Keiko Uezono

A simple method for estimating 24 h urinary sodium and potassium excretion from second morning voiding urine specimen in adults.

1. An assessment was made of the extent sodium (Na) and potassium (K) intake can be estimated from Na, K and creatinine (Cr) content of a second morning voiding urine (SMU) specimen collected within 4 h after the first voiding upon awakening but before breakfast in 159 clinically healthy, free‐living individuals (20–79 years). The SMU and the rest of 24 h urine specimens for a 3–5 day period were collected.

A school refusal case with biological rhythm disturbance and melatonin therapy

An 18-year-old male high school student with school refusal and circadian rhythm disturbance is reported. At 17 years of age, he was unable to attend school because of a reversal of the daily rhythm and a moderate depressive feeling. Other circadian rhythms, including deep body temperature (DBT), and plasma melatonin, cortisol and beta-endorphin, also showed quite different or abnormal curves compared with those in normal controls. He was treated with methyl B12 and melatonin, which normalized the circadian rhythm, i.e. it became entrained to a 24-h period, and the DBT and hormonal rhythms became closer to normal patterns. These results suggest that desynchronization of the biorhythms, particularly the circadian rhythm, may be one of the important causes of school refusal in Japan, and melatonin and methyl B12 might be useful for treatment of the condition.

Circadian Variations of Urinary Dopamine, Norepinephrine, Epinephrine and Sodium in Normotensive and Hypertensive Subjects

Under standardized conditions, we determined circadian urinary excretion of sodium (Na) and free dopamine (DA), norepinephrine (NE) and epinephrine (E) in 20 normotensive, 20 borderline hypertensive and 10 mild hypertensive middle-aged men. The 24-hour excretions of water, Na, DA, NE and E were comparable between the normotensives and the hypertensives. In the total study population, these parameters showed significant time-related changes: high excretion during the daytime and low excretion in the night. The circadian variations of urinary DA, NE and E were similar among the 3 groups. The circadian curve of urinary DA was similar to those of Na and water excretion. In the total study population, 24-hour water and Na excretion correlated positively with urinary DA, but not with NE or E. These results suggest that endogenous DA may play a role in the circadian variation of water and sodium metabolism. The circadian excretion of urinary catecholamines may not be altered in middle-aged subjects with borderline or mild hypertension.

Antihypertensive effect of E-643, a new alpha-adrenergic blocking agent

SummaryTo determine whether E-643, a new α-blocking agent, would reduce the blood pressure, regardless of the posture, a 1 mg dose was given 3 times daily for 7 consecutive days, to 8 male and 7 female inpatients, aged 37–73 years, with essential hypertension. Blood pressure and pulse rate were measured daily in the supine, sitting and standing positions. Before and after the treatment with E-643, plasma levels of noradrenaline, adrenaline, dopamine-β-hydroxylase, renin and aldosterone were determined, samples being obtained with the subjects recumbent and after standing upright for 60 min. A significant reduction in the systolic and diastolic blood pressures was evident in the supine (172±31/100±12 → 151±28/89±14 mmHg), sitting (158±22/101±11 → 138±28/89±15 mmHg) and standing (153±32/103±21 → 129±31/89±20 mmHg) positions. The reduction in blood pressure remained unchanged throughout the period of administration of E-643. Pulse rate was not affected when the subjects were supine (67±10 → 69±10 beats/min), but was increased in the sitting (68±10 → 73±9 beats/min) and standing (73±10 → 81±11 beats/min) positions. The increased pulse rate tended to decline during continued administration of E-643. Treatment with E-643 produced no significant change in plasma levels of adrenaline, noradrenaline, dopamine-β-hydroxylase, renin and aldosterone. The antihypertensive effect of treatment was more prominent in the patients with higher levels of plasma catecholamines and dopamine-β-hydroxylase, and was less prominent in those with higher plasma renin and aldosterone. Two patients had temporary bouts of dizziness and visual disturbances, but there were no subjective complaints during treatment.

Differences and similarities among circadian characteristics of plasma renin activity in healthy young women in Japan and the United States

A circadian rhythm of plasma activity (PRA) was demonstrated for both Japanese and North American women, the latter mostly Caucasians of mixed ethnic origin. The results were based on blood samples withdrawn at 4-hour intervals during a 24-hour span (in March 1978) from 20 subjects from Fukuoka (average age 20.4 +/- 0.1 years) and 16 subjects from Minneapolis (average age 20.2 +/- 0.4 years). The rhythms in the two populations showed similarities in some characteristics and differences in others. The timing of high values, i.e., of acrophases, objectively assessed by curve-fitting (and of corresponding 95 per cent confidence limits) was at 07(36) (05(00), 10(16) and 06(32) (03(00), 10(00) for Japan and USA, respectively. As objective measures of the extent of predictable rhythmic change mean amplitudes, in nanograms per milliliter per hour (ng/ml/hour), were similar (0.31 and 0.32); a statistically significant difference (P less than 0.05) was found in mean amplitudes expressed as percentage of the rhythm-adjusted average. Mean rhythm-adjusted average values (mesors) were lower in women from Japan than in those from the United States: (1.64 +/- 0.14 and 2.39 +/- 0.23 ng/ml/hour, respectively; P less than 0.01). A statistically significant difference in dietary salt, indicated by differences between the Japanese and North American women in the urinary excretion of sodium and chloride (P less than 0.05), almost certainly contributed to these results.

Circadian Characteristics of Urinary Epinephrine and Norepinephrine from Healthy Young Women in Japan and USA

Clinically healthy diurnally active young adult women were studied during the same season (March) at the Universities of Kyushu (Fukuoka City, Japan) and of Minnesota (Minneapolis, U.S.A.), under comparable conditions, except that the habitual diets were not changed. The subjects (20 Japanese and 16 Americans of mixed Caucasian background) were studied over a single 24-hr span. Urine was collected at 4-hr intervals. A circadian rhythm in total urinary norepinephrine excretion showed similar characteristics in Japanese and Americans. In epinephrine excretion, the Japanese women showed a statistically significantly higher amplitude with higher peak values, but no statistically significant difference in the rhythm-adjusted mean. This intergroup difference is strictly time dependent; it does not come to the fore in urine samples covering the nocturnal rest span of the subjects.

Is single oral administration of captopril beneficial in screening for primary aldosteronism

Plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were measured in 19 cases with primary aldosteronism (PA) and in 72 with essential hypertension (EHT) to differentiate the two disorders during the following conditions on normal salt diet: after overnight recumbency (basal state) and 2 hours after oral administration of 25 mg of captopril. Screening criteria were determined so that all PA patients were diagnosed as positive, and their specificities were compared with those of other conventional screening methods for PA. After captopril administration, the specificity of a criterion based on a combination of PAC and PAC/PRA ratio was 93% and positive predictive value was 79%. This criterion was superior to blood pressure response to angiotension II analog infusion, PRA on salt depletion, and to PAC on salt loading. However, higher specificity (97%) and positive predictive value (90%) were obtained from a criterion based on a combination of basal PAC and PAC/PRA ratio. Therefore, the use of a combination criterion based on PAC and PAC/PRA ratio at basal state rather than after captopril administration may give a satisfactory result in the screening for PA.

Impact of antihypertensive medication adherence on blood pressure control in hypertension: the COMFORT study

BACKGROUND It has not been fully elucidated whether antihypertensive medication adherence affects blood pressure (BP) control in hypertension cases. AIM To investigate the association of adherence to antihypertensive drug regimens and BP control using data from the Combination Pill of Losartan Potassium and Hydrochlorothiazide for Improvement of Medication Compliance Trial (COMFORT) study. DESIGN An observational analysis from a randomized controlled trial. METHODS A total of 203 hypertensive subjects were randomly assigned to a daily regimen of a combination pill (losartan 50 mg/hydrochlorothiazide 12.5 mg) or two pills, an angiotensin II receptor blocker and a thiazide diuretic. Medication adherence calculated based on pill counts and BPs was evaluated at 1, 3 and 6 months after randomization. RESULTS The subjects were divided into three groups according to their adherence, i.e. relatively low-adherence (<90%; n = 19), moderate-adherence (90-99%; n = 71) and high-adherence (100%; n = 113) groups. Clinical characteristics of the subjects including BP, sex, randomized treatments and past medical history did not differ significantly among the three groups. Achieved follow-up BPs over the 6-month treatment period, which were adjusted for age, sex, baseline BP and randomized treatment, were significantly higher in the low-adherence group (135/78 mmHg) compared with the high-adherence (130/74 mmHg; P = 0.02/0.02) and the moderate-adherence (128/74 mmHg; P = 0.003/0.02) groups. CONCLUSION Low adherence to an antihypertensive-drug regimen was associated with poor BP control.

Circadian variations of plasma atrial natriuretic peptide in four types of hypertensive disorder during pregnancy

Summary. Circadian variations in plasma atrial natriuretic peptide were studied, to clarify the characteristic pathophysiology of pregnancy‐induced hypertension (PIH). The mean 24‐h values (range) of atrial natriuretic peptide in mild and severe PIH, pregnancy‐aggravated hypertension, chronic hypertension and normal pregnancy were 130·1 (97·3−207·0), 225·4 (202·8−281·8), 213·1 (183·2−249·5), 81·3 (61·8−116·1) and 77·1 (56·0−123·5) pg/ml, respectively. The values in PIH and pregnancy‐aggravated hypertension were significantly higher, although those in chronic hypertension were no different from normal pregnancy. Plasma atrial natriuretic peptide showed a clear circadian rhythm with acrophase in the middle of the night, in mild and severe PIH. In the other hypertensive disorders, a circadian rhythm could not be confirmed. The results indicate that the elevated values of plasma atrial natriuretic peptide in hypertensive disorders during pregnancy relate to generalized vasoconstriction, and that the diurnal rhythm is a specific characteristic of PIH.

Improvement of blood pressure control in a hypertension clinic: a 10-year follow-up study.

The objective of the study was to assess whether the publication of new guidelines, such as JNC VI 1997 and WHO/ISH 1999, and the development of new antihypertensive drugs have improved blood pressure (BP) control. A total of 150 patients (age 29–88, mean 66±11 years in 2001) who were followed at our hypertension clinic during 1991–2001 were retrospectively investigated. We compared the clinical characteristics of the patients in 2001 to those in 1991 and 1996, using the averaged BP determined at two occasions each year for our analysis. The average BP decreased during the 10 years between 1991 and 2001. When good BP control was defined as <140/90 mmHg, the rate of patients with good BP control increased from 31% in 1991 to 43% in 1996, and to 57% in 2001 (P<0.001 vs 1991). Both younger (⩽64 years) and older (⩾65 years) patients showed similar improvement during these 10 years. In 2001, satisfactory BP control (<130/85 mmHg) was achieved in 24% of younger patients, which was significantly higher than the achievement in 1991 (10%, P=0.02). This improvement occurred at the same time as an increase in the prescription of Ca antagonists and angiotensin II antagonist. The patients with improved BP control during these 10 years (n=50) showed lower body mass index (BMI) and serum total cholesterol levels in 2001 compared to persistently uncontrolled patients (n=54). Furthermore, the change in BMI during these 10 years was significantly less in the patients with improved BP control than in the persistently uncontrolled patients. In conclusion, BP control improved in the 10 years studied, and it seems to be attributable to the more frequent use of the newer drugs such as angiotensin II antagonists and Ca antagonists, to lifestyle modification and also to the growth in awareness of the importance of strict BP control.