bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma Noradrenaline Concentrations at Different Vascular Sites during Rest and Isometric and Dynamic Exercise
Authors: Watson R. D. S. , Page A. J. F. , Littler W. A. , Jones D. H. , Reid J. L.
Published: August 2015

1. Blood samples were obtained simultaneously from femoral artery and vein, pulmonary artery and antecubital vein at rest and during isometric and dynamic exercise in six patients during cardiac catheterization and plasma noradrenaline was measured radioenzymatically.

2. Analysis of variance indicated that differences between vascular sites were not significant, whereas differences between patients (P < 0·001) and differences between activities (P < 0·001) were significant.

3. Mean systemic arterial concentrations tended to be lower than pulmonary arterial concentrations during each activity, although the difference was not significant.

4. We conclude that forearm venous plasma noradrenaline concentrations are representative of those from other sites.
Anatomical Accuracy of Echocardiographically Assessed Left Ventricular Wall Thickness
Authors: Larkin H. , Johnson D. C. , Hunyor S. N. , Caspari P. , Kaplan R.
Published: August 2015

1. A comparison of direct measurement and M-mode echocardiography in the determination of posterior left ventricular wall thickness was performed in 26 subjects, of whom 21 underwent cardiac bypass surgery; the remainder came to necropsy.

2. In the surgical group a close correlation was demonstrated between direct measurement of posterior wall thickness and the echocardiographic end-diastolic dimension (r = 0·76, P < 0·001).

3. The necropsy measurement of posterior wall thickness correlated with the echocardiographic end-systolic dimension (r = 0·99, P < 0·001).

4. These findings confirm that the echocardiographic measurement of posterior wall thickness accurately reflects the anatomical dimension.
Renin Precursor Synthesis and Renin-Binding Proteins in the Mouse
Authors: Poulsen K.
Published: August 2015

1. The precursor synthesis of renin, the storage form in the kidney and the submaxillary gland, and the molecular nature of the forms in plasma were studied in the mouse.

2. Renin is synthesized as a precursor (pre-prorenin) with a molecular weight of 50 000.

3. Renin is stored in the submaxillary gland and the kidneys as fully active renin with a molecular weight of 40 000.

4. The predominant form of renin in plasma is the active mol. wt. 40 000 form. High-molecular-weight forms of renin (800 000 and 70 000) are also present in plasma.

5. Pure 125I-labelled mol. wt. 40 000 renin binds, after a change in the tertiary structure, to the plasma protease inhibitors α2-macroglobulin, inter-α-trypsin inhibitor and α2-antithrombin. It binds also to lipoprotein and an unidentified plasma protein. No binding was seen to more than 50 other studied plasma proteins.

6. The high-molecular-weight forms of renin in plasma may be complexes of renin with plasma protease inhibitors and lipoprotein.
Haemodynamic Effects of Captopril in Hypertensive Patients: Comparison with Saralasin
Authors: Fagard R. , Amery A. , Lijnen P. , Reybrouck T.
Published: August 2015

1. Captopril (25 mg) reduced plasma angiotensin II (ANG II) by 53% (P < 0·001) and mean brachial artery pressure (MBAP) by 18·7 mmHg (P < 0·001) within 75 min in 26 hypertensive patients. After 2 months (on 150–600 mg/day) MBAP had decreased by 27·1 mmHg (n = 18) with no further change of plasma ANG II. δMBAP was significantly related to control log plasma renin (PRA) and log ANG II in both conditions.

2. The acute depressor response to captopril was 11·2 mmHg greater (P < 0·001) than δMBAP during saralasin infusion (n = 12).

3. Heart rate slightly increased after acute administration of captopril (+ 3·3 beats/min; P < 0·005), but cardiac output was not significantly affected; systemic vascular resistance decreased by 10% (P < 0·01) with unchanged pulmonary vascular resistance.

4. During chronic administration, oxygen consumption, cardiac output and stroke volume increased by 15% (P < 0·01), with unchanged heart rate; systemic vascular resistance had dropped by 30% (P < 0·001).

5. Plasma ANG II and plasma aldosterone decreased, and PRA and ANG I increased acutely, with no further changes during chronic treatment.
Humoral Effects of the Oral Converting-Enzyme Inhibitor Sq 14 225 in Hypertensive Patients in Supine and Tilted Position
Authors: Morganti A. , Pickering T. G. , Lopez-Ovejero J. , Laragh J. H.
Published: August 2015

1. To evaluate the effects of converting-enzyme inhibition on the sympathetic nervous system, on renin and on the other known regulators of aldosterone secretion, we measured blood pressure, heart rate, plasma noradrenaline, adrenaline, renin activity, aldosterone, cortisol and serum potassium in 15 sodium-repleted hypertensive patients in supine position and during 30 min of 65° head-up tilt before and during treatment with SQ 14 225.

2. SQ 14 225 produced significant decreases in supine blood pressure and plasma aldosterone and significant increments in plasma renin activity and potassium; in contrast, heart rate, noradrenaline, adrenaline and cortisol were unchanged.

3. While in control tilt studies blood pressure was always maintained, during treatment three of 15 patients had vasovagal syncopes. In the remaining 12 blood pressure was maintained during tilt on SQ 14 225; however, while the tilt-induced responses in heart rate and adrenaline were as in control studies, the 30 min increments in noradrenaline were significantly higher.

4. Both before and during treatment the responses of plasma renin activity and aldosterone to tilt were parallel, and correlated with each other, and cortisol and potassium changed only slightly.

5. It is concluded that the SQ 14 225-induced fall in blood pressure occurs without a concomitant rise in sympathetic nervous activity; thus the increase in supine plasma renin activity, being a reflection of the interruption of the angiotensin feedback mechanism on renin release, indicates an effective suppression of angiotensin II formation.

6. During SQ 14 225 the persistence of aldosterone response to tilt and its relationship with renin activity suggest that the enzymatic blockade is over-ridden; however, in the presence of a reduced formation of angiotensin II a more pronounced response of the sympathetic nervous system is required to defend blood pressure against postural changes.
Catecholamines and Haemodynamics in Fixed Essential Hypertension
Authors: Agabiti-Rosei E. , Alicandri C. , Fariello R. , Muiesan G.
Published: August 2015

1. Arterial plasma catecholamines and haemodynamic status were simultaneously studied in 27 patients with fixed essential hypertension (WHO I—II).

2. Total arterial plasma catecholamines were found to be directly related to mean arterial pressure and to calculated total peripheral resistance, and they were inversely related to stroke index.

3. The degree of total peripheral resistance reduction after α-receptor blockade (phentolamine 10 mg intravenously) and the degree of mean arterial pressure reduction after combined α- and β-receptor blockade (labetalol 100 mg intravenously) were directly related to pretreatment plasma catecholamine concentrations.

4. These findings support the view that the sympathetic nervous system, as evaluated by plasma catecholamine concentration, may have an important role in maintaining hypertension in a subgroup of patients, contributing mainly to the degree of peripheral vasoconstriction.
Autoantibodies in Untreated and Treated Essential Hypertension: Relationship to Histocompatability Leucocyte Antigen-B15 and Vascular Complications
Authors: Kristensen B. Ø.
Published: August 2015

1. The presence of autoantibodies and the histocompatibility leucocyte antigen (HLA) antigen B15 was studied in relation to vascular complications (WHO III) in 148 patients with essential hypertension.

2. Nine of 36 patients with WHO stage III hypertension had autoantibodies, compared with seven out of 78 normotensive controls.

3. The frequency of B15 was 36·1% in hypertensive patients with stage III hypertension and 14·8% in controls. Nine of 18 patients with cerebral complications had B15 and four out of 18 with cardiac complications had B15.

4. The relative risk of vascular complications was 3·4 times higher in B15-positive patients with essential hypertension compared with B15-negative patients.

5. This study suggests that B15-positive patients with essential hypertension represent a subgroup with a higher risk of vascular complications. Long-term studies are needed to determine whether B15 might serve as predictor for vascular complications.

6. The study adds further support to suggestions of a genetic and possibly HLA-linked connection between essential hypertension, diabetes and autoimmunity.
Abnormal Whole-Body and Cellular (Erythrocytes) Turnover of 22Na+ in Normotensive Relatives of Probands with Established Essential Hypertension
Authors: Henningsen N. C. , Mattsson S. , Nosslin B. , Nelson D. , Ohlsson O.
Published: August 2015

1. Whole-body elimination rate of 22Na+ was decreased in normotensive or borderline first-degree relatives of hypertensive probands.

2. Whole-body potassium; exchangeable sodium and urine excretion of sodium, potassium and creatinine were similar in relatives and controls.

3. Erythrocyte net influx of 22Na+ was significantly increased in normotensive relatives.

4. Abnormal whole-body and cellular handling of sodium (22Na+) demonstrated in relatives indicates that this abnormality may have an important role in the development of essential hypertension in man.
Intralymphocytic Sodium in Hypertensive Patients: A Significant Correlation
Authors: Ambrosioni E. , Tartagni F. , Montebugnoli L. , Magnani B.
Published: August 2015

1. Intralymphocytic sodium concentration was measured in 50 patients with essential stable hypertension, 44 patients with labile hypertension and 40 subjects with normal blood pressure.

2. Intralymphocytic sodium concentration in normotensive subjects was significantly lower than in the other two groups.

3. The concentration was significantly correlated with mean blood pressure in the group as a whole and in the groups with stable and with labile hypertension. No correlation was found in normal subjects.
Clinical and Pathological Relevance of Erythrocyte Cation Fluxes Measurement in Hypertension
Authors: Garay R. P. , De Mendonca M. , Elghozi J. L. , Devynck M. A. , Dagher G. , Pernollet M. G. , Grichois M. L. , Ben-Ishay D. , Meyer P.
Published: August 2015

1. The clinical applications of a simple laboratory test for the diagnosis of essential hypertension were further investigated on a large number of patients (124 individuals).

2. The reduced erythrocyte ratio of Na+/K+ net fluxes observed in essential hypertensives might be secondary to a functional defect in a Na+—K+ co-transport system.

3. A similar reduction in the ratio of Na+/K+ net fluxes was also observed in erythrocytes of some normotensive subjects born of hypertensive parents and of genetically hypertensive rats. This suggests that the erythrocyte membrane defect follows the genetic transmission of hypertension.
Haemodynamics of Acth-Induced Hypertension in Sheep
Authors: Scoggins B. A. , Allen K. J. F. , Coghlan J. P. , Denton D. A. , Graham W. F. , Humphery T. J. , Whitworth Judith A.
Published: August 2015

1. Administration of adrenocorticotropic hormone (ACTH) to sheep produced increases in mean arterial pressure within 24 h associated with an increase in cardiac output and cardiac rate. Both cardiac output and blood pressure remained elevated over the 5 days of ACTH treatment.

2. Administration of ACTH during β-adrenoreceptor blockade resulted in an increase in blood pressure without changes in cardiac output at 24 h.

3. Administration of a combined steroid infusion over 5 days produced increases in cardiac output identical with the effects of ACTH but with a substantially smaller effect on blood pressure.

4. These data suggest that the observed changes in cardiac output produced by ACTH treatment may be associated with high blood concentrations of adrenocortical steroids rather than being necessary for the development of the hypertension.
Circulatory Changes during Pregnancy in Spontaneously and Renal Hypertensive Rats
Authors: Lundgren Y. , Karlsson K. , Ljungblad U.
Published: August 2015

1. Mean arterial pressure, heart rate, cardiac output (dye-dilution technique), stroke volume, total peripheral resistance (TPR), utero—placental blood supply (microsphere technique) and foetal weights were determined 2 days before expected birth in normotensive control (NC) rats, spontaneously hypertensive (SH) rats, rats with short-standing renal hypertension induced early in pregnancy and rats with established renal hypertension induced 4 weeks before pregnancy. Non-pregnant rats in comparable states served as controls.

2. In normal pregnancy cardiac output increased by 33% and blood pressure and TPR decreased by 17 and 38% respectively. The same principal changes were noted in SH rats and those with short-standing renal hypertension, but no changes were found in rats with established renal hypertension during pregnancy.

3. Myometrial and placental blood supply was lower in all hypertensive groups compared with NC rats, the reduction being 46 and 36% in SH rats and in rats with established renal hypertension as much as 74 and 68% respectively.

4. In SH rats foetal weights were reduced compared with NC rats, but despite the 68% reduction of placental blood flow in rats with established renal hypertension foetal weights were here unchanged.
A Circulating Humoral Pressor Agent in Dahl S Rats with Salt Hypertension
Authors: Tobian L. , Pumper Mary , Johnson Susan , Iwai J.
Published: August 2015

1. In Dahl S rats becoming hypertensive while on a diet of high NaCl content there appears to be a blood-borne humoral agent which produces vasoconstriction in a bioassay using the isolated hindquarters of rats.

2. This vasoconstrictor effect strongly suggests the presence of a humoral pressor agent or the lack of a vasodilator agent in the blood of hypertensive S rats.

3. The vasoconstrictor effect is not due to high renin concentrations.

4. This humoral vasoconstrictor action could partly account for the high vascular resistance in the hypertensive S rat.
Treatment of Mild Hypertension in Elderly Males
Authors: Morgan T. , Adam W. , Carney S. , Gibbard R. , Brown S. , Wheeler D.
Published: August 2015

1. Males, born between 1900 and 1925, with mild hypertension have been treated for periods varying from 300 to 2000 days.

2. The life and death status of all patients (except two) was known on 1st November 1978.

3. A group of patients with mild hypertension receiving treatment based on a thiazide diuretic had a greater mortality than the other drug-treated group.

4. The increased mortality was caused by an increased number of myocardial infarcts.

5. Elderly male patients with mild hypertension probably have preexisting vascular disease and therapy should not automatically be started. If therapy is started, β-adrenoreceptor-blocking drugs may be a preferred therapy.
Haemodynamics during Long-Term Thiazide Treatment in Essential Hypertension: Differences between Responders and Non-Responders
Authors: Van Brummelen P. , Veld A. Man In 't , Schalekamp M. A. D. H.
Published: August 2015

1. Blood pressure, systemic haemodynamics, plasma volume, renin and aldosterone were measured during placebo treatment and after 1, 4 and 12 weeks of hydrochlorothiazide in 13 patients with uncomplicated essential hypertension. Nine of these patients were also studied after 24 and 36 weeks of treatment.

2. Mean arterial pressure was lowered significantly during hydrochlorothiazide treatment. In seven patients the fall in mean arterial pressure was greater than 10% (responders); four of these were studied for 36 weeks. The remainder were considered non-responders.

3. Hydrochlorothiazide lowered cardiac output. The maximal decrease was observed after 12 weeks of treatment (P < 0·01). In responders this was followed by a return to pretreatment values and a significant decrease in total peripheral resistance, whereas in non-responders cardiac output remained reduced and total peripheral resistance was permanently elevated.

4. Changes in plasma volume, renin and aldosterone were not significantly different in responders and non-responders although non-responders tended to show a greater degree of plasma volume depletion and a more pronounced increase in plasma aldosterone.

5. Thus it is unlikely that the initial decrease in cardiac output is an important determinant of the long-term haemodynamic effect of thiazide diuretics.
Effect of Exercise in Hypertension Controlled with Metoprolol or Methyldopa
Authors: Stoker J. B. , Sreeharan N. , Linden R. J. , Barbour M. P. , Lorimer A. R. , Hillis W. S. , Lawrie T. D. V.
Published: August 2015

1. The adequacy of the control of essential hypertension during exercise was studied in patients whose resting blood pressure had been controlled for 1 year with either metoprolol or methyldopa.

2. Systolic blood pressure increased with exercise in both groups, the increase being significantly less in the metoprolol group than in the methyldopa group.
Objective Measurement of Performance during Acute Stress in Patients with Essential Hypertension: Assessment of the Effects of Propranolol and Metoprolol
Authors: Dunn F. G. , Lorimer A. R. , Lawrie T. D. V.
Published: August 2015

1. A standardized method of objectively measuring performance during simulated car driving is described.

2. The effect of a single dose of propranolol and metoprolol were compared with placebo in two groups of patients with untreated essential hypertension.

3. Performance was similar after β-adrenoreceptor-blocking agents or placebo.

4. Blood pressure response to stress persisted after administration of the blocking agents.
SK&F 92657, a Novel Antihypertensive Acting by Precapillary Vasodilatation and β-Adrenoreceptor Blockade
Authors: Taylor E. M. , Roe A. M. , Slater R. A.
Published: August 2015

1. The properties of a new antihypertensive agent, SK&F 92657, dl-3-[2-(3-t-butylamino-2-hydroxypropoxy)phenyl]-6-hydrazinopyridazine, have been studied.

2. The compound caused a sustained fall in blood pressure in several species as a result of precapillary vasodilatation, particularly in the renal and coronary vasculatures.

3. The β-adrenoreceptor-blocking actions of SK&F 92657 prevent reflex cardiac stimulation.
Systemic Haemodynamic Effects of Biofeedback in Borderline Hypertension
Authors: Messerli F. H. , Decarvalho J. G. R. , Christie Barbara , Frohlich E. D.
Published: August 2015

1. Six patients with borderline hypertension underwent training in exteroceptive biofeedback (BFB) in order to increase or decrease arterial pressure.

2. Systemic haemodynamics, intravascular volume and peripheral renin activity were determined before, during and after training sessions.

3. BFB training resulted in a significant reduction in mean arterial pressure (from 116 ± 4·6 to 101 ± 2·5 mmHg) mediated through a fall in total peripheral resistance; cardiac output, heart rate, intravascular volume and plasma renin activity remained unchanged.

4. In contrast, the increase or decrease of arterial pressure that occurred during BFB training was produced predominantly through changes in cardiac output and heart rate respectively, whereas total peripheral resistance under these circumstances remained unaffected.

5. The haemodynamic effects of BFB seem remarkably similar to the immediate or chronic effects of β-adrenoreceptor blockade, initially producing a fall in cardiac output followed by a reduced arterial pressure associated with a decreased total peripheral resistance.
Sequential Changes in Plasma Noradrenaline during Bicycle Exercise
Authors: Watson R. D. S. , Hamilton C. A. , Jones D. H. , Reid J. L. , Stallard T. J. , Littler W. A.
Published: August 2015

1. Forearm venous plasma noradrenaline, heart rate and intra-arterial blood pressure were measured sequentially during and after upright bicycle exercise in five normotensive and six hypertensive patients.

2. Plasma noradrenaline increased significantly between 4 and 8 min during exercise.

3. On stopping exercise blood pressure and heart rate decreased rapidly whilst plasma noradrenaline increased in each subject to reach a maximum at a median time of 108 s after exercise.

4. Plasma noradrenaline decreased in five of six normotensive patients between the end of exercise and 2 min after exercise performed in the supine position.

5. Evidence in favour of a reflex increase in sympathetic activity after upright exercise is discussed.
Metabolism of Vasoactive Hormones in Human Isolated Lung
Authors: Al-Ubaidi F. , Bakhle Y. S.
Published: August 2015

1. The metabolism of some vasoactive hormones perfused through pulmonary vessels was studied in samples of human lung obtained at operations.

2. 5-Hydroxytryptamine was inactivated and this inactivation was inhibited by desmethylimipramine and mebanazine.

3. β[14C]Phenylethylamine was also metabolized in human lung.

4. Prostaglandin E2 was inactivated and this inactivation inhibited by bromocresol green and frusemide.

5. About 10% of the radioactivity from infused [14C]arachidonic acid emerged from the lung and a small amount of biological activation occurred.

6. Of [14C]arachidonic acid retained by the lung, most was present in phospholipid with lesser amounts in neutral lipid and free acid fractions.

7. The fate of the hormones studied was qualitatively similar to their fate in animal lungs.
Creatine Kinase-1 is Principally Inactivated in Serum by Complexing with Immunoglobulin-G
Authors: Nealon D. A. , Henderson A. R.
Published: August 2015

1. The stability of enzyme activity of the creatine kinase-l-immunoglobulin-G complex has been determined at 37°C, 4°C and −20°C in heat-inactivated serum and buffer.

2. The complex was formed by incubating creatine kinase-1 and immunoglobulin G at 37°C for 30 min. It was isolated by Sephadex G-100 column chromatography.

3. At all temperatures the complex suspended in buffer was about twice as stable as it was in heat-inactivated serum. Stability decreased in the sequence of 4°C, 37°C and −20°C. Therefore all isolations of the complex were carried out at 4°C.

4. At 37°C the decay of enzyme activity of the complex was found to be biphasic first order. In serum the Kd values were −0·045 min−1 and −0·0028 min−1, and in buffer −0·023 min−1 and −0·0016 min−1.

5. From column-chromatography experiments it was found that between 10 and 20% of the total creatine kinase-1 was involved in the complexing reaction after a 30-min incubation.

6. With this 10·20% proportion it can be calculated that the overall t0·5 for the decay of total creatine kinase-1 activity must be in the range 95–201 min. This finding suggests, by comparison with other published data, that the enzyme—immunoglobulin complex is the main route of creatine kinase-1 catabolism in serum.

7. The difference between serum and buffer decay values for the complex is possibly due to the presence of cystine, urate and other substances in serum, which are additional potent creatine kinase inhibitors.
Cardiovascular Responses to Graded Reductions of Central Blood Volume in Normal Subjects and in Patients with Diabetes Mellitus
Authors: Bennett T. , Hosking D. J. , Hampton J. R.
Published: August 2015

1. Cardiovascular responses to graded increments of lower body negative pressure were studied in non-diabetic subjects and in patients with diabetes mellitus.

2. In all subjects, low levels of negative pressure (which did not affect significantly systemic arterial pressure) induced forearm vasoconstriction, suggesting normal function of the ‘low pressure’ cardiopulmonary baroreflex. However, in some diabetic patients the response to higher levels of negative pressure was abnormal, and it seems likely that although afferent mechanisms were intact there was impairment of efferent vasoconstrictor function.

3. Changes in R—R interval were linearly related to changes in systolic blood pressure induced by higher levels of negative pressure. The slope of the relationship was taken as the sensitivity of the ‘high pressure’ arterial baroreflex; diabetic patients showed a reduced sensitivity compared with normal subjects. Furthermore, in diabetic patients, abnormalities of R—R interval control were more common than abnormalities of vasoconstrictor function, suggesting that heart-rate control is impaired earlier than vasomotor function in diabetic autonomic neuropathy.
Prostaglandins as Mediators of Bone Resorption in Renal and Breast Tumours
Authors: Greaves M. , Ibbotson K. J. , Atkins D. , Martin T. J.
Published: August 2015

1. Amounts of prostaglandin E and prostaglandin F have been measured by radioimmunoassay in extracts of renal cortical carcinoma and benign and malignant breast tumours after solvent extraction and column chromatography.

2. Substantial amounts of prostaglandin E were found in extracts of benign and malignant breast tumours and in renal tumours. Much lower amounts of prostaglandin F were present in all tumour types.

3. Co-cultivation of tumour explants with mouse calvaria led to significant bone resorption in 10 of 13 renal carcinomas, three of eight malignant breast tumours, and two of nine benign breast tumours. Tumours associated with bone resorption had higher concentrations of prostaglandin E in culture media at the end of incubation than did non-resorbers.

4. Indomethacin (14 μmol/l) greatly reduced bone resorption in the presence of the tumour, but this was not always complete, particularly with breast tumours. Indomethacin had no effect on prostaglandin-induced bone resorption. Theophylline (2·2 mmol/l) significantly increased prostaglandin E production and resorption by an effect on the tumour.

5. It is concluded that prostaglandins may be important in mediating the effects of renal cortical carcinoma and possibly breast cancer on bone destruction. A non-prostaglandin mechanism may also contribute to bone destruction by breast carcinoma.
Effect of Spironolactone on Aldosterone Regulation in Man
Authors: Gaillard R. C. , Riondel A. M. , Chabert P. , Vallotton M. B.
Published: August 2015

1. The action of spironolactone, a well-known antagonist of mineralocorticoids, on aldosterone regulation was investigated in normal young men to see whether it also acted as an inhibitor of biosynthesis in the adrenal gland.

2. The action of spironolactone was studied under three different conditions: (a) during 3 days of treatment with spironolactone; (b) during 1 day of combined administration with long acting adrenocorticotropic hormone (ACTH); (c) in the course of a continuous infusion of angiotensin II.

3. Spironolactone did not alter the metabolism of aldosterone or cortisol.

4. Spironolactone administration produced: (a) a marked increase in both aldosterone secretion and plasma renin activity, but no change in the plasma aldosterone/plasma renin activity ratio, the cortisol secretion rate or the plasma corticosterone concentration; (b) no blunting in the response of aldosterone to stimulation by ACTH; (c) no decrease in plasma aldosterone concentration when changes of the endogenous renin activity were prevented by an infusion of angiotensin II.

5. These results do not confirm the considerable inhibition of aldosterone excretion found by others after spironolactone administration to normal men. We observed no inhibition of aldosterone biosynthesis by spironolactone. However, a minimal, short-lived inhibition of biosynthesis cannot be excluded, but this possible action of spironolactone plays at best a minor role in the action of this drug.
Assessment of Plasma 25-Hydroxyvitamin D Response to Ultraviolet Irradiation over a Controlled Area in Young and Elderly Subjects
Authors: Davie M. , Lawson D. E. M.
Published: August 2015

1. The response of 25-hydroxyvitamin D [25-(OH)D] to artificial ultraviolet irradiation applied to a known area of dorsal skin was investigated in 18 subjects, small quantities of ultraviolet energy being used. Ultraviolet irradiation was administered on days, 1, 3, 5, 8, 10, 12, 15 and 17, a total of 15 min being delivered over this time. In 15 subjects plasma 25-(OH)D showed a significant increase after a total of 15 min exposure but three subjects failed to demonstrate any increment. Plasma 25-(OH)D did not increase in any subject after 2·5 min of ultraviolet irradiation (irradiation on days 1 and 3).

2. Responses were compared in young and old, in male and female and in normal and osteomalacic subjects. No significant difference in response was found between these groups.

3. When plasma volume was taken into account, it was possible to calculate the increase in nmol of plasma 25-(OH)D/cm2 skin irradiated. This was 0·024 nmol/cm2 with no sex difference, over the 17 days of irradiation.

4. Exposure to ultraviolet irradiation over a small area of dorsal skin led to a rapid rise of plasma 25-(OH)D in most subjects with a subsequent plateau in subjects studied for up to 15 min total exposure. This contrasted with the prolonged increase in plasma 25-(OH)D continuing over several weeks in response to whole-body ultraviolet irradiation. This may indicate that cutaneous synthesis of vitamin D is rapid but limited, and that the considerable rise in plasma 25-(OH)D during whole-body irradiation may originate from vitamin D synthesized during the first few exposures.
Indium (111In)-Labelled Human Platelets: Optimal Method
Authors: Hawker R. J. , Hawker Linda M. , Wilkinson A. R.
Published: August 2015

1. A detailed laboratory method is described for the labelling of human platelets with [111In]indium oxine. The 45 min method is simple, requires only 26 ml of blood and is suitable for routine clinical use.

2. After the labelling and resuspension of the platelets in plasma, aggregation responses to both adenosine diphosphate and collagen were similar to those of normal platelet-rich plasma. Less than 5% of the [111In]indium oxine was released by secretory functions of platelets.

3. Labelling efficiencies of 90·1 ± 4·29% (n = 28) were achieved in 60 s by normal concentrations of plasma-free platelet suspensions.

4. Platelet survival in vivo in healthy volunteer subjects follows a linear function with a survival time of 8·44 ± 0·18 days.
Practical Importance of a Preceding Full Inhalation or Exhalation upon the Measurement of Airway Resistance
Authors: Higenbottam T. , Clark T. J. H.
Published: August 2015

1. Airway resistance was measured close to functional residual capacity before and after a full inhalation of total lung capacity, as well as before and after a full exhalation to residual volume.

2. The effects of these volume manoeuvres upon airway resistance (and associated lung volume) were determined in four resting normal male subjects and in six normal men during experimentally induced bronchoconstriction after breathing an air/histamine mist from a Wright's nebulizer.

3. In four men the duration of the effect of a full inhalation upon airway resistance after induced bronchoconstriction was assessed separately.

4. Neither a full inhalation nor a full exhalation altered airway resistance under normal conditions. However, a full inhalation reduced airway resistance in the presence of bronchoconstriction and this effect lasted for a period of 45 s. Even with bronchoconstriction, a full exhalation had no effect on airway resistance.

5. Account must therefore be taken of the potential reduction in airway resistance which may result from a full inhalation, particularly when indirect measurements of airway function which involve a full inhalation, such as forced spirometry, are used to assess airway obstruction.
Effect of a Natural and Artificial Menopause on Serum, Urinary and Erythrocyte Magnesium
Authors: Lindsay R. , Hart D. M. , Forrest C.
Published: August 2015

1. Serum, urinary and erythrocyte magnesium concentrations were measured in groups of premenopausal, postmenopausal and oophorectomized women.

2. Serum and urinary magnesium were both significantly higher in postmenopausal and oophorectomized women than in the premenopausal group.

3. Oestrogen therapy reduced both serum and urinary magnesium values in oophorectomized women to premenopausal concentrations.

4. Erythrocyte magnesium concentrations were not affected by menstrual status or oestrogen therapy.
The Relative Merits of Various Techniques for Measuring Radiocalcium Absorption
Authors: Wootton R. , Reeve J.
Published: August 2015

1. One-hundred and ten double-tracer (47Ca/45Ca or 47Ca/85Sr) calcium-absorption studies were performed in patients with a variety of metabolic bone disorders. A computer program was written to fit plasma radioactivity data from both oral and intravenous tracers by spline functions and to deconvolve points interpolated from the fitted curves to obtain the spectrum of *Ca transit times from mouth to plasma.

2. Methodological precision in the estimation of fractional absorption, maximum and mean rates of absorption and mean transit time was not substantially degraded by the normal uncertainties of sample counting.

3. From the results of 35 studies in which 85Sr was given as an additional intravenous tracer, it is concluded that the use of oral 47Ca and intravenous 85Sr is an acceptable alternative to the 47Ca/45Ca combination and offers considerable practical advantages.

4. The single-tracer whole-body retention and faecal collection methods for estimating calcium absorption were found to be sensitive to variations in endogenous excretion and bone accretion of calcium, making these methods unsuitable for some purposes.

5. The single-tracer method of Marshall and Nordin (1969) provided reasonable estimates of absorption rates, but the simplifications inherent in this model give rise to unpredictable systematic uncertainties in the calculation of mean absorption rates.

6. The double-isotope (47Ca oral, 85Sr intravenous) calcium-absorption test, in which blood is sampled serially over 6 h, is the method of choice for the detailed investigation in vivo of the physiological mechanisms of radiocalcium absorption by the undisturbed gut.
Rat Liver Storage Iron and Plasma Ferritin during d-Galactosamine-Hcl-Induced Hepatitis
Authors: Zuyderhoudt F. M. J. , Jörning G. G. A. , De Haan J. G. , Samson G. , Van Gool J.
Published: August 2015

1. d-Galactosamine-HCl induces toxic hepatitis in the rat and was used as a model to study some aspects of iron metabolism during liver cell damage. Some changes in iron metabolism were similar to those encountered in human acute viral hepatitis.

2. During the first 3 days of liver cell damage induced by galactosamine, liver depot iron and especially ferritin iron decreased by approximately 20%. Plasma ferritin rose, with a peak mean value which was approximately 20 times the concentration measured in normal rats.

3. During the acute phase, plasma ferritin did not accurately reflect the change in the level of liver depot iron.

4. During and after the acute phase, liver depot iron increased after an initial decrease. The non-ferritin depot iron fraction was elevated approximately 75% compared with the value in normal rats. This increase in non-ferritin iron was probably caused by increased erythrocyte catabolism in the liver and recapture followed by catabolism of liver ferritin that had leaked into the blood.
The Effects of Isoprenaline, Atropine and Dobutamine on Ventricular Volume Curves Obtained by Radionuclide Ventriculography
Authors: Muir A. L. , Hannan W. J. , Sapru R. P. , Boardman A. K. , Wraith P. K. , Brash H. M.
Published: August 2015

1. The purpose of this study was to determine whether events early in systole, a period which may be more descriptive of ventricular performance than the average of events in systole, can be determined by multiple gated radionuclide cardiac blood pool imaging.

2. We examined 16 ventricular volume curves, using a digital filtering method in the frequency domain to smooth statistical noise. Ejection fraction was unchanged by such filtering but the peak rate of change of volume during systole was greatly affected by different bandwidths. Therefore we derived an index, the mean ejection time, which is influenced by changes in the shape of the systolic portion of the volume curve but is unchanged when measured from curves treated by different filter bandwidths.

3. We infused isoprenaline (2 μg/min; eight patients), atropine (1.2 mg; eight patients) or dobutamine (360 μg/min; six patients).

4. Isoprenaline and atropine caused a similar increase in heart rate (isoprenaline + 27 beats/min; atropine + 20 beats/min) but after dobutamine there was little change in heart rate (+4 beats/min). After isoprenaline and dobutamine ejection fraction increased (0.51 ± sem 0.04 control; 0.73 ± 0.04 after isoprenaline; 0.53 ± 0.03 control; 0.65 ± 0.06 after dobutamine) but was unchanged by atropine (0.46 ± 0.07 control; 0.48 ± 0.07 after atropine).

5. The mean ejection time decreased by 55 ms after isoprenaline, by 49 ms after dobutamine but by only 14 ms after atropine. Changes in peak rate of change of volume in systole were more variable.

6. Radionuclide gated blood pool studies can be used to study the effects of pharmacological intervention on events in early systole and the variable ‘mean ejection time’ is independent of curve-fitting techniques.
Enzyme Induction and Serum and Lipoprotein Lipids: A Study of Glutethimide in Normal Subjects
Authors: Bolton C. H. , Jackson LYN , Roberts C. J. C. , Hartog M.
Published: August 2015

1. Serum and lipoprotein cholesterol and triglycerides were measured before, during and after the administration of glutethimide (500 mg daily) for 21 days to six healthy volunteer subjects.

2. Evidence of enzyme induction was provided by significant rises in d-glucaric acid excretion and antipyrine clearance.

3. Concentrations of total serum cholesterol, very-low-density-lipoprotein-, low-density-lipoprotein-and high-density-lipoprotein-cholesterol rose significantly during treatment.

4. The time course of these changes was delayed in comparison with the rise and fall in d-glucaric acid excretion.

5. There was no change in the triglyceride content of either whole serum or lipoprotein fractions at any time during the trial.

6. The study provides further evidence that enzyme-inducing agents cause a rise in certain lipid concentrations.
Accumulation of Sulphur-Containing Amino Acids Including Cysteine-Homocysteine in Patients on Maintenance Haemodialysis
Authors: Wilcken D. E. L. , Gupta Vatsala J. , Reddy S. G.
Published: August 2015

1. Plasma sulphur-containing amino acids were measured in 19 patients with renal failure on chronic haemodialysis and in 22 normal subjects, to determine the rate of accumulation of these amino acids in chronic azotaemia.

2. Cysteine-homocysteine mixed disulphide was significantly increased in patients before dialysis and homocystine was detected in low concentration in 10 patients. Cystine and taurine were also increased. Changes in other neutral and acidic amino acids were similar to those reported in chronic renal insufficiency.

3. In 3–4 h of dialysis serum creatinine was decreased by a mean of 55%, cysteine-homocysteine by 41%and cystine by 58.5%(P<0.001 for each). Methionine concentrations were normal throughout.

4. We conclude that sulphur-containing amino acids, except methionine, accumulate in chronic renal failure as rapidly as creatinine.
The Effect of Captopril on Blood Pressure and Angiotensins I, II and III in Sodium-Depleted Dogs: Problems Associated with the Measurement of Angiotensin II after Inhibition of Converting Enzyme
Authors: Morton J. J. , Tree M. , Casals-Stenzel J.
Published: August 2015

1. Changes in arterial blood pressure, blood angiotensin I, plasma angiotensin II and plasma angiotensin III were measured in conscious sodium—depleted dogs after infusion of captopril, an orally active inhibitor of converting enzyme.

2. Angiotensins II and III were measured after chromatography to remove angiotensin I, which increased in concentration after inhibition of converting enzyme and which interfered in the direct assay for angiotensin II.

3. Infusion of captopril at 20, 200, 2000 and 6000 μg h−1 kg−1, each for 3 h, produced a rapid fall in blood pressure and in concentration of angiotensin II. Angiotensin II was undetectable at 6000 μg h−1 kg−1 (mean pre-infusion value for all samples was 39 ± sd 15 pmol/I, n = 14)

4. The percentage fall in blood pressure correlated with the percentage fall in plasma angiotensin II (r = 0.65, P<0.001)

5. These results suggest that the initial fall in blood pressure may be mediated in part by the suppression of angiotensin II.

6. Blood angiotensin I concentration rose with each rate of infusion of drug to a maximum 16-fold increase at 6000 μg h−1 kg−1 (26−416 pmol/l). The rise in angiotensin I was inversely related to the fall in angiotensin II (r = −0.68, P<0.001)
Human Lung Adrenoreceptors Studied by Radioligand Binding
Authors: Barnes P. J. , Karliner J. S. , Dollery C. T.
Published: August 2015

1. Direct radioligand—binding techniques have been used to characterize and quantify adrenoreceptors in human peripheral lung tissue removed at thoracotomy from ten patients, nine of whom had evidence of obstructive airways disease.

2. [3H]Dihydroalprenolol was used to characterize β–adrenoreceptor sites and [3H]prazosin to identify α–adrenoreceptor sites. Binding of both ligands showed saturability, high affinity, rapid kinetics, reversibility and stereospecificity. The rank order of agonists and antagonists inhibiting specific binding correlated well with known physiological potencies. Specificity of [3H]dihydroal-prenolol binding suggested that the population of lung β–adrenoreceptors is predominantly of the β2 subtype.
[15N]Glycine Metabolism in Normal Man: the Metabolic α-amino-nitrogen Pool
Authors: Jackson A. A. , Golden M. H. N.
Published: August 2015

1. [15N]Glycine was infused into fed, fasted or acidotic humans.

2. In all metabolic states there was considerable transfer of labelled nitrogen to urea and ammonia, but alanine and glutamate did not become enriched.

3. The findings show that free exchange of nitrogen between all amino acids does not take place. Glycine, serine, threonine, lysine and histidine cannot be considered part of the α-aminonitrogen pool as classically conceived, although they form up to one-half of that pool.
Histamine Receptors in Normal Human Bronchi
Authors: Eiser Noemi M. , Mills Jane , McRae K. D. , Snashall P. D. , Guz A.
Published: August 2015

1. Nine normal subjects inhaled increasing concentrations of histamine aerosol from an aerosol generator attached to a breath-actuated dosimeter. The responses were monitored by measuring specific airways-conductance in a body plethysmograph, and the results were expressed as cumulative log dose-response curves. On separate days, histamine challenges were repeated after intravenous injections of sodium chloride solution (placebo), or an H1-receptor antagonist chlorpheniramine, or an H2-receptor antagonist cimetidine, or H1- and H2-receptor antagonists together. The anticholinergic activity of chlorpheniramine was estimated by comparing the effect of chlorpheniramine and atropine on methacholine challenge.

2. In all subjects the response to histamine was reproducible. Analysis of the variance showed that placebo did not alter the histamine dose-response curve significantly. In contrast, chlorpheniramine produced a large shift in the histamine dose-response curve to the right and cimetidine produced a significant shift of this curve to the right only at the highest dose of histamine. A combination of cimetidine and chlorpheniramine produced a shift not significantly different from that seen with chlorpheniramine alone. Chlorpheniramine showed no significant anticholinergic activity in this study.

3. In the normal subjects histamine-induced bronchoconstriction appeared to be mediated predominantly by the H1-receptors. The H2-receptor contributed very little to this bronchoconstriction.
Subcellular Fractionation Studies of Human Gastric Antrum: Localization of the Mucosal Peptide Hormones
Authors: Dawson J. , Bryant M. G. , Bloom S. R. , Peters T. J.
Published: August 2015

1. Analytical subcellular fractionation techniques have been applied to endoscopic human gastric antral biopsies to study the localization of gastrin, somatostatin, vasoactive intestinal peptide and the properties of the principal subcellular organelles.

2. The peptide hormones, detected by radio-immunoassay, showed particulate localizations with single peaks in the density gradients for somatostatin (modal density 1.23) and vasoactive intestinal peptide (modal density 1.17). Gastrin showed a more complex distribution with a distinct peak (modal density 1.18) and a substantial shoulder extending into the denser regions of the gradient.

3. The following organelles, characterized by their marker enzymes, were located in the density gradients: plasma membrane (5′-nucleotidase), mitochondria (malate dehydrogenase), peroxisomes (catalase), lysosomes ((β-N-acetyl-d-glucosaminidase), endoplasmic reticulum (neutral α-glucosidase), cytosol (lactate dehydrogenase).

4. This technique can be applied to investigate disease of the gastric antrum at a subcellular level.
Pathways of Transepithelial Potassium Movement in the Epithelium of Distal Colon in Man
Authors: Kermode J. C. , Edmonds C. J.
Published: August 2015

1. Methods for studying the kinetics of movement of radioactive tracers across human distal colonic epithelium have been developed for use in vivo and applied to examination of trans-epithelial transfers of potassium.

2. During absorption of 43K from the lumen, two potassium pools, A and B, in the epithelium were identified, having mean turnover half-times of 16 and 87 min respectively. On average about 50% of the potassium lumen-to-plasma flux and most, if not all, of the potassium plasma-to-lumen flux took place through pool A. The transcellular pathway (equated with pool B) appeared to be of relatively little significance in transepithelial movement of potassium in the human distal colon.

3. Sodium and chloride movements were unaffected when lithium was present in the luminal solution, but the potassium secretion rate was nearly trebled due to increased plasma-to-lumen flux through the fast turnover pool A.

4. The permeability of the epithelium to potassium, as judged by the plasma-to-lumen fluxes, greatly exceeded that to sodium. This appeared to depend on a special highly selective potassium channel which differed from the shunt pathway in possessing definite capacity.