Arterial hemodynamics in human hypertension.

Differences in aortic impedance between normotensives and hypertensives are not well characterized. We examined impedance in 8 normotensive and 11 hypertensive (mean 96.7 vs. 122.2 mmHg) age-matched, Chinese patients undergoing cardiac catheterization at rest, during nitroprusside, and handgrip exercise before and after beta blockade (propranolol). Hypertensives had higher resistance (2,295 vs. 1713 dyn-s/cm5), characteristic impedance (145.7 vs. 93.9 dyn-s/cm5), total external power (1,579 vs. 1174 mW), peripheral reflections (ratio of backward to forward wave components of 0.54 vs. 0.44), and first zero crossing of impedance phase angle (4.15 vs. 2.97 Hz). These abnormalities were eliminated with vasodilatation. Differences between groups were not further exacerbated when pressure was increased during handgrip exercise. Beta blockade further increased resistance and reflections. Thus, hemodynamic abnormalities of essential hypertension (increased resistance, reflections, and pulse wave velocity, and decreased compliance) are compatible with an increased vasomotor tone that is further unmasked during generalized beta blockade.

Mechanisms of verapamil-induced conduction block in anomalous atrioventricular bypass tracts.

Verapamil, a calcium channel blocking agent, has been demonstrated to have depressive effects on the atrioventricular (AV) node but not anomalous AV bypass tracts. Of 39 patients with AV reciprocating tachycardia utilizing left-sided bypass tracts for retrograde conduction, intravenous infusion of verapamil (0.15 mg/kg) terminated the tachycardia in 31 patients. Verapamil interrupted the tachycardia circuit by inducing retrograde conduction block in the bypass tract rather than the AV node in 5 of these 31 patients. Electrophysiologic studies in these five patients revealed that verapamil-induced conduction block in the bypass tract could be accounted for by two distinctly different mechanisms. In three patients, verapamil induced alternating slow and fast AV nodal conduction resulting in alternating long and short cycle lengths during the tachycardia; consequently, development of the Ashman phenomenon in the bypass tract terminated the tachycardia. In the remaining two patients, the bypass tract exhibited properties similar to those of the AV node; verapamil prolonged the effective refractory period of the bypass tract, thereby terminating the tachycardia. Thus, depending on the functional properties of the bypass tract, verapamil may interrupt an AV reciprocating tachycardia circuit by exerting either a direct or indirect depressive action on the bypass tract.

Echocardiographic study of cardiac abnormalities in families of patients with Marfan's syndrome.

Twelve patients (5 male and 7 female; mean age 17.7 +/- 12.3 years, range 5 to 42) with Marfan's syndrome and 48 of their first degree relatives (16 male and 22 female; mean age 29.8 +/- 17.3 years, range 4 to 60) were evaluated for cardiac abnormalities by echocardiography. Of the patients with Marfan's syndrome, aortic valve prolapse was present in 1, tricuspid valve prolapse in 4, mitral valve prolapse in 12 and aortic root dilation in 10. Of the 48 first degree relatives of these 12 patients, tricuspid valve prolapse was diagnosed in 3, mitral valve prolapse in 15 and aortic root dilation in 12; aortic valve prolapse was not observed in any of these subjects. Of the 60 persons studied in these 12 kindreds, 28 (47%) had cardiac involvement. Among the 28 with cardiac involvement, aortic valve prolapse was observed in 1 (3.5%), tricuspid valve prolapse in 7 (25%), mitral valve prolapse in 27 (96%) and aortic root dilation in 22 (79%). Mitral valve prolapse was also present in the seven subjects with tricuspid valve prolapse and one with aortic valve prolapse. In 32 of the 60 persons studied in the 12 families, at least one abnormality of the cardiac, skeletal or ophthalmologic system was observed. Nineteen subjects were younger than 18 years of age; all had cardiac involvement associated with Marfan's syndrome. The notably earlier presentation of cardiac involvement in young persons may be responsible for a shorter life span in this group.(ABSTRACT TRUNCATED AT 250 WORDS)

Vasodilator therapy in chronic asymptomatic aortic regurgitation: enalapril versus hydralazine therapy.

OBJECTIVES: This study attempted to evaluate the long-term efficacy of enalapril versus hydralazine therapy on left ventricular volume, mass and function as well as on the renin-angiotensin system in chronic asymptomatic aortic regurgitation. BACKGROUND: We tested the hypothesis that early administration of a vasodilator drug might be able to reduce left ventricular dilation and mass expansion. Because the renin-angiotensin system may be activated in chronic aortic regurgitation, early enalapril therapy might be beneficial. METHODS: Between 1990 and 1993, 76 asymptomatic nonrheumatic patients with mild to severe chronic aortic regurgitation were enrolled in a randomized, double-blind trial comparing enalapril with hydralazine. All patients underwent serial noninvasive studies. Seventy patients completed the 12-month follow-up. RESULTS: At 1 year, patients receiving enalapril had a significant reduction in left ventricular end-diastolic and end-systolic volume indexes (124 +/- 15 vs. 108 +/- 17 ml/m2, p < 0.01; 50 +/- 12 vs. 40 +/- 14 ml/m2, p < 0.01, respectively) and mass index (131 +/- 16 vs. 113 +/- 19 g/m2, p < 0.01), whereas hydralazine therapy showed no significant changes. Both regimens not only had a significant reduction in left ventricular mean wall stress but also had a mild increase in exercise duration. Only enalapril therapy achieved a significant inhibition of the renin-angiotensin system, in contrast to hydralazine therapy. Moreover, the multiple r2 value from the analysis for end-diastolic volume index using the two variables of age and treatment drugs was 72.1% (p < 0.01). CONCLUSIONS: Both regimens decrease left ventricular mean wall stress. Enalapril therapy achieves significant left ventricular mass regression, left ventricular end-diastolic and end-systolic volume index reduction and renin-angiotensin system suppression. These findings suggest that early unloading enalapril therapy has the potential to favorably influence the natural history of chronic aortic regurgitation.

Accessory pathway and atrioventricular node reentrant tachycardia in elderly patients: clinical features, electrophysiologic characteristics and results of radiofrequency ablation.

OBJECTIVES: This study was designed to evaluate the clinical features, electrophysiologic characteristics and results of radiofrequency ablation in elderly patients with accessory atrioventricular (AV) pathways or AV node reentrant tachycardia. BACKGROUND: Radiofrequency ablation in elderly patients with paroxysmal supraventricular tachycardia has not been well described, and comparative study between elderly and younger patients is limited. METHODS: Electrophysiologic studies and radiofrequency ablation were performed in 92 elderly patients (45 with an accessory pathway, 47 with AV node reentrant tachycardia). RESULTS: The elderly patients had poorer electrophysiologic properties in accessory pathways and dual AV node pathways than those of younger patients. The success rate of radiofrequency ablation was similar in elderly and younger patients. However, elderly patients had more complications (14%) in left-sided accessory pathways. CONCLUSIONS: Radiofrequency ablation in elderly patients with supraventricular tachycardia was effective. However, it must be performed cautiously in those patients with left-sided accessory pathways.

Nadolol and supraventricular tachycardia: an electrophysiologic study.

To assess antiarrhythmic efficacy of oral nadolol, 15 patients with recurrent supraventricular tachycardia were studied. Eight patients had atrioventricular (AV) nodal reentrant tachycardia and seven had AV reciprocating tachycardia involving an accessory AV pathway. Electrophysiologic studies were performed before and after intravenous infusion of propranolol (0.20 mg/kg), and were repeated 5 to 8 days after oral nadolol therapy at a daily dose of 80 to 160 mg. Both intravenous propranolol and oral nadolol induced significant prolongation of the sinus cycle length from 741 +/- 73 ms to 834 +/- 97 and 1,029 +/- 95 ms, respectively (p less than 0.001 and p less than 0.0001, respectively). Both intravenous propranolol and oral nadolol depressed AV nodal but not accessory AV pathway conduction, and shifted the dual AV nodal pathway conduction curves (A1A2, A2H2; A1A2, H1H2) upward and to the right by prolonging the conduction time and increasing the refractory period. Ten patients (seven with AV nodal reentry and three with AV reciprocation) who responded to intravenous propranolol also responded to oral nadolol with loss of the inducibility of sustained tachycardia; the remaining five patients (one with AV nodal reentry and four with AV reciprocation) who did not respond to intravenous propranolol also failed to respond to oral nadolol with persistence of the inducibility of sustained tachycardia. Thus, in conclusion, intravenous propranolol testing predicts the therapeutic efficacy of oral nadolol therapy and oral nadolol in once-daily doses may be used for long-term prophylaxis of recurrent supraventricular tachycardia.

Electromechanical effects of caffeine in isolated human atrial fibres.

Effects of caffeine on the action potential and contractile force of human atrial fibres obtained at cardiac surgery were studied with standard microelectrode technique. In 4 mmol . litre-1 [K]o, the only significant action produced by 0.3 to 3 mmol . litre-1 caffeine on the electro-mechanical activity of relatively normal atrial fibres was a slight shortening of the action potential duration at 50% repolarisation. When the fibres were depolarised in 27 mmol . litre-1 [K]o or in atrial fibres showing slow responses in 4 mmol . litre-1 [K]o, however, caffeine could increase the upstroke of slow response and the force. In 18% of atrial fibres showing slow responses in 4 mmol . litre-1 [K]o, caffeine induced spontaneous discharges and potentiated afterdepolarisations. The positive inotropic and the arrhythmogenic effects of caffeine could be diminished by pretreating the fibres with propranolol or Ca antagonists (diltiazem and verapamil). In fibres beating spontaneously in normal [K]o, caffeine accelerated spontaneous rhythms initially and then depressed them. Propranolol potentiated the later depression but did not block the initial acceleration. The results suggest that caffeine increases the transmembrane Ca influx and enhances the release of Ca from the intracellular stores in human atrial fibres. As a consequence, caffeine could induce arrhythmias in atria from certain individuals.

Regional pulse wave velocities in hypertensive and normotensive humans.

STUDY OBJECTIVE: The aim was to compare regional wave transmission and reflection properties along the aorta in age matched normotensive and hypertensive subjects. DESIGN: Simultaneous upstream and downstream micromanometer pressures were recorded at five regions from the ascending aorta to the iliac artery. Recordings were made in the baseline condition in both groups and during sustained isometric handgrip exercise in the normotensives to see if increasing the blood pressure to hypertensive levels would eliminate baseline differences between the two groups. SUBJECTS: Only subjects who had no coronary or valvular heart disease were studied. Normotensive subjects (n = 8) were selected from those undergoing electrophysiological testing whose blood pressures were consistently in the normal range (systolic less than 140, diastolic less than 90 mm Hg). Age matched hypertensive subjects (n = 17) were those in whom secondary causes of hypertension were excluded and who had repeated measurements of raised blood pressure. MEASUREMENTS AND RESULTS: In each region pulse wave velocity was estimated from the simultaneous upstream and downstream pressure records using the foot to foot method, and apparent phase velocity was obtained from Fourier analysis of the two pressures. The intensity of wave reflections was judged by the magnitude of fluctuations of the harmonics of apparent phase velocity about the mean of the higher frequency harmonics. In both groups in the baseline state there were regional variations in the pulse wave velocity with the lowest values occurring just proximal to the renal arteries and highest values occurring in the iliac artery. Likewise, in both groups the extent of wave reflections varied regionally--pronounced reflections were seen in the ascending aorta and from just proximal to the renal arteries to the aortic bifurcation but not in the mid-thoracic or iliac regions. The hypertensives had higher pulse wave velocity than normotensives only in the iliac artery (780 v 567 cm.s-1) and had more reflections in the three regions in which reflections were evident. Although handgrip in the normotensive group eliminated regional differences in pulse wave velocity between the groups, reflections were still greater in the hypertensives. CONCLUSIONS: Essential hypertension affects the regional properties of the aortic wall. These alterations are manifested by increased peripheral wave-speed and increased wave reflections along the aorta. The differences in wavespeed but not reflection properties are eliminated when the pressures are matched by handgrip, suggesting that factors other than the level of blood pressure per se are responsible for the alterations in reflection properties.

The influence of verapamil and nifedipine on hepatic indocyanine green clearance in patients with HBsAg-positive cirrhosis and ascites.

The influence of verapamil and nifedipine on hepatic indocyanine green kinetics was studied in 12 patients with HBsAg-positive cirrhosis and ascites. Hepatic clearance and its two biologic determinants, hepatic blood flow and metabolic activity (intrinsic clearance [maximum velocity/metabolite elimination rate constant, or Vmax/km]), were determined from hepatic indocyanine green elimination at steady state in patients with cirrhosis. Acute intravenous administration 10 mg verapamil significantly increased the hepatic indocyanine green blood flow (p less than 0.05), but significantly decreased the hepatic clearance (p less than 0.05), extraction ratio (p less than 0.05) and Vmax/km (p less than 0.05). However, acute sublingual administration of 10 mg nifedipine resulted in no significant change in any parameters of hepatic elimination function. These results show that verapamil, but not nifedipine, might impair the transhepatic extraction activity of hepatocytes in patients with HBsAg-positive cirrhosis and ascites.

Performance on a dementia screening test in relation to demographic variables. Study of 5297 community residents in Taiwan.

OBJECTIVE: To examine the relation between performance on a dementia screening test and the demographic variables of age, education, gender, and urban vs rural residency. DESIGN: Community survey with cluster sampling. SETTING: One urban and one rural community from each of four geographic regions in Taiwan, Republic of China. PARTICIPANTS: A total of 5265 nondemented individuals approximately equally divided between men and women and between urban and rural residency with a range in age from 41 to 88 years and in education from 0 to 20 years. MAIN OUTCOME MEASURE: Score on a Chinese adaptation of the Mini-Mental State Examination. RESULTS: Lower test scores were associated with older age and less education. The decrease in score with age was faster among participants who had never attended school. Better performance by men and by urban residents was found only among participants with fewer than 6 years of schooling. In this group, the magnitudes of sex and residency differences were comparable among those subjects aged 41 to 64 years and those aged 65 to 88 years. Women who had never worked outside of the home performed poorer than those who had worked outside of the home. CONCLUSIONS: The influence of educational background on test performance is most evident in individuals with less education. Commonly used dementia screening tests may be unfair to poorly educated individuals, especially women and rural residents. Efforts should be made to develop ecologically relevant cognitive tests for the intended study populations. To help distinguish test bias from different rates of cognitive decline, the study populations should include individuals in predementia age ranges.

Plasma lipid profiles and epidemiology of atherosclerotic diseases in Taiwan--a unique experience.

Rapid economic growth in Taiwan is accompanied by changing lifestyles, and the mortality pattern has switched from predominantly infectious diseases to chronic diseases. Age-adjusted mortality from heart disease has increased slowly but steadily. However, mortality from heart disease in Taiwan remains low compared with many other countries. Mortality from the cerebrovascular diseases has decreased gradually. Current age- and sex-specific values of blood cholesterol low density lipoprotein cholesterol (LDL-C) and triglyceride (TG) are, in general, higher than values in mainland China, but lower than those in the NHANES III and PROCAM studies. From 1950 to 1987, percent dietary fat increased from 16% to 36% in Taiwan. However, a high polyunsaturated fat/saturated fat (P/S) ratio (1.3) maintained during this period may in part explain the favorable blood lipid status and low mortality from heart disease. Data from prospective studies are scarce. In case-control studies carried out in Chinese, significantly higher values of TG, CHOL LDL-C, but lower high density lipoprotein cholesterol (HDL-C) levels have often been found in coronary artery disease (CAD) patients than in controls. The percent differences in TG and HDL-C values (20%) were much greater than those of CHOL and LDL-C (3%). A few studies have identified the TG level as an independent risk factor for stroke and CAD in Taiwan, where a moderate to high fat diet with an advantageous P/S ratio is consumed.

Frequency and severity of mitral regurgitation one year after balloon mitral valvuloplasty.

Mitral regurgitation (MR) was evaluated by Doppler echocardiography in 59 patients with mitral stenosis before, immediately after and 1 year after balloon mitral valvuloplasty (BMV). The severity of MR was graded on a scale from 1+ to 4+. Echocardiographic and hemodynamic variables were analyzed to study the potential factor(s) that might predict the long-term persistence of MR. Echocardiographic variables were mitral valve thickness and motion, subvalvular change, left atrial dimension, commissural calcification and effective balloon/mitral anular diameters. Hemodynamic variables were mitral pressure gradient, pulmonary arterial pressure, ejection fraction, mitral valve area index, age, gender and cardiac rhythm. Mitral valve area index increased from 0.9 +/- 0.5 to 1.5 +/- 0.8 cm2/m2 immediately after BMW, and to 1.4 +/- 0.3 cm2/m2 at 1 year follow-up (p less than 0.01). Immediately after BMV, MR grading did not change in 30 patients (51%), increased by 1+ in 23 patients (39%), by 2+ in 2 patients (3.3%) and by 3+ in 2 patients (3.3%), and decreased by 1+ in 2 others. At 1-year follow-up, only 1 patient with severe MR required valve replacement. Fifty-one patients (88%) had no change in the extent of MR (less than or equal to 1+) and 6 patients (10%) had a 1-grade decrease in their MR; only 1 patient had a 1-grade increase in MR. No clinical or hemodynamic variables or morphologic characteristics of the mitral valve could predict the development of significant MR after BMV. It is concluded that an increment in MR severity less than or equal to 2+ is frequently seen after BMV.(ABSTRACT TRUNCATED AT 250 WORDS)

Termination of digitalis-induced ventricular tachycardias by clonidine involves central alpha 2-adrenoceptors in cats.

1. Effects of intravenous (i.v.) and intravertebral arterial (i.a.) administration of the alpha 2-adrenoceptor agonist, clonidine (Clon) and its antagonist, yohimbine (Yoh, 0.5 mg kg-1, i.v.; 0.05 mg kg-1, i.a.), on ventricular tachycardia (VT) induced by intravenous acetylstrophanthidin (AS) were studied in cats anaesthetized with intraperitoneal chloralose. 2. AS dose-dependently produced cardiac arrhythmias including complete atrioventricular conduction block (118 +/- 14 micrograms kg-1, i.v.), junctional tachycardia (128 +/- 20 micrograms kg-1, i.v.), multiform ventricular premature beats (157 +/- 21 micrograms kg-1, i.v.) and sustained VT (220 +/- 23 micrograms kg-1, i.v.). 3. Doses of Clon (i.v.) required for termination of VT following i.v. Yoh (62.9 +/- 5.2 micrograms kg-1) or i.a. Yoh (88.5 +/- 16.3 micrograms kg-1) were higher than those for termination of VT without Yoh administration (28.3 +/- 6.2 micrograms kg-1). Doses of Clon (i.a.) required for termination of VT without or with i.a. Yoh administration were 5.8 +/- 1.0 or 14.8 +/- 3.7 micrograms kg-1, respectively, and they were significantly different. 4. These experiments demonstrate that either i.v. or i.a. Yoh antagonizes the antiarrhythmic effect of Clon on AS-induced VT. Since small doses of Clon administered i.a. act predominantly on the central nervous system, we suggest that its antiarrhythmic effect is likely to be on central alpha 2-adrenoceptors in the central nervous system.

Inhibition of the mitochondrial Mg2+-ATPase by propranolol.

The in vitro effects of propranolol, a commonly used beta-adrenergic blocker, on the membrane structure and function of rat heart mitochondria were investigated. It was found that the respiratory control and oxidative phosphorylation of the isolated mitochondria decreased concomitantly when the drug was added to the assay medium. At the concentration higher than 1.0 X 10(-4) M, propranolol significantly inhibited the State 3 respiration but had little effect on the State 4 respiration of the mitochondria. On the other hand, the drug exhibited noncompetitive inhibitions toward the Mg2+-ATPase activity of submitochondrial particles and purified enzyme preparations at the concentrations ranging from 3.0 X 10(-4) to 1.5 X 10(-3) M. The inhibitory constants of propranolol toward the enzyme activity in submitochondrial particles and in the purified preparation were estimated to be 6.7 X 10(-4) and 1.4 X 10(-3) M, respectively. However, the drug did not show significant effect on the activity of any of the enzyme complexes of the mitochondrial respiratory chain. It is thus concluded that propranolol impairs the mitochondrial respiration and oxidative phosphorylation mainly through its inhibition of the Mg2+-ATPase activity of the mitochondria. This effect of propranolol may explain, at least partly, its depression effects on the cardiac functions of the animal.

Surface marker analysis of acute lymphocytic leukaemia in Taiwan, Republic of China.

Acute lymphocytic leukaemia (ALL) is heterogeneous in clinical characteristics and immunological properties. Standard surface marker analysis has enabled us to subclassify 121 cases of ALL into four subtypes, i.e. T-ALL, common ALL, null ALL and B-ALL. We have also tried to correlate these subtypes with their clinical characteristics. Our patients had younger ages with a mean age of 13.75. A slight male predominance was observed. There were consistently higher incidences in northern Taiwan in each subtype, but no significant differences in incidences between rural and urban areas. Although there were high incidences of L1 type cell in each immunological subtype, there was no correlation between FAB classification and each subtype, nor did morphologic features relate to cellular origins. Clinical manifestations revealed significantly high incidence of CNS involvement and thymic mass in T-ALL. Hepatosplenomegaly was more common and complete remission rate was higher in children with ALL than in adults.

Immunological classification of T-cell acute lymphoblastic leukaemia using monoclonal antibodies.

We had been able to classify 70 cases of acute lymphoblastic leukemia (ALL) into different immunological subtypes based on surface marker analysis with the aid of a panel of monoclonal antibodies. The relative proportions of different ALL subclasses appears to be similar to those reported from Europe and the U.S.A. Our results also indicated that monoclonal antibodies OKT11, UCHT-2 and WT1 were very useful in defining pre-T or early T subtypes of ALL. The latter leukaemias lack most maturation-linked T-cell markers but share with the other T-ALL the characteristic of low density or undetectable insulin receptors.

Coronary spasm complicating sclerotherapy of esophageal varices.

There are rare serious cardiac complications associated with endoscopic examination. An episode of coronary artery spasm developed in a 68-year-old man during endoscopic sclerotherapy for esophageal varices. The coronary artery spasm may have been triggered by a reflex increase in sympathetic discharge under stressful circumstances, and may occur most often in patients with preexisting heart disease. In patients with severe cardiac disease, ECG monitoring during the procedure seems justified.

Reappraisal of continuous positive airway pressure therapy in acute cardiogenic pulmonary edema. Short-term results and long-term follow-up.

To investigate whether serial incremental continuous positive airway pressure (CPAP) has any short-term or long-term advantages over face-mask oxygen therapy by way of intrapulmonary shunt reduction, 100 patients admitted to the coronary care unit for the treatment of acute cardiogenic pulmonary edema were studied. All patients received Swan-Ganz catheterization. Hemodynamic and pulmonary function parameters were recorded over the next 6 h, and the patients were followed until hospital discharge. All survivors received regular follow-up at 1-month intervals in the outpatient clinic. During the first-stage investigation period (3 h) PaO2 in the CPAP group showed a significant increase, whereas the intrapulmonary shunt and alveolar-arterial oxygen tension gradient (P[A-a]O2) was significantly reduced (p < 0.005). The CPAP group had significantly lower rate-pressure product and higher stroke volume index compared with the control group. The therapeutic failure rate over 6 h was 24% in the CPAP group and 50% in the control group (p < 0.01). The CPAP group had a significantly lower incidence of tracheal intubation and ventilator therapy than the control group; however, there was no significant difference in short-term mortality and hospital stay between the two groups. In conclusion, although study size was not large enough to demonstrate a difference in mortality, CPAP therapy resulted in physiologic cardiovascular and pulmonary function improvement and significantly reduced the need for intubation; however, it did not decrease mortality in patients with acute cardiogenic pulmonary edema, and a much larger study is needed to investigate this possibility.

Prevalence and subtypes of dementia in Taiwan: a community survey of 5297 individuals.

OBJECTIVE: To study the prevalence rate of dementia in Taiwan, the relative frequencies of its subtypes, and its associations with age, education, gender, and residence location. PARTICIPANTS: A total of 2753 men and 2544 women from four urban and four rural communities participated. Their age ranged from 41 to 88 years; 28% of them were at least 65 years old. Their education ranged from 0 to 20 years; 27% of them had less than 1 year of formal schooling. DESIGN: Phase I was a screening survey by trained nurses who administered a Chinese version of the Mini-Mental State Examination, the MMSE-T1, to all participants. Phase II involved the assessment for dementia by neurologists on the 1521 individuals who had scored less than 24 on the 30-point MMSE-T1. MAIN RESULTS: Thirty-one cases of dementia were identified by the DSM-III-R criteria, including 18 cases of Alzheimer's disease, 10 cases of vascular dementia, and three cases of other dementias. The prevalence rate in individuals aged 65 and over was 2.0%. Aging and illiteracy were associated with higher rates of dementia; gender and residence location made no difference. CONCLUSIONS: The prevalence rate of dementia was low in this Chinese population. Consistent with common findings from other parts of the world, a high rate of dementia was associated with older age and illiteracy, and Alzheimer's disease was the most frequent cause.

Evidence for a delayed, integral, and proportional phase of glucocorticoid feedback on ACTH secretion in normal human volunteers.

To investigate the mechanisms responsible for glucocorticoid feedback on nonstress-induced ACTH secretion in normal subjects, 24 volunteer subjects (14 males and 10 females, 21 to 43 years) were divided into six groups in a randomized fashion and studied. Each subject received a single midnight dose of 30 mg/kg per body weight of metyrapone and then cortisol was administered according to different protocols in the next morning to provide extreme variations of the input signal. It was found that no obvious inhibition in plasma ACTH levels was shown during the first 15 min despite the fact that cortisol was given at rather larger doses and short time intervals. However, a significant suppression in plasma ACTH levels began to manifest approximately 30 min after cortisol administration in each study group and it became apparent that the degree of inhibition of ACTH level at 75 min correlated with the plasma cortisol concentrations at the same moment (r = 0.97, P less than 0.01) as well as with the dosage of cortisol during this time, whatever administered (r = 0.99, P less than 0.01). In summary, our data provided evidence for a delayed, proportional, and integral phase of glucocorticoid feedback on nonstress-induced ACTH secretion in normal human volunteers.