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Biomedical subjects

A C Tan

Publications and source records attributed to A C Tan.

At least 37 records · Page 2Linked to original sources

Comparison of cyclic guanosine monophosphate response to infusion of atrial natriuretic peptide in young and elderly subjects.

OBJECTIVE: To compare the sensitivity to atrial natriuretic peptide (ANP) in young and elderly subjects. DESIGN: Double-blind, random-order, placebo-controlled study using two different rates of ANP infusion. SUBJECTS: Eight healthy young (23 +/- 3 years, mean +/- SD) and eight healthy elderly (76 +/- 4 years) subjects recruited from the general population. MEASUREMENT: Plasma cyclic guanosine monophosphate (cGMP, the second messenger of ANP) levels reflecting the sensitivity of biologically active ANP receptors. RESULTS: Baseline ANP levels were higher and rose to a greater extent in the elderly both during low- (0.25 microgram/min) and high-dose (2.0 micrograms/min) infusion of ANP. Plasma levels of cGMP rose in proportion to the increase in ANP. When the rise in cGMP levels was related to the increase in ANP levels (expressed as nmol/L per 100 pg/mL ANP increase), no difference was found between young and elderly subjects. CONCLUSION: The ability of elderly subjects to increase cGMP in response to exogenous ANP is similar to that of young subjects. This may reflect a similar sensitivity of the target organs towards ANP. However, because of lower clearance in the elderly, a similar dose of ANP results in a greater elevation of ANP and cGMP levels and hence induces a greater effect.

Adult↗

Atrial natriuretic peptide. An overview of clinical pharmacology and pharmacokinetics.

The atrial natriuretic peptide (ANP) is part of a new family of cardiac hormones regulating water and salt homeostasis. Besides acting as a blood pressure-lowering agent, it also exerts potent natriuretic and diuretic effects. ANP can be considered an endogenous antagonist of the reninangiotensin-aldosterone system and the antidiuretic hormone. One of the roles of ANP is to protect the body against fluid overload: it decreases intravascular fluid volume, which in turn diminishes cardiac secretion of ANP. The pharmacokinetic parameters of ANP reported in the literature vary widely. In general, ANP rapidly disappears from plasma with a high total body clearance. This is in agreement with the short-lived effects of the hormone. The actions of ANP have led to efforts to use this peptide hormone in the treatment of various cardiovascular disorders such as hypertension and congestive heart failure. Intravenous ANP administration indeed resulted in beneficial effects in these disorders. However, the peptide nature of ANP and its rapid elimination from the circulation limit its suitability as a drug. More promising is the development of long-acting ANP analogues and inhibitors of ANP degradation. Proper understanding of ANP pharmacokinetics is essential for the clinical use of these pharmacological agents.

Animals↗

Three-dimensional visualization of data on human anatomy: diagnosis and surgical planning.

A system is described which produces displays of anatomical surfaces from sets of X-ray computed tomography (CT), magnetic resonance imaging (MRI) and ultrasonographic scans (US). The displays are created to show the three-dimensional character of the internal and external anatomy. The images may be manipulated on the screen to simulate dissection of the three-dimensional object they represent. Thus it is possible to increase the diagnostic value of the original data and to plan surgery by simulation. To allow long-term studies on the human face for surgical planning and assessment a non-hazardous optical scanning system has been devised. The display system also produces data to drive a numerically controlled milling machine for the production of models, prostheses and implants.

Anthropometry↗

Kinetics of atrial natriuretic peptide in young and elderly subjects.

To study the influence of age on the kinetics of atrial natriuretic peptide (ANP) in man, human (99-126) ANP 2.0 micrograms.min-1 was infused IV for 60 min in 8 healthy young (18 to 25 y) and 9 healthy elderly (71 to 84 y) subjects. Both baseline ANP values and the levels at the end of infusion were higher in the elderly subjects. The mean residence time of ANP in the two age groups was not significantly different, whereas total body clearance (CL) was markedly diminished in the elderly as compared to the young subjects (mean +/- SD 3.1 +/- 1.0 l.min-1 and 6.2 +/- 4.1 l.min-1, respectively). The apparent volume of distribution at steady state was lower in the elderly than in the young, but the difference was not significant (mean +/- SD 44 +/- 19 and 103 +/- 111, respectively. The decrease in CL largely explained the higher ANP levels found in the elderly subjects. The MRT and the plasma half-life of the terminal phase did not differ between the two groups. In the elderly but not in the young subjects the calculated endogenous creatinine clearance was closely correlated with the CL (r = 0.90, P less than 0.001), thereby emphasizing the importance of the kidney in the metabolic clearance of ANP in the elderly.

Adolescent↗

Mild dehydration and atrial natriuretic peptide in young and elderly subjects.

The influence of mild dehydration on plasma levels of atrial natriuretic peptide (ANP) was studied in both young (aged 18 to 25 years) and elderly (aged 72 to 86 years) subjects. We expected that dehydration would lower ANP concentrations due to the ensuing volume contraction. A different response of the ANP hormonal system in the elderly might help to explain the observation that elderly subjects are more predisposed to dehydration as compared to young subjects. Dehydration was induced by restriction of fluid intake to 25% of normal for one day. During the study, urinary osmolality increased while osmolar clearance and body weight decreased. Basal ANP concentrations were higher in the elderly subjects. However, these levels did not change during the dehydration study neither in the young nor in the elderly subjects. This may be explained by the activation of counter-regulatory systems preventing a decrease in central blood volume and hence a decrease in ANP concentration.

Adolescent↗

Age-dependent vasodilation of the skin microcirculation by atrial natriuretic factor.

The microcirculatory responses to systemically administered alpha-human atrial natriuretic factor [99-126)hANF) (ANF) were investigated in the skin of eight young (18-25 years) and eight elderly (71-84 years) healthy volunteers in a double-blind, randomized, placebo-controlled study. Laser-Doppler flux (LDF), transcutaneous oxygen pressure (TcPO2), and skin temperatures on the finger (Td) and on the cheek (Tc) were measured during 60 min of i.v. ANF administration at a low rate (0.25 micrograms/min), resulting in plasma ANF concentrations in the upper normal range, and at a high rate (2.0 micrograms/min), inducing a 17- to 23-fold increase in plasma ANF. ANF infusion did not induce consistent changes in TcPO2 or Td at either rate. Placebo-corrected LDF increased significantly following low-rate ANF infusion in the elderly but remained unchanged in the young (mean +/- SD) +22 +/- 21% (p less than 0.05) and +7 +/- 32% (p greater than 0.1), respectively; following high-rate ANF infusion in LDF the changes were greater, with +28 +/- 56% and +19 +/- 42%, respectively. Because of the large SD the increases were no longer significant. During high-rate ANF infusion Tc remained unchanged in the young, but in the elderly Tc decreased--1.1 +/- 1.3% (p less than 0.05), which is probably due to the fall in blood pressure, which was more pronounced in the elderly than in the young: mean arterial blood pressure (MAP) decreased -9 +/- 3% (p less than 0.05) in the elderly and just -6 +/- 3% (p less than 0.05) in the young, both corrected for placebo changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Attenuated forearm vasodilator response to atrial natriuretic factor in the elderly.

The vasodilator potency of human atrial natriuretic factor-(99-126) was investigated in the forearm vascular bed of 10 young and 10 elderly normotensive volunteers with venous occlusion strain gauge plethysmography. Atrial natriuretic factor was infused at six increasing dose steps into the brachial artery from 0.001 up to 0.3 microgram/min/100 ml of forearm volume. This induced a mean +/- SEM increase in blood flow from 1.4 +/- 0.2 up to 6.0 +/- 1.0 ml/min/100 ml in the young and from 1.4 +/- 0.2 up to 3.9 +/- 0.6 ml/min/100 ml in the elderly. The dose-response curves of forearm blood flow and of forearm vascular resistance after increasing infusion rates of atrial natriuretic factor were shifted to the right in the elderly when compared with the young subjects. The mean percent decrease in forearm vascular resistance, induced by atrial natriuretic factor, during this dose-response curve averaged -31 +/- 3% in the elderly versus -56 +/- 3% in the young subjects (p = 0.0002). The calculated forearm spillover of the second messenger of atrial natriuretic factor, cyclic guanosine monophosphate, significantly increased from baseline values of 1.2 +/- 1.1 and 0.7 +/- 0.5 pmol/min/100 ml in young and elderly subjects, respectively, up to 23.2 +/- 5.0 and 30.5 +/- 7.0 pmol/min/100 ml during the highest dose of atrial natriuretic factor (both p less than 0.01 versus baseline). There were no significant differences in the increments of the forearm spillover of this second messenger between both age groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

ANP after AMI.

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Atrial Natriuretic Factor↗

Hemodynamic effects of atrial natriuretic factor in young and elderly subjects.

Because levels of plasma atrial natriuretic factor (ANF) increase with advancing age, a diminished hemodynamic responsiveness to ANF in the elderly has been hypothesized in the literature. Therefore hemodynamic effects after two infusion rates (0.25 and 2.0 micrograms/min) of atrial natriuretic factor (99-126) were investigated in young (n = 8) and elderly (n = 9) volunteers in a double-blind, randomized, and placebo-controlled protocol. After low-rate infusion, ANF concentrations increased to the upper normal range, and only minor effects were observed. In contrast, high-rate infusion resulted in a decrease in blood pressure and forearm vascular resistance, whereas an increase in heart rate was observed in both groups. Between young and elderly subjects, a significant difference was observed in the ANF-induced decrease in systolic blood pressure (mean +/- SD, -4% +/- 4% versus -12% +/- 7%, p less than 0.05) and mean arterial pressure (-6% +/- 5% versus -11% +/- 4%, p less than 0.05) during the high rate infusion. When compared with the concentrations of the young subjects, the ANF concentrations reached at both ANF dosages were higher in the elderly subjects; this was the result of a diminished ANF clearance in the elderly subjects. After correction of the changes of systolic blood pressure and mean arterial pressure for the higher ANF levels reached within this elderly group, no difference between young and elderly subjects remained. We conclude that a diminished cardiovascular responsiveness to ANF with advancing age could not be demonstrated. In contrast, the high-rate infusion of ANF induced an increased hemodynamic response in the elderly subjects, but this seems to be the result of the higher ANF levels reached within this group.

Adult↗

The effect of volume expansion on atrial natriuretic peptide and cyclic guanosine monophosphate levels in young and aged subjects.

The relationship between atrial natriuretic peptide (ANP) and age was studied. In elderly subjects (65 to 84 years) higher basal ANP levels were found as compared with those found in young subjects (21 to 23 years). Volume loading (750 mL 0.9% NaCl in 60 minutes) increased ANP levels only in the aged group, and plasma renin activity decreased only in the young subjects. Plasma aldosterone levels did not change. Basal cyclic guanosine monophosphate values did not differ in either group, and rose to a similar extent during volume loading. High pressure liquid chromatography analysis did not suggest different molecular forms of immunoreactive ANP in elderly subjects. The main circulating component both basal and after stimulation corresponds to the (99-126)hANP form.

Adult↗

Effects of dietary sodium restriction and posture on plasma levels of atrial natriuretic peptide, aldosterone and free aldosterone in normal human pregnancy.

The effects of dietary sodium restriction and posture on plasma concentrations of atrial natriuretic peptide (ANP), aldosterone and free aldosterone were investigated in ten women between weeks 29 and 33 of normal pregnancy. Hormone levels were studied during unrestricted sodium intake and on day 6 of a low sodium diet. On both occasions venous blood was obtained in the sitting as well as in the left lateral tilt position. Plasma concentrations of ANP during the unrestricted sodium intake were not raised compared with control values in healthy non-pregnant females. Recovery experiments showed no differences in the degradation of ANP in blood from pregnant and non-pregnant women. Plasma concentrations of ANP significantly decreased (by 32%) in response to the low sodium regime in both positions. Concentrations of aldosterone and free aldosterone (in women in the sitting position) increased twofold after sodium restriction. Mean values of ANP were higher in women in the left lateral tilt position that in those in the sitting position, but the difference was not significant. Concentrations of aldosterone and free aldosterone were significantly lower (by around 30%) in women in the left lateral tilt position compared with those in the sitting posture.

Adult↗

Evaluation of a direct assay for atrial natriuretic peptide.

A direct radioimmunoassay for the assessment of human atrial natriuretic peptide (ANP) in plasma, using a highly specific antibody and a well-defined monoiodotyrosyl-tracer was developed and evaluated by concurrent application of an extraction method. Sensitivity was 13.4 pg/ml; intra- and interassay variations were 3.1 and 5.5%, respectively; recovery averaged 99%; normal values ranged from 15-111 pg/ml (mean +/- SD = 59 +/- 25 pg/ml, n = 41). The results, including the effect of exercise, of the two methods correlated well. Pooling ANP values in normal subjects and patients with congestive heart failure gave a good correlation (p less than 0.01). However, due to processes in unextracted plasma, in the lower range the results from the direct method were erratic. Velocity and duration of centrifugation changed the number of platelets, but no effect on ANP levels, whether assessed by the direct or by the extraction method, was observed. Although the direct method is considerably less laborious than the extracted method its lack of reliability disqualifies it for most purposes.

Adult↗

Atrial natriuretic peptide after myocardial infarction.

Plasma concentrations of atrial natriuretic peptide (ANP) after acute myocardial infarction were measured at fixed times during 48 hours in 38 patients admitted to the hospital within 4.4 hours after the onset of symptoms. Three hours after admission, the mean concentration of ANP was significantly lower than that at the time of admission. Thereafter it rose steadily until 15 hours after admission. ANP concentrations measured in each patient at the time of admission and the individual mean ANP concentrations during the first 48 hours after admission correlated weakly but significantly with the size of the infarct and the left ventricular function. Neither the site of the infarct, the occurrence of reperfusion, nor the number of coronary vessels affected influenced the ANP concentration. In 24 patients in whom cardiac catheterization was performed, no relationship between ANP concentrations and left ventricular pressures was observed. Determination of ANP concentrations seems to be of little value in assessing cardiac function after acute myocardial infarction.

Adult↗

ANP in AMI.

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Atrial Natriuretic Factor↗

Application of 3-D computer graphics for facial reconstruction and comparison with sculpting techniques.

Facial reconstruction has until now been carried out by the sculpting technique. This method involves building a face with clay or other suitable material on to a skull or its cast, taking into account appropriate facial thickness measurements together with information provided by anthropologists such as approximate age, sex, race and other individual idiosyncrasies. A method for facial reconstruction is presented using 3-D computer graphics and is compared with the manual technique. The computer method involves initially digitising a skull using a laser scanner and video camera interfaced to a computer. A face, from a data bank which has previously digitised facial surfaces, is then placed over the skull in the form of a mask and the skin thickness is altered to conform with the underlying skull. The advantage of the computer method is its speed and flexibility. We have shown that the computer method for reconstructing a face is feasible and furthermore has the advantage over the manual technique of speed and flexibility. Nevertheless, the technique is far from perfect. Further facial thickness data needs collecting and the method requires evaluation using both known control skulls and later unknown remains.

Computer Graphics↗