobutamine. The data support the conclusion that flow-dependence of the Gorlin aortic valve area, rather than an increase in actual orifice area, is responsible for the finding that greater valve areas are calculated at greater transvalvular flow rates. Valve resistance is a less flow-dependent means of assessing severity of AS.


Prognostic implications of subclinical left ventricular dilatation and systolic dysfunction in men free of overt cardiovascular disease (the Framingham Heart Study). To determine the prognostic significance of asymptomatic left ventricular (LV) dilatation and LV systolic dysfunction, 1,493 men who were free of symptomatic cardiovascular disease underwent M-mode echocardiography and were then followed for a mean of 4.15 years. At baseline examination, 170 men (11.4%) had an abnormally high end-diastolic LV internal dimension (> or = 56 mm) and 76 (5.1%) had an abnormally low fractional shortening (< or = 30%). During the follow-up period, 68 men experienced 92 cardiovascular disease events. After adjusting for age and traditional cardiovascular disease risk factors in proportional-hazards analyses, fractional shortening was a significant independent predictor of cardiovascular risk (relative risk [RR] = 1.42, 95% confidence interval [CI] 1.12 to 1.81, for decrease of fractional shortening by 4%). Increased risk was also associated with combinations of low fractional shortening and high end-diastolic internal dimension (RR = 3.77, 95% CI 1.59 to 8.93) and with low percent fractional shortening with LV hypertrophy (RR = 5.93, 95% CI 1.97 to 17.85). In conclusion, subclinical LV dilatation and LV systolic dysfunction, although uncommon in men free of overt cardiovascular disease, are associated with increased risk for new cardiovascular disease events.


Left ventricular filling abnormalities in non-insulin-dependent diabetes mellitus and improvement by a short-term glycemic control. To determine whether left ventricular (LV) filling abnormalities in diabetes are associated with diabetic microangiopathy, and to evaluate the effect of a short-term glycemic control on the filling abnormalities, diastolic filling dynamics were assessed by pulsed Doppler echocardiography in 246 patients with non-insulin-dependent diabetics. Isovolumic relaxation time and the ratio of peak flow velocity of atrial filling wave to peak flow velocity of early filling wave (A/E) were significantly greater in diabetic patients than in age- and sex-matched control subjects. Diabetic patients with retinopathy had significantly greater isovolumic relaxation time and A/E values than those without retinopathy. A/E was significantly decreased 1 month after insulin treatment in those without, but not with retinopathy. It is concluded that LV diastolic filling is impaired in mildly hyperglycemic patients with non-insulin-dependent diabetes mellitus without severe complications, the abnormality being more intense in patients with retinopathy. A short-term glycemic control results in a marked decrease in abnormalities in patients without, but not with retinopathy.


Age-related increase in systolic fraction of pulmonary vein flow velocity-time integral from transesophageal Doppler echocardiography in subjects without cardiac disease. The pulmonary vein flow velocity-time profile would be equivalent to the pulmonary vein flow volume-time profile, provided that the cross-sectional area of the pulmonary vein remains unchanged during 1 cardiac cycle. The systolic fraction of the pulmonary vein flow velocity-time integral, a ratio of velocity-time integral of the S wave to the sum of velocity-time integrals of the S and D waves, represents the ratio of left atrial storage volume to left ventricular stroke volume. This systolic fraction may help early filling of the left ventricle through an appropriate storage of blood and generation of driving pressure in the left atrium. Because early filling of the left ventricle is progressively impaired with age, it was hypothesized that this systolic fraction is increased with age. Forty-four noncardiac surgical patients (age range 17 to 70 years) who underwent transesophageal Doppler echocardiography under general anesthesia were studied, and left upper pulmonary vein flow and mitral inflow velocities were recorded. The ratio of peak velocity of the E wave to that of the A wave of mitral inflow velocity-time profile (y) decreased with age (y = -0.0245 x age + 2.41; r = -0.672, p < 0.01). Systolic fraction (y) increased with age (y = 0.00373 x age + 0.514; r = 0.656, p < 0.01). The age-related increase in the systolic fraction of pulmonary vein flow velocity-time integral may account for the compensation for impaired early filling of the left ventricle in elderly patients.


Frequency of long-term lower limb ischemia associated with intraaortic balloon pump use. Lower limb ischemia is a frequent complication of intraaortic balloon pump (IABP) use. The incidence and risk factors for acute ischemia have been well-defined, but little is known about long-term ischemic complications. This prospective study evaluated the incidence, nature, progression and predisposing factors for long-term lower limb ischemia in 151 patients who were previously treated with the IABP. These persons were interviewed and their lower extremities examined 12 to 20 months after undergoing IABP counterpulsation. Limb ischemia, characterized primarily by ipsilateral discomfort and diminished pulses, occurred in 18% of those evaluated. Evidence of ischemia worsened over time in 14%. Logistic regression analysis, which was based on variables found to be significant in bivariate analysis, revealed that the occurrence of limb ischemia acutely, cardiogenic shock as an indication for IABP insertion, and smoking (at the time of hospitalization or having quit < 10 years previously) were risk factors for long-term lower limb ischemia. The adjusted odds ratio for acute limb ischemia was 8.89 (95% confidence interval 2.80 to 28.21), for cardiogenic shock 3.59 (95% confidence interval 1.01 to 12.75), and for smoking 2.87 (95% confidence interval 1.10 to 7.46). Increasing numbers of patients are undergoing IABP counterpulsation and a greater proportion of these are surviving their acute event and resuming active lives. It is essential to recognize that detrimental consequences of this device can persist long after hospitalization.


Automated, on-line quantification of left ventricular dimensions and function by echocardiography with backscatter imaging and lateral gain compensation. To provide on-line quantification of left ventricular cavity dimensions and function by echocardiography 60 control subjects and 10 patients with cardiac dysfunction were studied. A novel, ultrasound imaging system was used which was developed to detect and track, in real time, ventricular endocardial blood boundaries based on quantitative assessment of acoustic properties of tissue. In addition, lateral gain compensation, a robust and novel image enhancement procedure, was used to provide instantaneous measurement and display of cavity areas and functional indexes on a beat-by-beat basis within regions of interest drawn around the blood pool cavity. In control subjects, short-axis end-diastolic area averaged 13.1 +/- 3.7 cm2 (SD), end-systolic area 5.9 +/- 2.7 cm2, and fractional area change 55.6 +/- 11.2%. Apical views yielded corresponding values of 23.8 +/- 4.5 cm2, 15.5 +/- 3.4 cm2 and 34.7 +/- 7.8%. Instantaneous peak rate of cavity area change approximated 50 cm2/s in systole and 60 cm2/s in diastole in each view. Serial measurements of area and functional index were reproducible over intervals of 2 to 3 weeks. Patients with dilated ventricles exhibited average apical view area values of 49.1 +/- 6.1 cm2 and 43.1 +/- 4.9 cm2 in diastole and systole with a fractional area change of 12.2 +/- 3.0%. Thus, results with on-line echocardiographic backscatter imaging-assisted automated edge detection are reproducible and capable of delineating cardiac dysfunction conveniently, promptly and serially at the bedside.


Creatinine arm index as alternative for creatinine height index. Nutritional assessment of elderly people is limited due to a lack of age-corrected standards. The objective of this study was to develop a new, more age-independent index for nutritional assessment by correcting the creatinine height index (CHI) for the age-induced changes in its variables. This might improve the differentiation between physiological reduction in muscle mass in elderly people and the changes induced by malnutrition. Seventy-four elderly and 100 young healthy volunteers were compared by anthropometric and biochemical-assessment variables. From the high correlation between total arm length and body length (r = 0.86; P less than 0.001) and the use of an alternative formula to calculate ideal body weight (IBW) from height and wrist circumference, a relatively age-independent estimate of IBW was determined. Creatinine arm index, as an adapted index of CHI, is proposed based on this age-independent IBW estimation and a specific creatinine coefficient for different age groups.


Dietary fat and body fat: a multivariate study of 205 adult females. This study examined the association between diet composition, particularly dietary fat intake, and body-fat percentage in 205 adult females. Subjects completed a written questionnaire regarding lifestyle factors, such as exercise participation and smoking, demographic data, and the diet section of the National Cancer Institute's Health Habits and History Questionnaire by Block. Skinfold-thickness measures were used to ascertain the body-fat percentage of each subject. Results showed that intake of dietary fat was related significantly with adiposity, without (F = 13.65, R2 = 0.063, P = 0.0003) and with (F = 8.74, R2 = 0.033, P = 0.0035) control for multiple potential confounding factors: age, total energy intake, total exercise time per week, years of regular physical activity, consumption of other macronutrients, and smoking. Unlike dietary fat intake, protein consumption and carbohydrate intake were not significant individual predictors of body-fat percentage when the potential confounding variables were controlled. The findings suggest that dietary fat intake may play a role in obesity beyond dietary energy content.


Basal metabolic rate of Colombian children 2-16 y of age: ethnicity and nutritional status. Measurements of basal metabolic rate (BMR) were made in 528 children 2-16 y of age living in underprivileged areas of the city of Cali, Colombia (153 control and 186 undernourished boys, 93 control and 96 undernourished girls). The data are related to BMR calculated from the equations of Schofield and to estimates of the lean body mass (LBM). The ethnic composition of the subjects was 80% mestizo (mixed European and South Amerindian ancestry), 15% black, and 5% white. The data do not show any variations due to race in these subjects. The Schofield equations overestimate the BMR of boys by approximately 6% whereas the estimation of BMR in girls is not significantly different from measured values. More than 65% of the variation in BMR of both nutritionally normal and undernourished boys and girls is explained by variation in body size as estimated by the LBM.


Body composition, energy utilization, and nitrogen metabolism with a 4.25-MJ/d low-energy diet supplemented with pyruvate. We measured body composition, energy deficit, and nitrogen metabolism in 14 obese women housed in a metabolic ward, who consumed a 4.25-MJ/d liquid diet (68% carbohydrate, 22% protein) for 21 d with or without pyruvate (PY; n = 7) partially, isoenergetically substituted for glucose (placebo; n = 7). Body composition and leucine oxidation and turnover were determined before and after weight loss. Energy deficit was calculated from resting metabolic rates. Subjects fed pyruvate showed a greater weight loss (PY = 5.9 +/- 0.7 kg, placebo = 4.3 +/- 0.3 kg, P less than 0.05), fat loss (PY = 4.0 +/- 0.5 kg, placebo = 2.7 +/- 0.2 kg, P less than 0.05), kg wt loss/4.25-MJ deficit (PY = 0.22 +/- 0.01 kg, placebo = 0.17 +/- 0.01 kg, P less than 0.05, and kg fat loss/4.25-MJ deficit (PY = 0.15 +/- 0.01 kg, placebo = 0.11 +/- 0.01 kg, P less than 0.05). Nitrogen balance (urine and stool) and leucine oxidation and turnover were similar in both groups. We conclude that the dietary modification whereby the three-carbon compound pyruvate is isoenergetically substituted for the six-carbon compound glucose in a 4.25-MJ/d, low-energy diet will increase fat and weight loss.


Body composition, nitrogen metabolism, and energy utilization with feeding of mildly restricted (4.2 MJ/d) and severely restricted (2.1 MJ/d) isonitrogenous diets. To determine the effects on weight loss of feeding isonitrogenous diets in mildly restricted (4.2 MJ/d) and severely restricted (2.1 MJ/d) amounts, we measured body composition, weight loss-energy deficit ratio, and nitrogen metabolism in 14 obese women housed in a metabolic ward consuming hypoenergetic diets for 21 d. Subjects consumed either a 4.2-MJ/d diet (50 g protein, 175 g carbohydrate) or a 2.1-MJ/d diet (50 g protein, 75 g carbohydrate). Body composition and leucine oxidation and turnover were determined before and after weight loss. Energy deficit was calculated from resting metabolic rates. Subjects fed the 2.1-MJ/d diet showed a greater weight loss (6.1 +/- 0.5 vs 4.5 +/- 0.5 kg; mean +/- SE, P less than 0.05) and fat loss (3.9 +/- 0.3 vs 3.0 +/- 0.3 kg, P less than 0.05). Weight loss-energy deficit ratio was the same with both diets. Nitrogen balance and leucine oxidation and turnover were similar in both groups. We conclude that with feeding of isonitrogenous hypoenergetic diets, severe restriction of energy content (2.1 MJ/d, 75 g carbohydrate) will enhance weight and fat loss without increasing nitrogen loss compared with mild restriction of energy (4.2 MJ/d).


Metabolic response to experimental overfeeding in lean and overweight healthy volunteers. Possible adaptive mechanisms that may defend against weight gain during periods of excessive energy intake were investigated by overfeeding six lean and three overweight young men by 50% above baseline requirements with a mixed diet for 42 d [6.2 +/- 1.9 MJ/d (mean +/- SD), or a total of 265 +/- 45 MJ]. Mean weight gain was 7.6 +/- 1.6 kg (58 +/- 18% fat). The energy cost of tissue deposition (28.7 +/- 4.4 MJ/kg) matched the theoretical cost (26.0 MJ/kg). Basal metabolic rate (BMR) increased by 0.9 +/- 0.4 MJ/d and daily energy expenditure assessed by whole-body calorimetry (CAL EE) increased by 1.8 +/- 0.5 MJ/d. Total free-living energy expenditure (TEE) measured by doubly labeled water increased by 1.4 +/- 2.0 MJ/d. Activity and thermogenesis (computed as CAL EE--BMR and TEE--BMR) increased by only 0.9 +/- 0.4 and 0.9 +/- 2.1 MJ/d, respectively. All outcomes were consistent with theoretical changes due to the increased fat-free mass, body weight, and energy intake. There was no evidence of any active energy-dissipating mechanisms.


Gastric capacity, gastric emptying, and test-meal intake in normal and bulimic women. The role of the stomach in regulating appetite in bulimia nervosa was examined. Subjects were nine normal and nine bulimic women of similar age, height, and weight. Gastric capacity was estimated by filling a balloon in the stomach. The mean stomach capacity of bulimic subjects was significantly larger than that of normal subjects, as revealed by the larger balloon volume tolerated (P less than 0.01) and by the larger volume needed to produce a 5 cm H2O increase in intragastric pressure (P = 0.07). The intake of a liquid meal was also significantly larger for the bulimic subjects. Gastric-emptying rate of a liquid meal was significantly delayed in the bulimic subjects during the initial 5-15 min. In all subjects, test-meal intake correlated significantly with gastric capacity (r = 0.53). In the bulimic subjects, self-reported binge intake (J) also correlated significantly with gastric capacity (r = 0.75). Binge eating in bulimic subjects may enlarge gastric capacity, which could then promote even larger binges through positive feedback.


A 24-h energy expenditure study on reduced-obese and nonobese women: effect of beta-blockade. Twenty-four-hour energy expenditure (EE) and substrate oxidation rates were studied in a respiration chamber in 15 reduced-obese (BMI = 24.7) and 8 nonobese (BMI = 20.1) women. Two experiments were performed, one in which beta-blockade was introduced by propranolol and one with placebo. When adjusted for differences in fat-free mass, no difference in 24-h EE was found between the reduced-obese and nonobese groups in placebo experiments. Propranolol reduced 24-h EE by 2.7% in the reduced-obese group whereas no reduction was seen in the nonobese group. A positive correlation was found between fasting glycerol concentration and lipid oxidation. During daytime, lipid oxidation was reduced and carbohydrate oxidation increased by propranolol only in the nonobese subjects. Propranolol reduced fasting glycerol and free fatty acid concentrations in both groups. Beta-blockade seems to have little effect on sedentary 24-h EE but may have a suppressing effect on lipid combustion.


Comparison of the effects on lipoproteins and apolipoproteins of a diet high in monounsaturated fatty acids, enriched with avocado, and a high-carbohydrate diet. A randomized trial was conducted to compare effects of a diet high in monounsaturated fatty acids, enriched with avocado (AE), and a high-complex-carbohydrate diet (AHA-III) on blood lipid concentrations. Fifteen females between 37 and 58 y of age were allocated either to AE followed by AHA-III, or vice versa. Each dietary phase lasted 3 wk. Both diets were found to lower total cholesterol compared with baseline values. AE was more effective, with an 8.2% decrease (P less than 0.05) whereas AHA-III was associated with a 4.9% decrease (NS). Low-density-lipoprotein cholesterol and apolipoprotein B decreased significantly on AE but not on AHA-III (P less than 0.05). The high-density-lipoprotein (HDL) concentration did not change on AE but decreased 13.9% on AHA-III (P less than 0.01). It is concluded that AE is more effective than is AHA-III in decreasing total cholesterol, and, unlike AHA-III, it does not decrease HDL concentrations.


Comparative effects of a recommended lipid-lowering diet vs a diet rich in monounsaturated fatty acids on serum lipid profiles in healthy young adults. This crossover study investigated the effects of two fat-reduced diets, one rich in monounsaturated fatty acids (MUFAs), the other rich in polyunsaturated fatty acids (PUFAs), on serum lipid profiles in 38 healthy young adults initially on a typical western diet. After being randomly assigned to two groups, the subjects received the MUFA or PUFA diet for 3-wk and then the other diet for 3 wk. Both test diets led to significant reductions in serum cholesterol, LDL cholesterol, and HDL cholesterol (P less than 0.001). Both reduced apolipoprotein B (P less than 0.001) and apolipoprotein A-I concentrations (P less than 0.01 for the MUFA, P less than 0.001 for the PUFA diet). Apolipoprotein A-I was significantly higher on the MUFA than on the PUFA diet. The ratio of apolipoprotein A-I to B significantly increased on both diets. Thus, a low-fat, MUFA-rich diet is as effective as a low-fat, PUFA-rich diet in lowering total and LDL cholesterol, but both also lowered HDL cholesterol concentrations. The MUFA-rich diet may be more advantageous than the PUFA-rich one because it does not lower apolipoprotein A-I concentrations as much as the PUFA-rich diet.


Effect of beta-carotene supplementation on photosuppression of delayed-type hypersensitivity in normal young men. The aim of this study was to examine whether beta-carotene protects against the immunosuppression seen with long-wave ultraviolet-light (UV-A) exposure. Free-living, healthy men, aged 19-39 y received 30 mg beta-carotene/d or a placebo while on a single-menu, low-carotenoid diet. After 28 d all subjects received 12 exposures to a UV-A/B light source over a 16-d period. The total UV-A dose received ranged from 15.9 to 19.3 J/cm2. The total shorter-wave ultraviolet-light (UV-B) dose varied from 1.59 to 1.96 J/cm2. Follow-up continued for 21 d. Carotenoid assays and delayed-type hypersensitivity (DTH) tests were performed at baseline, pre-UV, post-UV, and after follow-up. The DTH-test responses were significantly suppressed in the placebo group after UV treatments. The suppression was inversely related to plasma beta-carotene concentrations in this group. There was no significant suppression of DTH test responses in the beta-carotene group. It is concluded that beta-carotene protects against photosuppression of immune function.


Prediction of iron absorption based on iron status of female blood donors. Iron stores were assessed in 27 postmenopausal healthy women who donated five units of blood (approximately 485 mL/unit) over approximately 1 y. The mean (+/- SD) age was 67.7 +/- 4.0 y and the average time between successive blood donations was approximately 10 wk (range 8-30 wk). Steady-state iron stores at entrance were 10.59 +/- 3.88 mg/kg body wt (mean +/- SD) and declined to 1.03 +/- 3.20 mg/kg by the fifth donation. Determination of iron stores was based on biochemical measures of iron status at each donation. Iron intakes were 23.3 +/- 10.1 mg/d. From these data we developed equations that can be used to predict the frequency at which healthy postmenopausal women can donate blood without becoming iron deficient. The ability of elderly women to become successful blood donors depends primarily on initial iron stores, iron intake, and frequency of donation. Women with low steady-state iron stores may be able to donate only two times per year without becoming iron deficient.


Axial and peripheral bone density and nutrient intakes of postmenopausal vegetarian and omnivorous women. The study investigated whether differences exist between postmenopausal Caucasian vegetarian and omnivorous women regarding trabecular and cortical bone density measured with single- and dual-photon absorptiometry. Anthropometric measurements, blood and urine samples, and food intakes of the twenty-eight matched pairs were also compared. The Wilcoxon signed-rank test indicated no significant differences in bone measurements between vegetarians and omnivores at any sites except the skull. The vegetarians' serum globulin and total protein measured higher. Urine calcium and creatinine were similar between the groups. The vegetarians consumed greater quantities of carbohydrate, fiber, magnesium, ascorbic acid, copper, and energy as percent carbohydrate, and lower quantities of protein, niacin, alcohol, vitamin B-12, cholesterol, and energy as percent protein. Despite several differences in dietary intakes, the results indicate that neither cortical nor trabecular bone density in these postmenopausal women was affected by a lactoovovegetarian diet.


Dietary patterns, eating behaviors, and bone mineral density in women runners. Although reduced gonadal steroid hormone concentrations appear to play a major role in lower trabecular bone mineral density (BMD) in women with athletic amenorrhea, dietary deficiencies and eating behaviors may also affect BMD in women runners. To investigate this possibility, dietary patterns (7-d records), eating-disorders inventory (EDI), and BMD were examined in nine nonrunning eumenorrheic control (Contl) and 32 women runners classified as eumenorrheic (n = 19, Eumen) and oligo/amenorrheic (a group in which some were oligomenorrheic and some were amenorrheic; Ol/Am, n = 13). Runner groups had similar cardiorespiratory fitness, body composition, and training characteristics. Lumbar spine BMD was lower in the Ol/Am runners (-12%, P less than 0.05) but proximal femur BMD did not differ. Dietary intake and EDI subscale scores were similar among the groups. However, there was an inverse trend between EDI subscale scores for bulimia and ineffectiveness and femoral BMD in the Ol/Am runners (r = -0.62 to -0.71, P less than 0.05). These results suggest that self-reported dietary intake and/or eating behaviors do not predict reproductive-function alterations in women runners, but eating behaviors may be associated with lower BMD in Ol/Am runners.


Blood glucose and insulin responses to different meals in non-insulin-dependent diabetic subjects of both sexes. The influence of sex on glucose and insulin responses in patients with non-insulin-dependent diabetes was studied in 12 men and 11 matched women. Two meals of either 100 g white bread or 60 g (raw weight) white rice were given. Blood glucose response areas to white bread (517 vs 509 mmol/L) and to rice (306 vs 353 mmol/L) over a 300-min observation period were similar in females and males, respectively. Insulin responses showed an identical pattern to that of glucose in females and males--35784 vs 28230 pmol/L after white bread and 28044 vs 19464 pmol/L min after rice (NS) over a 300-min observation period, respectively. Within the two study groups, blood glucose-response areas to white bread were significantly higher than those to rice (P less than 0.05), whereas there were no differences in insulin-response areas within or between the two groups. The glycemic index of rice for females (62 +/- 9; mean +/- SE) and males (66 +/- 5) was similar.


Value of Food and Agriculture Organization data on food-balance sheets as a data source for dietary fat intake in epidemiologic studies. The relationships between the per person supply (expressed as percent of total energy supply) of saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs) obtained from 1979-1981 Food and Agriculture Organization (FAO) data, and the per person intake obtained from 52 individual dietary surveys performed in 19 countries, were examined. In particular, the ratio of PUFAs to SFAs (P:S) and the ratio of unsaturated fatty acids (MUFAs and PUFAs) to SFAs (U:S) obtained from both data sources were examined. Significant correlations (P less than 0.001) were found between the two data sources for the P:S, U:S, SFAs, and MUFAs and PUFAs (P less than 0.02) in 19 countries. It is concluded that the data on fat intake from the FAO are valid for use in epidemiologic studies. In view of the variability of the data, it is recommended to use them either expressed as percentage of energy or as ratios of the different components.


Herman Award Lecture, 1992: lipid nutrition--a personal perspective. In the 1950s excess dietary fat was thought to be a risk factor for development of atherosclerosis. Over the ensuing years we have examined and given advice concerning first, saturation and unsaturation, and later, specific fatty acids such as oleic and stearic acids. Current work is further refining the delineation of fatty acids that might be harmful. Eventually, we will probably again cite excess fat as the problem.


McCollum Award Lecture, 1992: vitamin A absorption, transport, cellular uptake, and storage. We discuss vitamin A with emphasis on its absorption, transport, cellular uptake, storage, and intracellular metabolism. Dietary retinyl esters are hydrolyzed to retinol in the intestinal lumen before absorption by enterocytes. Carotenoids are absorbed and then partially converted to retinol in the enterocytes. In enterocytes retinol is esterified before incorporation into chylomicrons together with triacylglycerols. Chylomicrons reach the general circulation by way of the intestinal lymph, and chylomicron remnants are formed in the blood capillaries. The remnants, which contain almost all the absorbed retinol, are cleared by the liver parenchymal cells, and to some extent also by cells in blood, bone marrow, adipose tissue, and spleen. The uptake is most probably mediated via surface receptors for low-density lipoproteins or a low-density lipoprotein-receptor-related protein. In the liver parenchymal cells the retinyl esters are rapidly hydrolyzed to retinol, which binds to retinol-binding protein. Normally, most of the absorbed retinol coming into the liver parenchymal cell is transferred on retinol-binding protein to stellate cells, which store retinol as retinyl esters in lipid droplets.


Relationship of catecholamine excretion to body size, obesity, and nutrient intake in middle-aged and elderly men. Catecholamine release from sympathetic nerves and the adrenal medulla is influenced by diet under controlled research conditions. To test whether diet affects catecholamine excretion in free-living men, the urinary content of dopamine (DA), epinephrine (Epi), or norepinephrine (NE) was measured in 24-h collections provided by 572 participants of the Normative Aging Study of the Veterans Administration. Average daily intakes of energy and macronutrients were assessed by means of a semiquantitative food frequency questionnaire and sodium intake by quantitation of sodium excretion. Catecholamine excretion was also examined in relation to anthropometric variables. Because DA and Epi excretion were inversely related to age, all subsequent analyses included adjustments for age. Although DA and NE were positively related to measures of body size and fatness, Epi was negatively related to body fatness. Excretion rates of all three catecholamines were directly related to total energy intake and inversely related to energy-adjusted CHO consumption.


Is the impedance index (ht2/R) significant in predicting total body water? We investigated the general utility of bioelectrical impedance analysis (BIA) and the implications of BIA theory in populations of various ages from infancy to adulthood by developing a single impedance equation. Four subject data sets representing 62 adults, 37 prepubertal children, 44 preschool children, and 32 premature low-birth-weight neonates were combined. Subjects were randomly divided into a development group (n = 116) and a cross-validation group (n = 59). The single best predictor of total body water (TBW) was height2/resistance (ht2/R), which explained 99% of the variation in TBW (SEE = 1.67 kg). The addition of weight reduced the SEE to 1.41 kg. A significant bias was only seen in the preschool children. These results were confirmed in the cross-validation group and the best prediction formula was TBW = 0.59 ht2/R + 0.065 wt + 0.04. We conclude that the impedance index (ht2/R) is a significant predictor of TBW and that there is some improvement in prediction of TBW by inclusion of a weight term.


Lean-body-mass composition and resting energy expenditure before and after long-term overfeeding. This report deals with the association between the constituents of lean body mass (LBM) and resting metabolic rate (RMR) before and after a 100-d overfeeding period. Computed-tomography (CT) scan of 22 young adult males at nine different body levels were used to estimate adipose tissue mass (ATMCT), LBMCT, skeletal-muscle mass (SMMCT), and non-muscular LBMCT (NM-LBMCT). Before overfeeding, all body constituents, except ATMCT, were significantly correlated with RMR. Only body mass changes were significantly correlated with RMR changes. Comparison of these results with those of several studies in the literature reveals that the relationship between RMR and fat-free mass is highly influenced by the size of the SD for the latter variable. In stepwise-multiple-regression analysis, only SMMCT could be used to predict RMR. It was concluded that SMMCT and ATMCT, but not NM-LBMCT, increased during overfeeding and that the best correlates of RMR remain LBMCT, SMMCT, and body mass.


Prediction of resting energy expenditure from fat-free mass and fat mass. On the basis of literature values, the relationship between fat-free mass (FFM), fat mass (FM), and resting energy expenditure [REE (kJ/24 h)] was determined for 213 adults (86 males, 127 females). The objectives were to develop a mathematical model to predict REE based on body composition and to evaluate the contribution of FFM and FM to REE. The following regression equations were derived: 1) REE = 1265 + (93.3 x FFM) (r2 = 0.727, P < 0.001); 2) REE = 1114 + (90.4 x FFM) + (13.2 x FM) (R2 = 0.743, P < 0.001); and 3) REE = (108 x FFM) + (16.9 x FM) (R2 = 0.986, P < 0.001). FM explained only a small part of the variation remaining after FFM was accounted for. The models that include both FFM and FM are useful in examination of the changes in REE that occur with a change in both the FFM and FM. To account for more of the variability in REE, FFM will have to be divided into organ mass and skeletal muscle mass in future analyses.


Overfeeding and energy expenditure in humans. The effect of overfeeding on energy expenditure was investigated in 23 young men subjected to a 353-MJ energy intake surplus over 100 d. The major part of this excess (222 MJ) was stored as body energy. The increase in energy cost of weight maintenance amounted to 52 MJ and was proportional to body weight gain. When it was added to the obligatory cost of fat and fat-free mass gains, the overall increase in energy expenditure amounted to a mean of 100 MJ. Four months after overfeeding, subjects had lost 82%, 74%, and 100% of the overfeeding gain in body weight, fat mass, and fat-free mass, respectively. We conclude that 1) in response to overfeeding, two-thirds of the excess energy intake is stored as body energy; 2) overfeeding induces an increase in energy cost of weight maintenance proportional to body weight gain, and 3) preoverfeeding energy balance tends to be restored when nonobese individuals return to their normal daily-life habits.


Weight gain in adolescents during pregnancy: rate related to birth-weight outcome. This study of 459 subjects from prenatal clinics for teenagers at three universities across the United States, addresses questions about gestational weight gain in adolescents raised by the 1990 Institute of Medicine Report. Rate and pattern of gain, independent of pregravid weight, are based on serial measures of mothers with favorable and unfavorable outcomes. Rate of gain (determined by using regression statistics) from weeks 15 to 40 was 0.588, 0.510, and 0.488 kg/wk for mothers of term infants weighing 3000-4000 g, term infants weighing < 3000 g, and preterm infants, respectively. The significantly lower percentage of infants weighing 3000-4000 g vs < 3000 g needing intensive care at birth (6% vs 15%, respectively, P < 0.05) further indicates the superior outcome among mothers with higher rates of gain. Rate of gain of mothers of infants weighing 3000-4000 g (favorable outcome) equaled the highest amount provisionally recommended, suggesting that restricting natural gain of adolescents to recommended rates may result in smaller than optimal infants.


Energy intake, energy expenditure, and body composition of poor rural Philippine women throughout the first 6 mo of lactation. Between 6 and 30 wk postpartum, body weight and body-fat mass of 40 healthy, rural, lactating Filipino women decreased by 1.5 (P < 0.05) and 0.7 kg (P < 0.05), respectively. Energy intake decreased slightly (NS) from 8.84 +/- 2.05 MJ/d (2113 +/- 489 kcal/d; mean +/- SD) at 6 wk to 8.67 +/- 2.37 MJ/d (2073 +/- 566 kcal/d) at 30 wk. Basal metabolic rate (BMR) remained unchanged throughout lactation, and physical-activity level increased significantly (P < 0.05) from 1.61 +/- 0.17 x BMR at 6 wk to 1.97 +/- 0.18 x BMR at 30 wk. Energy intakes at 6 and 30 wk of lactation were 1.02 and 0.77 MJ/d (244 and 185 kcal/d) higher (P < 0.05), respectively, than in early pregnancy. At ages 1-6 mo, mean weights and lengths of mainly breast-fed infants had Z scores between 0 and -1. By using the growth patterns of the breast-fed infants as proxy indicators for adequacy of lactational performance, this study suggests that present recommended energy intakes for lactation are too high for healthy Filipino women who show adequate lactational performance.


Plasma lipids and lipoproteins during 6 d of maintenance feeding with long-chain, medium-chain, and mixed-chain triglycerides. This study assessed fasting plasma lipids and lipoproteins and postprandial plasma lipids in healthy male subjects fed liquid-formula diets containing 40% of total energy as long-chain (LCT, primarily C18:1 and C18:2), medium-chain (MCT, C8:0-C10:0), or mixed-chain (structured lipid, STL, mostly C8:0, C10:0, and C22:0) triglycerides for 6 d. None of the diets altered plasma cholesterol concentrations. HDL cholesterol was decreased 14% by the STL diet (P < 0.044) and 15% by the MCT diet (P < 0.004) but was unchanged by the LCT diet. Plasma triglycerides were elevated 42% by the MCT diet (P < 0.006), but were unaltered by either the STL or LCT diets. Neither the STL nor the MCT diets produced changes in fasting lipoprotein lipid composition; however, during the LCT diet, VLDLs became enriched in triglyceride and LDLs became enriched in cholesterol. Postprandial triglyceridemia was significantly greater after subjects consumed the LCT diet than it was after they consumed either the STL or MCT diets, which were similar. Short-term feeding of MCT and STL diets produces significant changes in lipid metabolism. An understanding of the long-term effects of these diets awaits further study.


Comparison of effects of lauric acid and palmitic acid on plasma lipids and lipoproteins. The effects of lauric acid (C12:0) on plasma lipids and lipoproteins were compared with the effects of palmitic acid (C16:0) and oleic acid (C18:1) in a metabolic-diet study of 14 men by using liquid-formula diets fed for 3 wk each in random order. Lauric acid was supplied in a synthetic high-lauric oil, palmitic acid was provided by palm oil and oleic acid in oleic-rich sunflower seed oil. The high-lauric oil resulted in higher concentrations of plasma total cholesterol (4.94 +/- 0.75 mmol/L [mean +/- SE]) and LDL cholesterol (3.70 +/- 0.57 mmol/L) when compared with high-oleic sunflower oil (4.44 +/- 0.54 and 3.31 +/- 0.44 mmol/L, respectively), but did not raise total and LDL cholesterol concentrations as much as did palm oil (5.17 +/- 0.65 and 3.93 +/- 0.51 mmol/L, respectively). No differences were noted in plasma triglycerides or HDL cholesterol. Lauric acid raises total and LDL cholesterol concentrations compared with oleic acid, but is not as potent for increasing cholesterol concentrations as is palmitic acid.


Leucine kinetics after a brief fast and in response to feeding in premature infants. To examine how feeding affects changes in leucine and protein metabolism, leucine kinetics were determined in nine preterm infants (32 +/- 2 wk gestation; mean +/- SD) after a brief fast and again during hourly feedings. Rates of leucine oxidation were similar during the fasting and feeding periods (31 +/- 4 vs 37 +/- 6 mumol.kg-1.h-1; mean +/- SE). The nonoxidative disposal rates of leucine (a reflection of protein synthesis) were also similar during both periods (228 +/- 20 vs 205 +/- 10 mumol.kg-1.h-1; mean +/- SE). In contrast, the rates of leucine release from endogenous protein (an indication of protein breakdown) were significantly reduced by feeding (259 +/- 23 vs 185 +/- 11 mumol.kg-1.h-1; mean +/- SE, P = 0.02). A significant positive correlation was demonstrated between the fasting rate of leucine release from endogenous protein and the degree of suppression produced by feeding (r2 = 0.796, P = 0.001). Conversely, a significant inverse correlation was shown between the nonoxidative disposal rate of leucine during fasting and the increase in response to feeding (r2 = 0.848, P < 0.001). These data suggest that premature infants respond to feeding after a brief fast by suppressing protein breakdown, rather than by increasing protein synthesis, and changes in protein metabolism produced by feeding in premature newborns may be influenced by the prevailing rates of protein breakdown and synthesis during fasting.


Vitamin B-6 depletion followed by repletion with animal- or plant-source diets and calcium and magnesium metabolism in young women. An 84-98-d study was conducted in young women to determine the effect of vitamin B-6-deficient diets on calcium and magnesium metabolism. A vitamin B-6-deficient formula diet fed initially was followed by either animal- or plant-source protein food diets containing four increasing amounts of vitamin B-6. Calcium balance was negative during vitamin B-6 depletion. Serum calcium was higher and calcium balance negative with the plant protein diets. Magnesium balance was negative during vitamin B-6 depletion due to increased urinary magnesium excretion. Urinary calcium decreased during vitamin B-6 depletion and increased as dietary vitamin B-6 increased. Urinary oxalate was significantly higher at the end than at the beginning of vitamin B-6 depletion and was higher with plant than animal protein diets. The results suggest that vitamin B-6 depletion may alter calcium and magnesium metabolism and that dietary components associated with the protein source may influence calcium retention.


Sex differences in postabsorptive plasma vitamin A transport. This study examined postabsorptive plasma vitamin A after doses of retinyl palmitate in healthy men (n = 28) and women (n = 31). On consecutive days one physiologic [3000 retinol equivalents (RE)] and one pharmacologic dose (105,000 RE) were administered and blood samples collected. Plasma retinol and retinyl esters were measured by HPLC. Tolerance curves were constructed by plotting plasma retinyl ester concentration vs time. Postprandial retinyl ester response was measured as peak rise in retinyl ester concentration and area under the curve (AUC). Peak plasma retinyl ester concentration occurred earlier for females but the earlier peak was significant only for younger subjects (< or = 50 y, P < 0.02) given the low dose and older subjects (> 50 y, P < 0.02) given the high dose. Peak rise and AUC were lower in females than in males, but this difference was significant for the high dose only (P < 0.05). In the high-dose experiment, when each age group was evaluated for sex differences the peak rise was significantly greater in males than in females in the older subjects (P < 0.05). Postabsorptive plasma retinol did not change from fasting concentrations. A lower plasma response in retinyl esters in women could be due to a more efficient chylomicron-remnant clearance.


Interactions among dietary manganese, heme iron, and nonheme iron in women. The relationship among dietary intake of heme iron, nonheme iron, and manganese on indexes of hematological and nutritional status in regard to manganese of 47 women consuming their typical diets was investigated. Increasing dietary iron intake, by consuming more nonheme iron in the diet, had questionable effects on hematological status (hematocrit values and ferritin and transferrin concentrations) and negative effects on nutritional status in regard to manganese (serum manganese, urine manganese, and lymphocyte manganese-dependent superoxide dismutase activity). In contrast, heme-iron intake was positively correlated with hematological status and had no consistent effect on nutritional status in regard to manganese. Differences in dietary manganese intake had no consistent effect on indices of manganese or iron status, possibly because foods that contain significant amounts of manganese (green vegetables, breads, and cereals) often contain significant amounts of nonheme iron. Thus, increasing dietary manganese intake by consuming these foods is apt to have limited impact on manganese status because of the interaction between nonheme iron and manganese.


Selenium status in patients with Crohn's disease. Twenty-seven of 66 patients with Crohn's disease had reduced concentrations of selenium and glutathione peroxidase in plasma and erythrocytes. When the patients were subgrouped according to the length of resected small bowel, a significant reduction of selenium and glutathione peroxidase in both plasma and erythrocytes was only found in patients with a resection > 200 cm. A highly significant correlation between selenium and glutathione peroxidase was found in plasma (r = 0.81) as well as in erythrocytes (r = 0.62), but no correlation was observed in the control group. A statistically significant correlation was also found between plasma selenium and the Harvey-Bradshaw score (r = -0.44), body mass index (wt/ht2) (r = 0.47), and plasma albumin (r = 0.29). Patients with a small-bowel resection > 200 cm appear to be at risk of developing severe selenium deficiency. These patients should have their selenium status monitored and probably receive selenium supplementation.


Diet, prolactin, and breast cancer.

Diet, prolactin, and breast cancer. Relationships between dietary nutrients and plasma prolactin concentration were studied in 249 women with a history of nonskin cancers among first-degree female relatives. For each quintile of nutrient density, the odds ratio (OR), relative to the lowest quintile, of having an elevated (above the median) prolactin concentration was estimated by logistic regression, taking into account parity, menopausal status, and current tobacco-smoking habits. For nutrient densities estimated from 24-h recall data there was a significant positive association between plasma prolactin concentration and increasing saturated fatty acid intake; the OR of elevated prolactin in the top quintile was 3.1 [95% confidence interval (CI) 1.2-8.1] and there was a negative association with vitamin C [OR in the top quintile 0.28, (95% CI 0.10-0.78)]. For usual nutrient densities (estimated by quantitative food frequency questionnaire) there was a statistically significant trend (P = 0.04) toward lower prolactin concentrations with increasing sodium density, and a marginally significant positive trend (P = 0.07) with increasing dietary density of refined sugars.


Histologic changes in liver biopsy specimens produced by recombinant interferon alpha-2b therapy for chronic non-A,non-B viral hepatitis. A randomized controlled trial. The effects of interferon therapy on liver histologic findings were assessed in a randomized controlled trial consisting of 80 patients with chronic non-A,non-B hepatitis. Twenty-eight patients received 1 million units of recombinant interferon alpha-2b; 25 patients received 3 million units, subcutaneously, three times a week for 24 weeks; and 21 patients were observed as untreated controls; all of them underwent liver biopsy within 6 months from the beginning of the study and on the last day of therapy. Six patients were withdrawn from the study because of inadequate liver biopsy specimens. Alanine aminotransferase levels were determined before, during, and after therapy. For each biopsy, a semiquantitative score of histologic features, the histologic activity index, and the overall histologic assessment were performed. Ninety-five percent of patients tested positive for hepatitis C virus antibody. Portal inflammation, piecemeal and spotty necrosis, and bile duct proliferation were significantly decreased in patients with normalized alanine aminotransferase. The effectiveness of therapy was dose dependent: piecemeal and spotty necrosis and the histologic activity index showed a significant decrease only in 3-million-unit-treated patients. Hepatocellular degeneration and fibrosis did not change significantly after treatment.


Histologic changes in Chinese patients with chronic hepatitis B virus infection after interferon-alpha therapy. To evaluate the histologic effects of interferon-alpha (IFN alpha) therapy on chronic hepatitis B virus (HBV) infection, a semiquantitative study using a modified Knodell's numeric histologic scoring system was performed on paired pre- and post-treatment liver biopsy specimens from 127 adult Chinese patients from two trials of IFN alpha therapy (IFN alpha, n = 86; control, n = 41). The effects of IFN alpha therapy on the hepatic expression of HBV antigens were also determined using immunohistochemical analysis. Serologic response with clearance of HBV e antigen (n = 18) was associated with reduction in lobular activity, periportal piecemeal necrosis, portal inflammation, and total histologic scores. Loss of HBV e antigen also was associated with a reduction in the amount of HBV core antigen in the hepatocytes. In contrast, there was an increase in hepatic expression of HBV surface antigen after IFN alpha therapy. Patients who lost HBV e antigen with IFN alpha therapy were characterized by more severe initial periportal piecemeal necrosis before treatment. These data indicate that (1) serologic response is associated with a reduction in hepatic HBV replication and an improvement in hepatic histology, and (2) patients with severe periportal piecemeal necrosis respond more favorably to IFN alpha therapy.


The use of monoclonal antibodies against primary myeloid granules in normal and leukemic cells. Three monoclonal antibodies, K101, D46, and H36/71 (CD15), reactive with membrane components of primary granules of human promyelocytes, were studied to assess their binding to normal and leukemic cells. Using the alkaline phosphatase antialkaline phosphatase technique, these antibodies were applied to sections of normal organs and to peripheral blood and bone marrow films from hematologically normal individuals and patients with hematologic malignancies. In control experiments, antibodies showed reactivity with cytoplasmic constituents of granulocytes from the promyelocytic to the neutrophilic stage. In acute myeloid leukemia, antibody K101 was positive (more than 20% of blasts) in 13 of 21 (62%) cases, while antibody D46 was positive in 11 of 17 (65%) cases. Antibody H36/71 was positive in only 4 of 24 (17%) cases of acute myeloid leukemia. At least one marker was present in 6 of 8 (75%) cases of acute lymphoblastic leukemia with myeloid antigen-positive blasts and was negative in 20 cases of acute lymphoblastic leukemia with myeloid antigen-negative blasts. These results support the view that abnormal granules (with defective expression of the D46, K101, and H36/71 antigens) form in blastic and leukemic cells of patients with acute myeloid leukemia. Data also suggest that membrane components of myeloid granules are made in the cytoplasm of cells from some acute lymphoblastic leukemia patients with myeloid antigen-positive blasts.


Clinical significance of immunoglobulin A versus immunoglobulins G and M anti-cardiolipin antibodies in patients with systemic lupus erythematosus. Correlation with thrombosis, thrombocytopenia, and recurrent abortion. Serum levels of immunoglobulins (Ig) A, G, and M anti-cardiolipin (aCL) antibodies were determined by enzyme-linked immunosorbent assay in a group of selected systemic lupus erythematosus female patients. Patients were divided into three groups based on their clinical history of thrombosis with or without thrombocytopenia (group I), thrombocytopenia alone (group II), and neither of these (group III). After the aCL antibody levels were determined, the patients' obstetric histories of pregnancies and abortions were reviewed. A high incidence of one or more abortions was seen only in group I patients. A high prevalence of elevated levels of IgA and IgG (but not IgM) aCL antibodies was observed in group I patients. However, among the patients in group II, only the levels of IgA aCL antibodies were increased. In both groups, the addition of the IgA aCL determination--to the classical IgG and IgM aCL assays--increased the prevalence of positive reactors in 31.6%. These results indicate that high levels of IgA aCL antibodies correlated better with thrombocytopenia than either IgG or IgM. Also, the importance of including the determination of IgA aCL antibodies to assess properly the risk of thrombosis, thrombocytopenia, and recurrent abortions in systemic lupus erythematosus patients is demonstrated.


Risk factors for drug use in urban adolescents: identification and cross-validation. Examined the relationship between 26 dichotomous risk factors and drug use in derivation (N = 1,352) and cross-validation (N = 1,309) samples of seventh graders in the public school system of a large southeastern city. The majority of students was African American, many came from low-income, single parent families. A total of 20 risk factors representing a variety of variables was significantly related to at least one category of drug use in both samples. Regression analyses identified a subset of 11 risk factors with minimum overlap. The simple sum of these 11 risk factors was significantly associated with prevalence of use for cigarettes, beer and wine, hard liquor, marijuana, and other drugs. The total number of risk factors also showed a curvilinear relationship with the frequency of 30-day use for each category of drug. Theoretical and practical implications of these findings are discussed.


An advocacy intervention program for women with abusive partners: initial evaluation. Experimentally tested the hypotheses that (1) battered women are in need of numerous community resources upon exit from a domestic violence shelter, (2) working with advocates increases women's effectiveness in obtaining needed resources and social support, and (3) success in obtaining resources and social support increases women's levels of life satisfaction and decreases their risk of further abuse. The initial findings of a short-term intervention project designed to provide postshelter advocacy services to women with abusive partners are presented. One-hundred forty-one battered women were interviewed immediately upon their exit from a domestic violence shelter as well as 10 weeks thereafter. Half the sample was randomly assigned to receive the services of trained advocates who assisted them in accessing needed community resources. Women who worked with advocates reported being more effective in accessing resources and had higher levels of social support and overall quality of life postintervention. Although all women reported some decrease in postshelter abuse, there were no differences between those with and those without advocates, and abuse continued to be a problem for many women.


The relation of peer social support and psychological symptomatology during the transition to junior high school: a two-year longitudinal analysis. Studied the longitudinal relation of peer social support and psychological symptomatology among a sample of 143 early adolescents during a two-year period spanning the transition from elementary school to junior high school. Correlational analyses indicated strong inverse relations between peer support and symptoms, both cross sectionally and across time. Prospective analyses investigated the degree to which prior levels of peer support were related to subsequent symptoms after controlling for initial levels of symptoms and, conversely, the degree to which prior symptoms were related to future levels of peer support after controlling for initial levels of support. A significant prospective effect for peer support was found only for the specific period encompassing the school change. Prospective effects for symptoms were more numerous and of longer duration. The discussion emphasizes how the relation among support, stress, and mental health may differ over the course of a major life transition. Implications are also considered for the timing of preventive interventions.


The role of life events, family support, and competence in adolescent substance use: a test of vulnerability and protective factors. Tested propositions from a model of vulnerability and protective factors with a multiethnic sample of 1,289 urban adolescents, aged 11-13 years. The criterion variable was a composite score for cigarette, alcohol, and marijuana use. Multiple regression analyses indicated that vulnerability factors (negative life events, negative affect) were related to a higher level of substance use, and protective factors (parent emotional and instrumental support, academic and adult competence, positive affect) were related to a lower level of substance use; peer competence was positively related to substance use in a multivariate model. There was a significant overall interaction of Vulnerability x Protective Factors, consistent with a stress-buffering effect. Individual interactions for Life Events x Family Support, Life Events x Competence, and Negative x Positive Affect also were consistent with buffering effects. Implications for theories of substance use and primary prevention are discussed.


Social support in chumships and adjustment in children of divorce. Examined the relations between support from intimate friends or "chums" and stress, age, and gender in predicting psychological adjustment using a sample of 117 8- to 15-year old children who had experienced parental divorce. Both parents and children provided information on children's adjustment. In predicting children's reports of their adjustment, the direct effect of chum support was found to be moderated by children's age. In predicting parental reports of children's adjustment, no significant main effects or interaction effects occurred. The findings are discussed with attention to the divergent perspectives of different reporters.


Immunogenicity and reactogenicity of Takeda acellular pertussis-component diphtheria-tetanus-pertussis vaccine in 2- and 3-month-old children in Japan. To compare the reactogenicity and immune response to the Takeda acellular pertussis-component diphtheria-tetanus-pertussis (APDT) vaccine in children when immunization commenced at 2 months (group A) vs 3 months (group B) of age. Longitudinal, nonblinded, comparative study. Pediatric well-child clinics. Healthy 50- to 98-day-old infants. Good antibody responses to lymphocytosis-promoting factor, filamentous hemagglutinin, agglutinogens, and pertactin occurred in both age groups after both the third and fourth vaccine doses. Both young age and transplacentally acquired maternal antibody independently and together have a suppressive effect on the response to the four antigens in this APDT vaccine. However, these effects appear to be minor. Vaccine reactions were mild; group A children had slightly but not significantly higher rates than group B children. The present US diphtheria and tetanus toxoids and pertussis vaccine immunization schedule should also be satisfactory with this acellular pertussis component vaccine.


The agglutinin response to whole-cell and acellular pertussis vaccines is Bordetella pertussis--strain dependent. To determine the significance of the Bordetella pertussis strain used as the antigen in the agglutinin assay for the evaluation of pertussis vaccines. Randomized, double-blind study. Health maintenance organization clinics, primary care clinic at a referral hospital, and private practices in Los Angeles County, California. Forty healthy infants. Convenience sample. Twenty infants received whole-cell pertussis-component diphtheria-tetanus-pertussis vaccine (DTP), and 70 infants received acellular pertussis-component diphtheria-tetanus-pertussis vaccine (APDT) at ages 2, 4, and 6 months. The agglutinin assay was performed using three separate B pertussis strain preparations: (1) strains 130 and 138 in equal quantities, the constituents of the DTP vaccine, (2) strain 460, and (3) strain Tohama, the constituent of the APDT vaccine. The agglutinin titers were highly strain dependent; in both groups of vaccinees at both ages the Tohama values were highest, followed by strain 460 and then strains 130/138. The vaccine groups had comparable titers at age 2 months regardless of the assay antigen used. However, at age 7 months, after three immunizations, the DTP group geometric mean titer was more than 10 times greater than that of the ADPT group using strains 130/138, but only 2.6 times higher using strain 460 and almost equivalent using Tohama strain. Vaccine group agglutinin value comparisons strongly depend on assay antigens used.


Confirmation. Practice behavior for treatment of new morbidity disorders reflects residency experience. The purpose of the present study was to evaluate congruence between practice and residency training in the treatment of children with five "new morbidity" disorders. Data were obtained through mailed questionnaires. Counseling and behavior modification, without medications, were used for all five disorders by respondents most recently completing pediatric residency. Medications were used more frequently by pediatricians who had completed their residency training longer ago, particularly for nocturnal enuresis and chronic abdominal pain. The most recent graduates tended to treat a larger number of children with temper tantrums and separation anxiety. This is believed to result from more recent graduates being more comfortable and confident in recognizing and treating these conditions. In contrast, no association was noted between year in which residency was completed and number of children treated for nocturnal enuresis and chronic abdominal pain. This results from parents volunteering these symptomatic conditions since they perceive them to be medical problems.


Uses and technique of pediatric lumbar puncture. To review diagnostic and therapeutic indications, contraindications, complications, and technique of pediatric lumbar puncture with emphasis on diagnosis of bacterial meningitis in bacteremia, cellulitis, and fever with seizures and to discuss cerebrospinal fluid findings in partially treated infection and traumatic blood-contaminated spinal tap. Literature review. We recommend lumbar puncture for children younger than 1 year with bacteremia, children with Haemophilus influenzae type B cellulitis, and children with fever and seizures not classified as simple. Pretreatment with antibiotics rarely changes cerebrospinal fluid characteristics such that a diagnosis of bacterial meningitis would be obscured. In a traumatic spinal tap, the equation to predict cerebrospinal fluid pleocytosis based on the peripheral blood cell count is invalid. When used together, cerebrospinal fluid glucose level, Gram's staining, and observed-to-expected ratio of white blood cells are highly reliable in diagnosing bacterial meningitis.


Pediatric tuberculosis and human immunodeficiency virus infection in Palm Beach County, Florida. To describe the factors underlying an increasing incidence of tuberculosis in children. Descriptive case review. Palm Beach County, Fla. Forty-four children with suspected and confirmed pediatric tuberculosis from 1985 through 1989. None. From 1988 through 1989, tuberculosis was confirmed in 15 children and suspected in another 16 compared with data from 1985 through 1987 in which the disease was confirmed in nine children and suspected in four. Pediatric tuberculosis occurred primarily in blacks younger than 5 years; the increase in the number of cases reported in 1988 and 1989 occurred only in blacks. One child in whom tuberculosis was confirmed during the recent period was infected with the human immunodeficiency virus (HIV); however, among children with suspected tuberculosis, four of the nine children tested were seropositive for HIV. There was no evidence of increased transmission of tuberculosis to children by HIV-seropositive adults compared with transmission by HIV-seronegative adults with TB. New adult tuberculosis cases in the county increased annually, from 92 cases in 1986 to 169 in 1989, of whom at least 36% were infected with HIV. The largest effect of the HIV epidemic on tuberculosis in children appeared to be indirect, through an increase in the number of adults with active tuberculosis serving as potential sources of tuberculosis infection for children. A direct effect of HIV infection in the progression of tuberculous disease in children is likely, but was not detected in this investigation. Case-finding for tuberculosis among children will need to increase, particularly in areas heavily affected by acquired immunodeficiency syndrome, but may be complicated by the difficulty of diagnosing tuberculosis in HIV-infected children.