Showing papers in "Clinical Science in 1986"

Chemiluminescence immunoassay: an overview.

Abstract: A large number of techniques cxist though some arc more suitable than others for the measurement of a particular compound, considerations being given to its size and its concentration. Howcver, all immunoassays require two components, firstly an antibody capable of specifically binding the compound and, secondly, a tracer which permits this binding reaction to be observed. In classical radioimmunoassay (RIA) [ 11 the compound is allowed to react with an antibody, in competition with a radiolabelled antigen analogue for a limited number of antibody binding sites. T h e distribution of radiolabel between antibody bound and free fractions is a measure of the quantity of the compound present. The choice of radiolabel depends upon the compound analysed and may be internal or external. Small molecules usually employ internal labels, for example 3H in steroids and lZsI in thyroid hormones, whereas large molecules invariably utilize an external label, 12'I. Radioiodine has a sensitivity of detection approximately 1000fold that of tritium and is thus universally employed. However, in RIA systems sensitivity is not necessarily limited by the sensitivity of detection of the label but is ultimately dependent upon the equilibrium constant of the antibody-antigen

Human calcitonin gene related peptide: a potent endogenous vasodilator in man

Abstract: In addition to calcitonin and katacalcin, it is now known that the human calcitonin gene encodes a novel peptide called calcitonin gene related peptide (CGRP). In experimental animals, CGRP produces vasodilatation and complex changes in plasma calcium. We have now assessed its biological activity in man by infusing human CGRP (hCGRP) into six normal volunteers. hCGRP (545 pmol/min) caused the diastolic pressure to fall from 64 +/- 5 to 55 +/- 7 mmHg (P less than 0.05), the heart rate to increase from 61 +/- 7 to 87 +/- 5 beats/min (P less than 0.05) and the skin temperature to increase from 33.7 +/- 0.9 to 34.9 +/- 0.5 degrees C. Plasma noradrenaline increased from 481 +/- 126 to 835 +/- 65 pg/ml (P less than 0.05) and plasma adrenaline from 57 +/- 17 to 82 +/- 12 pg/ml (P less than 0.05). There were no significant changes in the albumin-corrected plasma calcium. hCGRP is thus a potent endogenous vasodilator in man and is in fact more potent than any other known vasodilator. Together with the observations that CGRP circulates in normal subjects at relatively high concentration (approximately 25 pmol/l) and that CGRP is present in perivascular nerves, this study suggests a possible role for CGRP in controlling peripheral vascular tone in man.

Lactulose 51Cr-labelled ethylenediaminetetra-acetate, l-rhamnose and polyethyleneglycol 500 as probe markers for assessment in vivo of human intestinal permeability

Abstract: The urinary excretion of lactulose, 51Cr-labelled ethylenediaminetetra-acetate (51Cr-EDTA), L-rhamnose and polyethyleneglycol 400 (PEG-400) has been measured after intravenous and oral administration in healthy volunteers. Intestinal permeation of the probes was compared after their ingestion in iso-osmolar, hyperosmolar and cetrimide-containing test solutions. Urinary recovery of lactulose and 51Cr-EDTA after intravenous administration reached 75% by 5 h, and exceeded 90% at 24 h, and these values were 62 and 72%, respectively, for L-rhamnose. Recovery of PEG-400, however, varied with the relative molecular mass (Mr) of each polymer from 25.9 to 68.5% in 24 h. Intestinal permeation of ingested lactulose and 51Cr-EDTA was low, but that of L-rhamnose was 45-fold, and that of PEG-400 100-fold, greater. Permeation of lactulose and 51Cr-EDTA was markedly increased by cetrimide and hyperosmolar stress, whereas that of L-rhamnose showed little change. PEG-400 permeation was not affected by cetrimide, but was slightly increased by hyperosmolar stress. The 5 h permeation of lactulose, but not of L-rhamnose or PEG-400, correlated with that of 51Cr-EDTA (r = 0.98, P less than 0.001). These findings are compatible with three distinct pathways of unmediated mucosal permeation, L-rhamnose (radius less than 0.4 nm) passing mainly through small aqueous 'pores' of high incidence, lactulose and 51Cr-EDTA (radius greater than 0.5 nm) through larger aqueous 'channels' of low incidence susceptible to cetrimide and hyperosmolar stress, and PEG-400, which has appreciable lipid solubility, by partition through cell membrane lipid as well as the aqueous 'pores'.

Brown adipose tissue uncoupling protein content in human infants, children and adults.

Abstract: 1 A solid-phase radioimmunoassay is described for the estimation of the uncoupling protein content of human brown adipose tissue mitochondria, as an index of thermogenic capacity 2 The concentration of inner mitochondrial membrane uncoupling protein was measured in brown adipose tissue samples from 48 individuals who died suddenly 3 The uncoupling protein content of axillary adipose tissue was greater than that of perirenal adipose tissue 4 Variations in brown adipose tissue uncoupling protein content, which would be consistent with changing thermogenic requirements and capacity, were observed in different groups of subjects Significantly lower concentrations were found in adults and in pre-term and stillborn infants than in older infants and children

The osmotic thresholds for thirst and vasopressin release are similar in healthy man

Abstract: The relationship between thirst perception and plasma osmolality was studied during hypertonic and physiological saline infusion in ten healthy volunteers. Thirst perception was quantified using a linear visual analogue scale which volunteers marked at intervals during the infusion periods. Infusion of hypertonic saline caused a steady rise in plasma osmolality together with a progressive linear increase in thirst perception and also plasma arginine vasopressin. No significant changes in thirst, plasma osmolality or plasma arginine vasopressin occurred during infusion of physiological saline. Linear regression analysis of the results defined the functions. Thirst (cm) = 0.3 (plasma osmolality-281) (r = +0.92, P less than 0.001) and plasma arginine vasopressin (pmol/l) = 0.4 (plasma osmolality-285) (r = +0.96, P less than 0.001). The osmolar threshold for thirst onset thus defined (281 mosmol/kg) was much lower than in previous studies and similar to the theoretical osmolar threshold for vasopressin release (285 mosmol/kg). We conclude that thirst perception rises in a progressive fashion throughout a wide range of plasma osmolality and that the osmolar threshold for thirst onset is similar to the theoretical osmolar threshold for vasopressin release. The results are compatible with the concept of either a single osmoreceptor subserving both thirst and vasopressin release, or two osmoreceptors sharing similar functional characteristics.

The plasma release of atrial natriuretic peptide in man.

Abstract: We studied plasma atrial natriuretic peptide (ANP) concentrations in seven normal subjects after the acute intravenous infusion of sodium chloride/potassium chloride solution (saline). Three separate infusions of 6, 12 and 18 ml of saline/kg body weight each significantly increased the circulating concentration of ANP without changes of plasma osmolality or electrolyte concentrations. The mean maximal rise of the plasma ANP concentration after the three saline infusions was significantly correlated (r = 0.74, P less than 0.001) with, but occurred 10-30 min later than, the maximal atrial pressure rise. These observations are in accord with the hypotheses that: (a) ANP is a circulating natriuretic factor; (b) atrial distension is an important stimulus to ANP release in man.

Muscle metabolism in patients with peripheral vascular disease investigated by 31P nuclear magnetic resonance spectroscopy.

Abstract: 1. Eleven men with claudication and ten control subjects had calf muscle metabolism studied at rest and during exercise and the subsequent recovery period by P nuclear magnetic resonance (n.m.r.) spectroscopy. 2. The muscle of patients with severe claudication had a significantly greater depletion of phosphocreatine and fall in pH during exercise and a slower recovery of phosphocreatine and pH after exercise. 3. The muscle of patients with both mild and severe disease had slower rates of ADP recovery after exercise than that of control subjects. 4. Surgical correction of the associated arterial stenosis abolished claudication and led to correction of the metabolic abnormalities in two patients. 5. Claudication pain was not related to intracellular pH or concentration of phosphorus-containing metabolites. 6. Energy production via oxidative metabolism is impaired but glycolysis may be increased in the calf muscle of patients with intermittent claudication.

Autonomic nervous control of the heart rate during dynamic exercise in normal man

Abstract: 1. The relative contribution of the efferent components of the sympathetic and parasympathetic nervous systems to the heart rate (HR) response to dynamic physical exercise was evaluated in 23 normal males. 2. The dynamic exercise was performed on a bicycle ergometer at work loads of 25, 50 and 100 W, before and after pharmacological blockade with atropine (13 individuals) or propranolol (10 individuals). 3. Parasympathetic blockade significantly depressed the rapid HR response at the beginning of the exercise period at all levels of intensity, whereas sympathetic blockade only affected the slow-response phase (1–4 min), especially at the highest level of effort. 4. The present results suggest that the tachycardia evoked by dynamic exercise is mediated by a biphasic mechanism initially depending on rapid vagal release, which increases progressively with increasing effort. An increased sympathetic activity manifests itself in a more delayed manner, especially at the higher levels of activity. 5. Continuous monitoring of HR during the entire period of activity at different levels of intensity permits the utilization of dynamic exercise as a simple and non-invasive method for the functional evaluation of the two components of the autonomic nervous system of the heart.

Hyperlipidaemia of diabetes

Abstract: There is general agreement as to the effects of diabetes on the concentrations of certain plasma lipoprotein lipids. Subdivision of diabetic subjects into several clearly defined subgroups has revealed that the detailed patterns of lipoprotein and lipid changes are dependent upon several factors, perhaps the most important of which is the degree of glycaemic control. Several aspects remain controversial, the most outstanding being whether or not plasma LDL cholesterol levels are elevated. It is possible that this is the case in certain clearly defined subgroups but not in others. In assembling the results of recent research for this review, two important aspects have emerged which require clarification. The first is the question of whether or not insulin directly stimulates hepatic VLDL secretion. The possibility that insulin might regulate production of lipogenic substrate by the gut may have an important bearing on this problem. The exact means by which insulin co-ordinates the metabolic activities of these organs in such a way as to ensure plasma lipid balance is not yet known and further research in this area may help to resolve some outstanding problems associated with diabetic hyperlipidaemia. Second, changes in the relative lipid composition of certain lipoprotein fractions in diabetic subjects has provided indirect evidence that increased lipoprotein 'remnant' concentrations may contribute to the abnormalities observed in some groups of diabetic subjects. This interesting possibility has been supported by metabolic studies, mainly in experimental animals. If this proves to be correct, then it remains to be determined whether the remnants involved are of hepatic or intestinal origin and whether the metabolic defect is related to abnormal production, clearance, or both. Recent work on the effects of changes in the apoprotein and lipid content on the metabolism of other lipoproteins in diabetes may have a useful bearing on studies of this type. In this respect, the bulk of the evidence seems to suggest that these factors, rather than changes in lipoprotein receptor activity per se, are important in determining the clearance of atherogenic lipoproteins such as LDL in diabetes.

Atrial natriuretic peptide inhibits the aldosterone response to angiotensin II in man

Abstract: We have investigated the interaction between the recently discovered natriuretic factor alpha human atrial natriuretic peptide (alpha h-ANP) and the renin-angiotensin-aldosterone system in man. Angiotensin II infused with placebo produced a significant rise of plasma aldosterone concentration (mean +/- SEM increment 352 +/- 23 pmol/l, n = 7, P less than 0.001). The infusion of alpha h-ANP together with angiotensin II largely abolished the aldosterone response (P less than 0.001). Diastolic blood pressure rose in response to the infusion of angiotensin II with placebo (mean increment 21.0 +/- 0.9 mmHg, P less than 0.001). Systolic blood pressure increased to a lesser degree (mean increment 12.5 +/- 0.7 mmHg, P less than 0.001). The infusion of alpha h-ANP together with angiotensin II significantly blunted the diastolic pressor response (P less than 0.01). This ability of alpha h-ANP to blunt the pressor effect of angiotensin II may be important in the control of systemic blood pressure. The inhibition of angiotensin II-stimulated aldosterone release demonstrates that alpha h-ANP may not only be a circulating natriuretic factor in its own right but that it may also act as a modulator of a related endocrine system.

Effect of peptide chain length on amino acid and nitrogen absorption from two lactalbumin hydrolysates in the normal human jejunum.

Abstract: A double lumen jejunal perfusion technique has been used in man to study the effect of peptide chain length on absorption of amino acid nitrogen from two partial enzymic hydrolysates of lactalbumin. Copper-chelation chromatography showed that one lactalbumin hydrolysate (LH2) contained 98% peptides with a chain length greater than 4, whilst the other (LH1) contained a more even spread of chain lengths with 55% less than 4. Absorption of total nitrogen and of 14 amino acid residues occurred to a significantly greater extent from the low molecular weight LH1 than from the higher molecular weight LH2. The results suggest that the pattern of nitrogen and amino acid absorption from partial enzymic hydrolysates of whole protein is markedly influenced by peptide chain length and that brush border peptide hydrolysis has an important rate limiting effect on absorption rates.

Stereophotogrammetry for measuring rates of cutaneous healing: a comparison with conventional techniques.

Abstract: A portable stereocamera linked to a computer has been developed capable of taking photographs in the clinical situation. The accuracy and precision of this system has been measured and compared with direct tracing and simple photography, the two systems currently in use for this type of work. It was found to have a precision of better than 2% and to be accurate to within 1% for edge length and area in models of chronic leg ulcers whose dimensions were known exactly. These results are between five and ten times better than direct tracing and simple photography measured under similar circumstances. When used on patients' ulcers, stereophotogrammetry was found to have a precision of 2% for edge length and 3.4% for area, again between five and ten times more accurate than the other two systems. The accuracy with which an epithelial edge can be identified with the naked eye, a possible limiting factor in any visual measuring system, was measured on fixed preparations of healing wounds on pigs. The mean error was found to be 240 micron with a confidence limit of 440 micron. Finally, the rate of healing of chronic leg ulcers was measured in a clinical trial on patients. Only stereophotogrammetry had errors consistently smaller than the changes being measured in the clinical trial, making it the only system which can validly be used to study rates of healing in this model. It is also able to measure volume to within 5% and is unique in being able to do this noninvasively.

Atrial natriuretic peptide: physiological release associated with natriuresis during water immersion in man

Abstract: Thermoneutral water immersion produces a physiological increase of thoracic blood volume, raises central venous pressure and increases urinary sodium excretion by a hitherto ill-understood mechanism. We have investigated whether this enhanced sodium excretion could be mediated by the recently discovered natriuretic factor, atrial natriuretic peptide (ANP). During water immersion there was a highly significant (P less than 0.001) twofold increase of the mean plasma ANP concentration and a doubling of the mean urinary sodium excretion. Both were unchanged during the control experiments. These results are consistent with the hypotheses that ANP is released into plasma in response to central blood volume expansion and that it functions as a natriuretic hormone in normal man under physiological conditions.

Cardiovascular and metabolic responses to low dose adrenaline infusion: an invasive study in humans.

Abstract: Cardiovascular and metabolic responses to intravenous infusions of adrenaline (ADR), which raised arterial plasma ADR in a stepwise fashion from 0.3 to 1.3, 2.3 and 6.0 nmol/l, were studied in 11 healthy volunteers. ADR evoked marked and concentration-dependent increases in stroke volume and cardiac output (thermodilution), as well as decreases in the vascular resistances of the systemic circulation, calf and adipose tissue. These changes were significant from 1.3 nmol/l ADR. Less marked effects were found on blood pressure and heart rate. Significant arterial ADR concentration-effect relationships were found for cyclic AMP, glycerol, glucose, lactate and noradrenaline, but not for insulin. Cyclic AMP and glycerol were significantly elevated at 1.3, glucose at 2.3, but lactate not below 6.0 nmol/l ADR. Increases in adipose tissue blood flow and arterial glycerol levels were correlated (P less than 0.001), suggesting a metabolic component in the blood flow response of adipose tissue. Invasive haemodynamic measurements revealed that ADR at arterial concentrations within the lower physiological range had considerable effects on cardiac output and vascular resistances, despite moderate changes in the conventional non-invasive haemodynamic variables blood pressure and heart rate. ADR elicited clear-cut responses at arterial plasma concentrations attained during various kinds of mild to moderate stress.

The reproducibility of limb blood flow measurements in human volunteers at rest and after exercise by using mercury-in-Silastic strain gauge plethysmography under standardized conditions

Abstract: 1. A study to assess the reproducibility of limb blood flow measurements by venous occlusion plethysmography using mercury-in-Silastic strain gauges was performed in six normal volunteers under standardized conditions. 2. Using this technique forearm and calf blood flow were measured at rest and between 2 and 3 min after submaximal exercise on six separate occasions over a 1 month period. 3. The mean coefficient of variation for resting forearm blood flow was 10.5% (range 7.8-15.6%). 4. The mean coefficient of variation for resting calf blood flow was 11.5% (range 7.4-14.2%). 5. The mean coefficient of variation for post-exercise calf blood flow was 13% (range 11.5-16.4%). 6. The results suggest that limb blood flow measurement by this technique may be useful in studies where serial measurements are required.

Enhanced rectal potassium secretion in chronic renal insufficiency: Evidence for large intestinal potassium adaptation in man

Abstract: The role of the large intestine in K+ excretion in chronic renal insufficiency was studied with a rectal dialysis technique in 14 normal subjects and eight normokalaemic, normotensive patients with chronic renal insufficiency. At initial intraluminal K+ concentrations of 10, 20, 30 and 45 mmol/l, net K+ secretion in patients with renal insufficiency was significantly greater than in normal subjects by approximately 1.8 mumol h-1 cm-2. The increase in net K+ secretion was more marked in those patients with creatinine clearances of less than 10 ml/min. In contrast, there were no significant differences in net Na+ and water transport, transmucosal potential difference and plasma aldosterone concentrations between the two groups. With an initial intraluminal K+ concentration of 30 mmol/l, the addition of amiloride (final concentration 1 mmol/l) to the rectal lumen decreased net Na+ absorption and transmucosal potential difference in normal subjects by 69% (P less than 0.005) and 31% (P less than 0.005) respectively, and in patients with renal insufficiency by 75% (P less than 0.05) and 36% (P less than 0.05) respectively, but there was no change in net K+ secretion in either group. These results indicate that the K+ secretory capacity of the rectal mucosa increases in chronic renal insufficiency, and the large intestine may therefore contribute to the maintenance of K+ homoeostasis as renal K+ excretion declines. Increased rectal K+ secretion in renal insufficiency occurs independently of changes in plasma K+ and aldosterone concentrations, net Na+ absorption and transmucosal potential difference, and may reflect stimulation of an active K+ secretory process.

Change in plasma immunoreactive atrial natriuretic peptide during sequential ultrafiltration and haemodialysis.

Abstract: Plasma immunoreactive human atrial natriuretic peptide (Ir-ANP) levels were measured in eight patients with chronic renal failure who were volume-expanded and during treatment by sequential ultrafiltration and haemodialysis. One patient was studied at two separate treatment sessions. Plasma Ir-ANP levels were raised in all patients (mean +/- SE 184 +/- 44 pmol/l, n = 9) compared with healthy controls (11 +/- 1.4 pmol/l), but showed considerable inter-patient variability. Plasma Ir-ANP levels fell with fluid removal during ultrafiltration (123 +/- 30 pmol/l, n = 9, P less than 0.02) and again as fluid was removed during haemodialysis (76 +/- 20 pmol/l, n = 9, P less than 0.02). Seven patients studied 48 h later, before their next dialysis treatment, had regained weight and showed a coincident rise in circulating plasma Ir-ANP (130 +/- 33 pmol/l, n = 7). Our data would support the hypothesis that the secretion of ANP is determined by volume or by a stimulus related to volume. However, it does not exclude the possibility that a factor other than extracellular fluid volume expansion contributes to the raised plasma Ir-ANP levels in chronic renal failure.

Blood pressure in the puerperium.

Abstract: Blood pressure was measured by random zero sphygmomanometer in the morning and afternoon for 5 days after normal delivery in a group of 136 previously normotensive women. The number of women studied each day varied from 32 to 125. The afternoon blood pressure was higher than the morning blood pressure (differences: 1.7 mmHg systolic, 2.6 mmHg diastolic; P less than 0.05). Both systolic and diastolic blood pressures rose for the first 4 days after delivery. The average rise over the whole period was about 6 mmHg systolic and 4 mmHg diastolic (P less than 0.05). A considerable number of previously normotensive women displayed elevations of blood pressure in the puerperium. Twelve per cent of all patients exceeded a diastolic blood pressure of 100 mmHg.

Atrial natriuretic peptide: an endogenous factor enhancing sodium excretion in man.

Abstract: For many years experimental evidence has suggested the existence of a circulating factor able to enhance sodium excretion. Very recently peptides with natriuretic activity in experimental animals have been isolated from mammalian and human cardiac tissue. In order to determine whether this natriuretic activity has relevance to man we have studied the effects of an infusion of alpha-human atrial natriuretic peptide (alpha-h-ANP) in normal subjects. Sodium excretion trebled (P = less than 0.005) during the infusion of a calculated dose of 15 pmol of alpha-h-ANP min-1 kg-1 and there was an accompanying diuresis; radioimmunoassay of plasma alpha-h-ANP during the natriuresis indicated a mean peak incremental concentration of 203 +/- 78 (SEM) pmol/l. The infusion of a calculated dose of 1.5 pmol min-1 kg-1 did not affect sodium excretion. There were no haemodynamic changes and no side effects were noted.

Urogastrone-epidermal growth factor concentrations in prostatic fluid of normal individuals and patients with benign prostatic hypertrophy.

Abstract: High concentrations (272 +/- 33 ng/ml) of urogastrone-epidermal growth factor were measured in prostatic fluid from normal males by a specific radioimmunoassay. Significantly lower concentrations (155 +/- 24 ng/ml) were observed in the prostatic fluid of patients with benign prostatic hypertrophy than in the age-matched normal controls (2P less than 0.01). The growth factor content of seminal fluid was accounted for by the contribution of prostatic fluid. Immunochemical studies failed to show evidence of synthesis within the gland nor could high affinity receptors for the protein be demonstrated in membrane preparations of the gland.

Respiratory and cardiovascular effects of central and peripheral intravenous injections of capsaicin in man: Evidence for pulmonary chemosensitivity

Abstract: The respiratory and cardiovascular effects of capsaicin injection into the superior vena cava and an arm vein were studied in three normal subjects. No changes were seen in tidal volume, inspiratory time or expiratory time after capsaicin injection. Instantaneous heart rate, systolic blood pressure and diastolic blood pressure remained unchanged. Central and peripheral intravenous injections of capsaicin but not control solution above a threshold of 0.5 micrograms/kg produced dose-dependent sensations sequentially in the chest, face, rectum and extremities. The chest sensation, a 'raw, burning' feeling, occurred 3-4 s after central capsaicin injection. No subject reported feeling breathless. In one subject the maximum tolerable dose of capsaicin (4 micrograms/kg) produced paroxysmal coughing 3.9 s after a central injection. In two of the subjects capsaicin injection was repeated after inhalation of a 5% bupivacaine aerosol (aerodynamic mass median diameter 4.8 micron), sufficient to block the cough reflex to a 5% citric acid aerosol. Prior inhalation of local anaesthetic aerosol abolished the chest sensation after capsaicin injection; the other sensations were unaffected. This study demonstrates that stimulation of receptors accessible from the pulmonary vascular bed does not evoke the pulmonary chemoreflex in conscious man but can produce coughing. It provides evidence for the existence of a nociceptive system of nerve endings in the lung parenchyma that can be blocked by inhaled local anaesthetic aerosol.

The effects of alcohol on local, neural and humoral cardiovascular regulation

Abstract: Cardiovascular actions of alcohol have long been recognized [ 11 and extensively studied. However, the recent recognition of an association between alcohol consumption and hypertension [2] has led to a renewed interest in the effects of alcohol on cardiovascular regulation. This article reviews the acute and chronic effects of alcohol on the cardiovascular system and discusses possible mechanisms by which alcohol consumption may elevate blood pressure.

Impaired sodium excretion in response to volume expansion induced by water immersion in insulin-dependent diabetes mellitus

Abstract: The renal response to volume expansion produced by water immersion to the neck at 35 degrees C was examined in eight young normotensive uncomplicated insulin-dependent diabetic subjects and in eight matched normal control subjects. Both the diabetic and normal subjects manifested a renal response of natriuresis and kaliuresis on immersion, but the natriuretic response was reduced in the diabetic group. Thus the induced excretion of sodium over the 4 h of immersion was 40 +/- 5 mmol (mean +/- SEM) in the normal group compared with 22 +/- 4 mmol in the diabetic group (P less than 0.02). In the normal subjects creatinine clearance did not change during immersion compared with pre-immersion control values while in the diabetic group it rose from pre-immersion control values of 112 +/- 11 ml/min to a mean value of 127 +/- 11 ml/min during immersion (P less than 0.01). The diabetic subjects thus excreted less sodium despite an increased filtered load during water immersion. Fractional excretion of sodium was significantly reduced in the diabetic subjects compared with the normal control subjects (P less than 0.05). The suppression of plasma renin and aldosterone was similar in normal and diabetic groups. Tubular sodium retention could be an early functional change in the diabetic kidney, and be implicated in the development of diabetic nephropathy.

Effect of posture on plasma immunoreactive atrial natriuretic peptide concentrations in man

Abstract: The effect of changes of posture on plasma atrial natriuretic peptide concentrations and renal function was studied in normal human volunteers. Plasma atrial natriuretic peptide concentrations increased in the supine posture, reached a maximum value after 30-60 min, remained elevated for 4 h and decreased to baseline values on return to the upright posture. Inflation of antishock trousers, which apply positive pressure to the legs and lower abdomen, attenuated the fall in plasma atrial natriuretic peptide concentration in the upright position. In the supine posture there were increases in urine flow rate, sodium, lithium, fractional sodium and fractional lithium clearances. Fractional distal water and sodium excretion, and total distal water and sodium reabsorption, which were estimated by the lithium clearance technique, also increased. Heart rate and systolic and diastolic blood pressures decreased in the supine and increased on return to the upright posture. Inflation of antishock trousers prevented the increase in heart rate in the upright posture. The contribution of haemodynamic factors to the increase in plasma atrial natriuretic peptide concentrations in the supine position and the relationship between this increase and the associated changes in renal function are discussed. However, the contribution of atrial natriuretic peptide to these changes is uncertain.

Cardiac metabolism and performance during L-glutamic acid infusion in postoperative cardiac failure.

Abstract: 1. Intravenous infusion of l-glutamic acid results in the augmentation of the cardiac output and an improvement of the circulation in patients with postoperative cardiac failure. This effect is not accompanied by increased myocardial oxygen demand. 2. Arterial plasma glutamate level rises 10-fold and arterial-coronary sinus plasma glutamate difference increases fivefold during intravenous l-glutamic acid infusion. This leads to cessation of ammonia release from the myocardium, probably due to augmentation of glutamine synthesis and to an increase in alanine formation coupled with a change from lactate release to lactate uptake by the myocardium. 3. The data obtained suggest that the beneficial effect of l-glutamic acid on depressed cardiac function in postoperative patients is related to changes in myocardial metabolism. Glutamic acid may be useful in treatment of circulatory and metabolic disturbances in cardiac failure.

Chemical specificity of coughing in man

Abstract: 1. The purpose of this study was to test whether cough response to inhaled ultrasonically nebulized fluid is dependent on the ionic content of the fluid. 2. Coughing was recorded in human volunteers during inhalation of aqueous solutions in a series of double blind randomized experiments. 3. The occurrence of cough was found to be dependent on the concentration of chloride ions in the inhaled fluid, cough frequency progressively increasing as chloride ion concentration was reduced. 4. It is proposed that the ion composition of the surface lining fluid of the airway may moderate the cough response by means of a chemoreceptor, although tonicity may also be important.