Preservation of normal adrenal androgen secretion in end stage renal disease

A common endocrine defect in uremia is gonadal dysfunction with decreased testosterone production. Since gonadal and adrenal tissues share androgen biosynthetic pathways, we studied the stimulated adrenal androgen response in uremic patients. In contrast to the delayed or subnormal gonadal response to hCG reported by others, the adrenal response of androgens, as well as cortisol and aldosterone, to cosyntropin stimulation was unimpaired. In summary, the secretory reserve capacity of the adrenal gland for androgen, glucocorticoids and mineralocorticoids in uremia was studied with cosyntropin stimulation and found to be wall preserved.     

A genetic component to the variation of dehydroepiandrosterone sulfate

Previous studies have shown wide variation in the normal range of serum concentrations of adrenal androgens, including dehydroepiandrosterone (DHA), and DHA sulfate (DHAS). Much of this variability has been shown to be due to the marked variation of the concentrations of these hormones with age. In a search for other sources of this variation, we examined the distribution of DHAS levels in 178 individuals drawn from 26 families. DHAS was chosen because of its relatively high serum concentration, long half-life, and lack of pulsatile variation. As expected, we observed a large age effect, such that it accounted for 68% of the overall variability. In addition, however, when age was factored out by appropriate polynomial regression, there was a significant genetic component to the residual variation, with a heritability of 65%. Thus there appeared to be a significant genetic determination to DHAS serum levels. The results are in accord with previous studies suggesting a genetic component to the variation in testosterone and sex hormone globulin concentrations, and the known correlation of DHAS and testosterone levels. Thus there appears to be significant genetic control of androgen concentrations in humans.     

Clinical experience with rate-controlled delivery of antihypertensive therapy by a transdermal system

The efficacy of transdermal clonidine, alone and in combination with diuretics, has been demonstrated in several studies involving patients with mild to moderate essential hypertension. In one 3-month open study, 64% of patients (wearing one to three 3.5 cm2 transdermal patches) achieved sustained blood pressure reductions throughout the treatment period. In this large study, side effects requiring discontinuation of drug were not observed. Transdermal clonidine reduced plasma renin activity and urinary aldosterone excretion to the same extent as that reported for oral clonidine. Renal function or serum electrolytes were not affected during therapy with transdermal clonidine. Another study showed that patients receiving oral clonidine and hydrochlorothiazide experienced comparable blood pressure reductions when switched to transdermal patches. Plasma drug concentrations measured during treatment with the transdermal patches were similar to the trough levels observed during treatment with oral clonidine. The equipotency of oral and transdermal therapy in combination with hydrochlorothiazide was also demonstrated in two remaining studies. In one of these studies it was suggested that daily variations in blood pressure induced by the peak and trough drug levels of the oral form were minimized by the stable drug levels characteristics of the transdermal device.     

Incidence of mitral valve prolapse in one hundred clinically stable newborn baby girls: an echocardiographic study.

Clinical and echocardiographic examinations were performed on 100 clinically stable, newborn baby girls. Mitral valve prolapse was noted on the echocardiograms of seven babies. Three subjects had systolic clicks, two of whom had systolic murmurs following the click. The four other babies who had echocardiographic evidence of mitral valve prolapse had no abnormal auscultatory signs. Of the 93 babies without evidence of mitral prolapse, 91 had normal echocardiograms and auscultatory features; one was noted to have a murmur consistent with a ventricular septal defect, and another had an eccentric aortic valve on the echocardiogram which was suggestive of a bicuspid aortic valve. Serial studies on our group of subjects will yield useful information regarding the natural history of mitral valve prolapse.     

Single-agent and combination therapy of essential hypertension

Patients with mild to moderate essential hypertension were treated with beta-blockers and diuretics given separately and in combination. During single-drug therapy, the majority of patients exhibited clearly superior antihypertensive responses to either one type of drug or the other; only rarely were the beta-blockers and the diuretic equally effective in an individual patient. A poor response to diuretic therapy tended to predict a good response to a beta-blocker, and vice versa. Pretreatment renin measurements were not helpful in predicting the differing responses to single-drug treatment in this study population. These findings indicate that when one of these types of drug is ineffective as monotherapy in treating hypertension, the other type should be substituted before considering combination treatment. Combined therapy with the beta-blockers and diuretics also gave variable results, although poor antihypertensive responses could be attributed to excessive stimulation of the renin-aldosterone system by the diuretic component of the combination. The effectiveness of this form of treatment might thus be enhanced by the use of low diuretic doses.     

Effects of rapid digitalization on total and regional myocardial performance in patients with coronary artery disease

In order to evaluate the effects of rapid digitalization on LV volumes, ejection fraction, and asynergy, 21 patients without heart failure were studied with a combination of hemodynamic and angiographic techniques before and after administration of intravenous ouabain (0.007 mg./Kg.). Seven patients had no CAD and served as normal (control) subjects (Group I), while 14 patients had extensive coronary disease (Group II). All pre-ouabain parameters were within the normal limits in Group I. After ouabain infusion, all indices of LV contractility: $\text{dP}\text{dt}$, V_CF, and ejection fraction rose significantly in the normal group, while LV filling pressure and end-diastolic volume remained unchanged.The baseline hemodynamic and volumetric values for Group II patients corresponded closely to their normal (Group I) counterparts, and exhibited similar changes after ouabain administration. Eight patients in Group II also had regional disorders of LV contractility, delineated by 23 abnormal hemiaxes of shortening. After ouabain, 15 out of 23 asynergic segments (65 per cent) improved, seven remained unchanged, and one worsened. It is therefore concluded that rapid digitalization not only enhances LV performance in normal subjects and in patients with CAD, but can also markedly reduce the extent of LV asynergy.     

Left main coronary arterial patency assessed with cross-sectional echocardiography

To assess the ability to visualize the left main coronary artery with cross-sectional echocardiography, 123 patients scheduled to undergo coronary arteriography were studied prospectively. The left main coronary artery was visualized with a phased array sector scanner. Coronary arteriography revealed a normal left main coronary artery in 108 of the 123 patients and more than 50 percent stenosis of this vessel in 15 patients. The left main coronary artery was adequately visualized with crosssectional echocardiography in 62 (57 percent) of the 108 patients with an arteriographically normal artery and in 9 (80 percent) of 15 patients with more than 50 percent stenosis of this vessel. Cross-sectional echocardiography indicated a normal left main coronary artery In 59 of the 108 patients with a normal left main vessel on coronary arteriography. In three patients thought to have greater than 50 percent stenosis of the distal left main coronary artery on cross-sectional echocardiography, coronary arteriography revealed significant stenosis of the proximal left anterior descending coronary artery and a normal left main coronary artery. In all nine patients with more than 50 percent stenosis of the left main coronary artery on coronary arteriography and adequate visualization of this vessel on cross-sectional echocardiography, the latter technique revealed narrowing of the lumen of this vessel. It is concluded that: (1) When the left main coronary artery is adequately visualized with crosssectional echocardiography, the presence or absence of more than 50 percent stenosis of this vessel can be assessed. (2) Stenosis of the proximal left anterior descending coronary artery may mimic a distal left main coronary arterial stenosis. (3) Studies on larger numbers of subjects with left main coronary artery disease will help to delineate further the role of cross-sectional echocardiography in evaluating a patient with suspected disease of this artery.     

Innominate artery aneurysm with thrombus: detection by two-dimensional echocardiography

A 51 year old man with an innominate artery aneurysm presented with claudication and ischemia of the right forearm and hand. Two-dimensional echocardiography visualized the saccular aneurysm and a pedunculated mobile thrombus within it that were not seen during aortic arch angiography. Two-dimensional echocardiography, shown to be useful in identifying intracardiac masses and aortic aneurysms, may be important in selecting patients with increased risk of embolization.     

The circadian blood pressure pattern in ambulatory normal subjects

Ambulatory blood pressure (BP) monitoring using a portable noninvasive device capable of automatically measuring and recording BP every 7.5 minutes during a 24-hour study period was performed in 34 normal volunteers on 2 separate occasions, 2 to 8 weeks apart, to test the consistency of the whole-day blood pressure pattern. The average of all systolic BPs measured during the second study day was within 10 mm Hg of that measured during the first study day in 79% of the subjects, and the respective diastolic BP averages were within 5 mm Hg of each other in 65 % of the subjects; 53 % satisfied both of these criteria. The reproducibility of the circadian pattern of the BP was tested by dividing the 24-hour day into 12 consecutive 2-hour BP averages. When the corresponding 2-hour periods on the 2 study days were matched, there were strong correlations (r > 0.70) within most subjects for both the systolic and diastolic BP averages of the 2-hour periods (76% and 68% of subjects) and for the relative rank values of the periods (62% and 56%). Moreover, there were no significant differences between the averages (for all subjects together) on the 2 study days of the highest and lowest systolic and diastolic 2-hour BP values; similarly, the times at which these extreme values occurred on the 2 study days corresponded closely. Thus, in normal subjects there is a strong tendency for the circadian pattern and the actual levels of BP to be consistent between 24-hour study periods.     

Spatial R wave amplitude changes during exercise: relation with left ventricular ischemia and function

Thirty patients who exhibited increased and 65 patients decreased spatial R wave amplitude during exercise testing were compared for left ventricular function and ischemic variables. Spatial R wave amplitude was derived from the three-dimensional Frank X, Y, Z leads using computerized methods. All patients had stable coronary artery disease and they were classified into two groups: one that attained a higher (n = 48) and one a lower (n = 47) median value of maximal heart rate during exercise (161 beats/min). Within these two groups, patients with increasing or decreasing spatial R wave amplitude during exercise were analyzed for differences in oxygen consumption, exercise-induced changes in spatial R wave amplitude, ST segment depression laterally (ST60, lead X), ST displacement spatially, left ventricular ejection fraction at rest, change in left ventricular ejection fraction with exercise and thallium-201 ischemia during exercise. Significant differences were demonstrated only in exercise-induced spatial R wave amplitude changes (p less than 0.0001). There was no significant correlation between exercise-induced change in heart rate and change in spatial R wave amplitude in either the group with increasing or the group with decreasing spatial R wave amplitude. It is concluded that changes in spatial R wave amplitude during exercise are not related to ischemic electrocardiographic or thallium-201 imaging changes or to left ventricular ejection fraction determined at rest or during exercise.     

Antianginal and myocardial metabolic properties of verapamil in coronary artery disease

To determine the metabolic cost of administering an experimental calcium antagonist, verapamil, to patients with coronary artery disease, 12 such patients were studied at rest and during stress with atrial pacing before and after intravenous treatment with verapamil (bolus dose of 0.1 mg/kg body weight, followed by infusion at 0.005 mg/kg per min). The mean (±standard deviation) aortic pressure at rest (98 ± 22 mg Hg), coronary sinus blood flow (88 ± 17 ml/min) and myocardial oxygen consumption (10.7 ± 2.4 ml O₂/min) decreased to 88 ± 20 mm Hg (p < 0.0004), 77 ± 14 ml/min (p < 0.03) and 8.8 ± 2.5 ml O₂/min (p < 0.01), respectively, after administration of verapamil. With atrial pacing, these values were 105 ± 25 mm Hg, 151 ± 50 ml/min and 18.5 ± 6.4 ml O₂/min, respectively, before infusion of verapamil, and then decreased to 87 ± 14 mm Hg (p < 0.006), 107 ± 31 ml/min (p < 0.0002) and 13.3 ± 4.4 ml O₂/min (p < 0.001) during infusion. Angina occurred in all patients with atrial pacing before verapamil (threshold to pain: 93 ± 67 seconds). After verapamil, the threshold to pain in six patients increased to 191 ± 183 seconds; and no pain was experienced by the remaining six (p < 0.0005). Before administration of verapamil lactate extraction decreased from 24 ± 9 to 10 ± 11 percent (p < 0.0002) during atrial pacing, and 9 (75 percent) of the 12 patients exhibited electrocardiographic S-T segment depressions. After administration of verapamil lactate extraction normalized to 22 ± 9 percent during atrial pacing, and the electrocardiogram reverted to baseline in all but one patient. These findings indicate that verapamil decreases left ventricular myocardial metabolic demands, and concomitantly greatly increases the threshold to angina.     

Myocardial metabolism and threshold to angina in coronary artery disease after digitalization: responses at rest and during stress.

To determine the metabolic cost of digitalis to patients with coronary artery disease who were not in congestive heart failure, 15 patients were stressed with atrial pacing before and after the administration of ouabain (0.007 mg/kg). Resting coronary sinus blood flow (118 ± 31 ml/min) and myocardial oxygen consumption (15.8 ± 3.5 ml oxygen/min) increased to 141 ± 25 ml/min (P < 0.05) and 19.8 ± 3.8 ml oxygen/min (P < 0.02) after ouabain administration, but there was no shift to lactate production and no angina. Atrial pacing before and after the infusion of ouabain induced a shift to lactate production (before ouabain: +29 per cent to -3 per cent, P < 0.05; after ouabain: +36 per cent to ?2 per cent, P < 0.01), caused angina in 12 patients (80 per cent) and S-T segment depression in nine patients (60 per cent) whether ouabain was given or not. Furthermore, atrial pacing alone versus atrial pacing plus ouabain produced no significant differences in coronary sinus blood flow (178 ± 63 to 181 ± 90 ml/min) and myocardial oxygen consumption (22.8 ± 6.6 to 23.5 ± 10.1 ml oxygen/min). Yet, 11 of 12 patients (92 per cent) experienced angina within a much shorter period of time after the institution of atrial pacing (152 ± 119 seconds to 46 ± 41 seconds, P < 0.01) if they had previously received ouabain.These findings indicate that digitalization increases myocardial oxygen consumption in nonfailing hearts with coronary artery disease but that this increase is not accompanied by a shift to anaerobic metabolism at rest. Although prior digitalization does not appear to produce additional deleterious metabolic effects during stress, it may sensitize patients to a much earlier awareness of angina.     

Echographic early systolic partial closure (notching) of the aortic valve in congestive cardiomyopathy

We investigated the prevalence and significance of aortic valve early systolic partial closure (notching) in congestive cardiomyopathy by reviewing clinical and M-mode echocardiographic findings in 33 patients. We also compared their echocardiographic aortic root and valve findings to those in 17 aortic regurgitation patients and 24 normal subjects. Thirteen cardiomyopathy patients (39%) exhibited aortic valve partial closure--similar to the prevalence in the aortic regurgitation (41%) and normal (33%) groups. However, patients with dilated cardiomyopathy and aortic valve notching exhibited a higher mean percentage of partial closure (18% +/- 10) than those with notching in either the aortic regurgitation (8% +/- 9) or normal (5% +/- 2) group. There was no significant difference in age, body surface area, left ventricular dimension, systolic function, or presence of mitral regurgitation between cardiomyopathy patients with and without aortic valve notching, but the former had slightly greater aortic root dimensions and maximal aortic leaflet separation. Although the reason for this difference is unknown, a wider aortic root may result in low-pressure areas bordering the aortic flow stream during early systole, which may favor partial aortic valve closure.     

Circadian blood pressure patterns in ambulatory hypertensive patients: Effects of age

Circadian blood pressure monitoring was performed in 50 untreated ambulatory hypertensive patients to study the effects of age on the pattern and variability of Mood pressure and heart rate. Casual blood pressure, measured in the morning, was greater than the average of the blood pressures measured at 7.5 minute intervals for 24 hours (148 ± 2/95 ± 2 and 137 ± 2/88 ± 2 mm Hg, p < 0.001). The correlation between casual systolic pressure and the 24 hour average was stronger (p < 0.05) in younger (less than 55 years of age) patients (r = 0.69, n = 24, p < 0.001) than in older patients (r = 0.42, n = 26, p < 0.1). Similarly, diastolic pressures correlated more strongly (p < 0.05) in younger patients (r = 0.71, p < 0.001) than in older patients (r = 0.43, p < 0.05). Variability of systolic pressure, defined as the standard deviation of all readings obtained during 24 hours, was greater than that of diastolic pressure (16.7 and 13.1 mm Hg, respectively, p < 0.001). Moreover, the variability of systolic pressure was greater in older than in younger patients (18.1 and 15.2 mm Hg, respectively, p < 0.01). The variability of diastolic pressure was slightly but not significantly greater in older patients (13.7 and 12.5 mm Hg, not significant). The Circadian pattern of blood pressure, expressed as averages of readings obtained during consecutive 2 hour intervals, was similar in the two age groups. However, the level of systolic pressure was consistently higher (p < 0.01) and that of both diastolic pressure and heart rate consistently tower (p < 0.01) in older patients. Thus, ambulatory circadian blood pressure monitoring reveals significant changes in blood pressure levels and its variability with age; the casual blood pressure does not accurately reflect these changes. Longer periods of Mood pressure monitoring are required for accurate assessment of the characteristics of hypertension in the aged.