Biomedical subjects
Publications and source records attributed to P K Zachariah.
Adverse effects of amlodipine besylate, a widely used antihypertensive medication, include peripheral edema, flushing, headache, pruritus, and rash. An adverse renal effect attributable to the medication has hitherto not been reported in the literature. We herein report a case of amlodipine besylate induced acute interstitial nephritis.
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OBJECTIVES: We sought to determine the efficacy of isradipine in reducing left ventricular (LV) mass and wall thickness in hypertensive patients. BACKGROUND: LV hypertrophy on the echocardiogram is a strong predictor of cardiovascular events. Reduction of LV mass may be a desirable goal of drug therapy for hypertension. However, although thiazide diuretic drugs have been advocated as first-line therapy for hypertension, their efficacy in reducing LV mass has been questioned. METHODS: Patients with mild to moderate diastolic hypertension and LV mass in excess of 1 SD of normal values were randomized to isradipine (n = 89) or hydrochlorothiazide therapy (n = 45). Evaluations were obtained at baseline, after 3 and 6 months of treatment and 2 weeks after treatment was stopped. RESULTS: At 6 months, LV mass decreased by 43 +/- 45 g (mean +/- SD) with hydrochlorothiazide (p < 0.001) but only by 11 +/- 48 g with isradipine (p = NS; between-group comparison, p < 0.001). Two weeks after drug therapy was stopped, LV mass remained 24 +/- 41 g lower than that at baseline in the hydrochlorothiazide group (p = 0.003) but only 7 +/- 50 g lower in the isradipine group (p = NS). Septal and posterior wall thicknesses were significantly and equally reduced with both isradipine and hydrochlorothiazide. Greater LV mass reduction with hydrochlorothiazide was related to a 2.8 +/- 3.3-mm reduction of LV cavity size with hydrochlorothiazide but no reduction with isradipine. At 6 months of treatment, diastolic blood pressure (BP) by design was equally reduced in both treatment groups. At 3 months, systolic BP was reduced by 17 +/- 15 mm Hg with isradipine and by 26 +/- 15 and 25 +/- 17 mm Hg at 3 and 6 months, respectively, with hydrochlorothiazide (p = 0.003, between-group comparison). However, on stepwise multivariable regression analysis, treatment selection (partial r2 = 0.082, p = 0.001), change in average 24-h systolic BP (partial r2 = 0.032, p = 0.029) and change in average sitting systolic BP (partial r2 = 0.017, p = 0.096) were predictive of LV mass reduction. CONCLUSIONS: Despite an equivalent reduction of diastolic BP, 6 months of therapy with hydrochlorothiazide is associated with a substantial reduction of LV mass, greater than that with isradipine. The superior efficacy of hydrochlorothiazide for LV mass reduction is associated with a greater reduction of systolic BP as well as drug selection itself. These data may have important therapeutic implications.
OBJECTIVE: In this study, we determined the effect of age, sex, and body size on left ventricular mass. DESIGN: Two-dimensional-guided M-mode echocardiography was used in an assessment of 111 healthy, normal adults. MATERIAL AND METHODS: Left ventricular mass was calculated with the cube function formula corrected by a regression equation to agree with autopsy estimates of left ventricular mass. Calculated left ventricular mass, indexed by body surface area and by height, was analyzed on the basis of sex and age of the study participants. Age was analyzed as a dichotomous, trichotomous, and continuous variable. The effects of age, sex, and obesity, as well as interactions, were tested within a multiple linear regression model framework. RESULTS: Left ventricular mass, when indexed for either body surface area or height, was greater in men than in women. For women, but not men, we found a small but significant increase in left ventricular mass with advancing age. Body mass index, an indicator of obesity, increased with aging in women but not in men and affected left ventricular mass. No significant changes were noted in left ventricular cavity size with advancing age, and the increase in left ventricular mass in women was due to increased ventricular wall thickness. CONCLUSION: The findings in this study suggest that left ventricular mass, as assessed by two-dimensional-guided M-mode echocardiography, is affected not only by sex and body size but also by age in women. This phenomenon may be related to an increase in body mass index with advancing age in women. In clinical studies that use echocardiographic left ventricular mass to diagnose left ventricular hypertrophy, these observations should be considered.
OBJECTIVE: To determine standard left ventricular Doppler measurements in a large reference group of various ages to reflect the senescence process. DESIGN: We prospectively studied the influence of aging on left ventricular diastolic filling by performing Doppler echocardiography in 117 normal healthy volunteers. MATERIAL AND METHODS: Transthoracic pulsed-wave Doppler echocardiographic studies of pulmonary venous flow and left ventricular inflow were done in the 53 male and 64 female study subjects. For analysis, the study subjects were arbitrarily classified into two groups: those younger than 50 years of age (group 1; N = 61) and those 50 years old or older (group 2; N = 56). RESULTS: A striking difference was found in pulmonary venous flow and left ventricular inflow between group 1 and group 2 subjects. Group 2 had increased pulmonary venous peak systolic flow velocity (71 +/- 9 versus 48 +/- 9 cm/s), decreased peak diastolic flow velocity (38 +/- 9 versus 50 +/- 10 cm/s), increased peak atrial reversal flow velocity (23 +/- 4 versus 19 +/- 4 cm/s), and increased percentage of forward flow in systole (65 +/- 7 versus 55 +/- 8%) in comparison with group 1. In group 2, peak early filling velocity (62 +/- 14 versus 72 +/- 14 cm/s) and ratio of early filling to atrial filling (1.1 +/- 0.3 versus 1.9 +/- 0.6) were lower and peak atrial filling velocity (59 +/- 14 versus 40 +/- 10 cm/s) was higher than in group 1. Deceleration time (210 +/- 36 versus 179 +/- 20 ms) and isovolumic relaxation time (90 +/- 17 versus 76 +/- 11 ms) were prolonged in group 2 in comparison with group 1. CONCLUSION: This study confirms the major influence of the aging process on left ventricular diastolic function in a large series of normal subjects. This physiologic factor should be considered in Doppler assessment of left ventricular diastolic filling in future studies.
Left ventricular (LV) filling was studied in 18 healthy subjects and 19 mildly hypertensive patients before and after 50% and 70% of maximal supine exercise using radionuclide ventriculography. In addition, in the hypertensive patients, the effects of oral verapamil and lisinopril treatment on LV filling before and after exercise were studied. At rest, hypertensive patients compared with healthy subjects had a lower peak filling rate, ratio of peak filling to peak emptying rate, first-half filling fraction, and a longer isovolumic duration. With exercise, LV filling measures were not different between healthy subjects and hypertensive patients. In the hypertensive patients at rest, compared with before treatment, lisinopril prolonged isovolumic duration and verapamil had no effect on LV filling; at 50% maximal exercise compared with before treatment, verapamil shortened the time to peak filling rate and isovolumic duration and increased first-half filling fraction but, at 70% maximal exercise, verapamil had no effect, whereas lisinopril did not alter exercise LV filling at either exercise level. Thus, the early abnormal LV filling in mildly hypertensive patients is influenced by therapeutic interventions both at rest and with exercise.
The feasibility of substituting a shorter duration of ambulatory blood pressure monitoring (ABPM) for 24h ambulatory monitoring to evaluate increased office BP measurements was investigated by analysing the records of 126 normal volunteers and 168 mildly hypertensive patients receiving placebo, including 22 studied on two occasions two months apart. The value to be predicted was the long-term awake BP mean for an individual (usual BP). Among the subjects studied on two occasions, there were no systematic differences between the two occasions and there was reasonable correspondence between the hourly patterns. Estimated variance components were substituted in a formula for the standard error of prediction (SEP) of the usual awake mean BP, for various durations and frequencies of monitoring. The lower limit of the SEP was determined by the patient-by-occasion component of variance. As few as six hours of monitoring with two to three readings/hour achieved most of the gain in precision obtainable by going from single BP readings toward continuous measurement during an entire awake period. In the remaining subjects, the influence of the day rhythm of BP on short-term monitoring was examined by measuring the differences in means of 6h periods from the full awake mean BP for starting times from 7 am to 3 pm. Among normotensives and hypertensive patients with near normal office BP (< 144/< 96 mmHg), there was little difference due to starting time. There was, however, a slight positive bias in the more hypertensive subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
The variability of blood pressure and its consequences suggests that ambulatory blood pressure (ABP) data should be analyzed not only by mean ambulatory blood pressure (MABP), but also by looking at blood pressure load (BPL, the percentage of measurements > 140/90 mm Hg while awake and > 120/80 while asleep). In one study, several hypertensive patients whose ambulatory diastolic blood pressure was < 90 mm Hg had a diastolic load near 50%. Studies have reported strong correlations between BPL and indices of target-organ changes such as left ventricular mass index (LVMI). It was necessary to lower office blood pressure to < 85 mm Hg to reduce BPL to a normal range of 15 to 20%. To further investigate the usefulness of BPL in the study of hypertension, more longitudinal studies of cardiovascular disease and blood pressure variability are needed.
Ambulatory blood pressure monitoring has become increasingly popular for diagnosing and treating hypertension. However, data from normotensive subjects are needed for interpretation of hypertensive readings. Ambulatory blood pressure was monitored in 126 normotensive subjects (age range, 20 to 84 years). Mean systolic and diastolic blood pressure and blood pressure loads (percentage of systolic readings greater than 140 mm Hg and diastolic readings greater than 90 mm Hg) were obtained and interpreted. Mean awake systolic and diastolic pressures ranged from 125 +/- 10 to 137 +/- 17 mm Hg and 70 +/- 8 to 71 +/- 9 mm Hg, respectively. The systolic and diastolic trends of subjects' blood pressures taken during office visits and the 24-hour measurements were similar. Ranges for systolic and diastolic blood pressure loads from youngest to oldest ages were 9% +/- 14% to 25% +/- 20% and 3% +/- 7% to 4% +/- 7%, respectively. A comparison of blood pressure means from our sample that were taken during office visits and blood pressure means from a 2122-patient community survey demonstrated that our sample was reflective of an unselected population.
The pharmacokinetics of verapamil were studied in patients with renal failure who were undergoing maintenance hemodialysis and in normal subjects after an IV infusion of 10 mg and a single oral dose of 120 mg. Plasma levels of verapamil and its active metabolite, norverapamil, were analyzed by a sensitive and specific HPLC procedure. Severe renal failure requiring hemodialysis did not change the time course of verapamil and norverapamil plasma concentrations after either the IV or oral dose. The terminal elimination rate constant, clearance, volume of distribution, and bioavailability of verapamil were not significantly different between the two groups of subjects. In addition, the apparent maximal plasma concentration, terminal elimination rate constant, and area under the curve for norverapamil were similar in patients with renal failure and normal subjects. The study showed that the plasma disposition of verapamil and norverapamil was not affected in patients with impaired renal function. Furthermore, this study does not indicate that any change in dosage is necessary when single doses of verapamil are administered to patients with renal failure.
Orthostatic hypotension has a number of causes, many of which are easily reversible. However, characteristics such as standing hypotension in conjunction with supine hypertension are not always easily detected in the clinic or office setting. Ambulatory blood pressure monitoring may be a valuable technique for diagnosis and for the assessment of therapeutic effects in patients with orthostatic hypotension.
Advancing technology will develop lighter, less expensive, more compatible, and more reliable ambulatory blood pressure recording devices, which will result in an increased use of the procedure in clinical practice. Future longitudinal prospective studies of normotensive and hypertensive subjects may authenticate the relationship between ambulatory blood pressure values and cardiovascular morbidity and mortality, thus enabling clinicians to generate guidelines for the diagnosis and treatment of hypertension. Until that happens, ambulatory blood pressure monitoring can provide meaningful supplemental information that overcomes the limitations of office blood pressure. In addition, various cardiovascular disorders may only be evaluated by using ambulatory blood pressure monitoring. Finally, ambulatory blood pressure monitoring is valuable in determining the efficacy of antihypertensive medications and improving the research trials of these drugs.
In the past, the diagnosis and management of hypertension has been based on office blood pressure. However, office blood pressure is not always a true reflection of a patient's blood pressure profile. Since ambulatory blood pressure monitoring permits a large number of readings to be taken in the patient's usual environment, it may provide a more representative blood pressure profile. Indeed, ambulatory blood pressure has been better correlated than office blood pressure with the target-organ complications of hypertension. Office or white-coat hypertension (elevated blood pressure only when measured in the physician's office) has been reported in 12-21% of patients in mildly hypertensive sample populations. While office blood pressure and daytime ambulatory blood pressure values are reported to be similar in normotensive subjects, ambulatory systolic and diastolic readings in hypertensive subjects have been reported as, respectively, 4-15 mmHg and 3-10 mmHg lower than office blood pressure readings. In estimating a patient's mean blood pressure and diagnosing hypertension, the greater the number of recording hours the more accurate the estimate is likely to be; in addition, increasing the number of measurements per hour also improves accuracy and increases the sensitivity of the readings. An increased frequency and severity of target-organ damage has been associated with higher 24-h blood pressure variability. Although the diagnosis of hypertension should not be based on ambulatory blood pressure alone, there are many clinical problems for which ambulatory blood pressure can be useful.
The blood pressure response to a new sustained-release formulation of nifedipine was evaluated in an 8-week, double-blind, placebo-controlled study. Twenty-nine patients with mild essential hypertension were randomized to receive placebo (N = 9), 30 mg nifedipine (N = 10), or 60 mg nifedipine (N = 10). During treatment, 30-mg and 60-mg doses of nifedipine administered once daily decreased office blood pressures from 137/98 +/- 8/2 mm Hg and 141/98 +/- 15/2 mm Hg at baseline, respectively, to 126/89 +/- 9/7 mm Hg and 126/86 +/- 6/7 mm Hg (P less than .005). Noninvasive automatic ambulatory blood pressure monitoring demonstrated a marginally significant (P less than .10) reduction in the mean 24-hour blood pressure of 2/6 +/- 8/8 mm Hg and 5/6 +/- 9/9 mm Hg for patients taking 30 mg and 60 mg nifedipine once daily, respectively. Diastolic blood pressure load (the percentage of ambulatory diastolic blood pressure readings greater than 90 mm Hg) during 24 hours was decreased by 41% and 35%, with 30 mg and 60 mg nifedipine administered once daily, respectively. No significant dose response to nifedipine at these dose levels was observed. Although the once-daily formulation of nifedipine achieved effective control of office blood pressure, similar control was not observed in awake and 24-hour periods in all patients.
The variability of casual (office) blood pressure according to position at the time of measurement was investigated in 168 untreated patients with a history of mild to moderate essential hypertension. Two measurements were made in the supine, sitting, and standing positions on each of 2 consecutive days, and 24-hour ambulatory blood pressure monitoring was performed. The mean supine, sitting, and standing blood pressures were 146 +/- 15/91 +/- 7, 144 +/- 15/96 +/- 8, and 149 +/- 17/103 +/- 7 mm Hg, respectively. Diastolic blood pressures were significantly different from each other (P less than 0.0001). Supine and sitting systolic blood pressures were not different, but they were different from standing blood pressure (P less than 0.0001). The mean of all three positions (overall blood pressure) was 146 +/- 15/96 +/- 7 mm Hg. Supine, sitting, standing, and overall diastolic blood pressure means were 90 mm Hg or more in 88, 133, 164, and 133 patients, respectively. The mean awake ambulatory and 24-hour ambulatory blood pressures were 143 +/- 16/95 +/- 7 and 138 +/- 16/92 +/- 8 mm Hg, respectively, and diastolic blood pressures were 90 mm Hg or more in 121 and 88 patients, respectively. The correlation of office blood pressure with ambulatory blood pressure varied according to office position and was 0.76 to 0.82 (P less than 0.0001) for systolic blood pressure and 0.60 to 0.69 (P less than 0.0001) for diastolic blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
The kidneys of five hypertensive dogs with experimental unilateral renal artery stenosis were examined by 99mTc-diethylenetriaminepentaacetic acid (DTPA) and 131I-hippuran radionuclide dynamic scintigraphy at 10 and 40 min (respectively) following the administration of intravenous bolus injections of captopril. Doses of 0.2, 0.5, and 1.0 mg/kg captopril reduced mean arterial pressure by 33 +/- 4, 31 +/- 7, and 51 +/- 4 mm Hg and increased plasma renin activity by 40.1 +/- 9.8, 57.6 +/- 3.2, and 34.4 +/- 15.2 ng A1/mL/h, respectively. The time-activity curves of both 99mTc-DTPA and 131I-hippuran indicated that renal excretory function in the stenotic kidney was compromised with all three doses of captopril. However, if nitroprusside was used to reduce the mean arterial pressure to a level comparable to that with captopril, there was no appreciable increase in plasma renin activity and renal excretory function was only partially affected in the stenotic kidney. One hour after the administration of 0.5 mg/kg captopril, the function of the stenotic kidneys was partially restored and, by two hours, the time-activity curves were comparable to control scans. These data demonstrate a reversible, time-limited suppression of stenotic kidney function by captopril in renovascular hypertension and provide support for the use of captopril in the diagnosis of renovascular hypertension by radionuclide dynamic scintigraphy.
Twenty-two hypertensive patients were monitored during two separate drug-free occasions with a Del Mar Avionics ambulatory device. Blood pressure loads (percentage of systolic and diastolic readings more than 140 and 90 mmHg, respectively) and mean BP were measured both to determine their reproducibility and to examine how they correlate with each other. The systolic and diastolic mean awake BPs for day 1 and day 2 were 140/93 mmHg and 140/91 mmHg, respectively, and BP loads were 45%/55% and 43%/54%. Moreover, mean BP loads correlated highly (r = 0.93) with mean BP values taken on the same day. Both ambulatory mean SBP and BP load were highly reproducible (r = 0.87 and 0.80, respectively, during the awake hours), and mean DBP and load were fairly reproducible (r = 0.59 and 0.39, respectively, during the awake hours). Clinically, however, both were consistent from day 1 to day 2. Mean and individual standard deviations also were reproducible for both systolic and diastolic pressures and loads.
To serve as a tentative reference group for clinical health, 107 adults measured their systolic (S) and diastolic (D) blood pressure (BP) with an ambulatory Del Mar Avionics monitor (Irvine, California). Data were collected over approximately 24 hours at 7.5-minute intervals during waking and at 15-minute intervals during sleep. An echocardiogram served to determine the left ventricular mass (LVM), septal wall thickness (SWT), posterior wall thickness (PWT), ejection fraction (EjFr), and left atrial size (LAS). Each data series was analyzed by single cosinor. A statistically significant circadian rhythm (P less than 0.05) was found in 96 subjects (89.7 percent) for SBP and in 86 subjects (80.4 percent) for DBP. A population-mean cosinor reveals a highly significant circadian rhythm (P less than 0.001) for both variables in men (n = 44) as well as in women (n = 63), with an acrophase around 14:15. The double circadian amplitude, a measure of the total predictable change within a day, averages 10 (women) and 11 (men) mm Hg for DBP and 14 (women) and 17 (men) mm Hg for SBP. The midline-estimating statistic of rhythm (MESOR) of SBP is found to be higher for men (125 mm Hg) than for women (120 mm Hg), P = 0.018, whereas no difference in MESOR is found for DBP (71 mm Hg). A statistically significant correlation with age is found for the MESOR of SBP in both men (r = 0.352; P = 0.018) and women (r = 0.336; P = 0.007). The MESOR of SBP is also found to correlate with LVM in men (r = 0.300; P = 0.046), but not in women (r = 0.181; P = 0.153), whereas the MESOR of DBP correlates with LVM in women (R = 0.316; P = 0.011) but not in men (r = 0.117; P = 0.543). A positive correlation is also found between the MESOR of SBP and SWT as well as with EjFr, which is more prominent in women; between the MESOR of DBP and LAS, which is more prominent in men; and a negative correlation is found for women but not men between the circadian amplitude of both SBP and DBP and EjFr. Blood pressure excess (in mm Hg x h; hyperbaric index, briefly HBI; Halberg et al., 1984) was computed by comparing each profile to the upper 95 percent time-varying prediction limit of healthy peers.(ABSTRACT TRUNCATED AT 400 WORDS)