bluuebunny/crossref_metadata_2025 huggingface dataset:
Validation of a Doppler technique for beat-to-beat measurement of cardiac output
Authors: Mehta Nawzer , Iyawe Vincent I. , Cummin Andrew R. C. , Bayley Susan , Saunders Kenneth B. , Bennett E. David
Published: August 2015

1. We have measured aortic flow in the ascending aorta in man with a Bach-Simpson BVM 202 blood velocity meter, and aortic root diameter by M-mode echocardiography, and thus derived beat-to-beat cardiac output (Q).

2. We tested the technique in 21 patients (53 comparisons) with various cardiovascular problems against a thermodilution method, and in four normal subjects at rest and two levels of exercise (50 and 100 W) against a nitrous oxide rebreathing method.

3. We obtained excellent overall correlation in a range of 0.5–10 litres/min (r = 0.98, n = 77, sy,x = 0.48 litre/min), the formula for the least squares regression being: (Q Doppler) = 0.95 (Q Thermodilution/N2O) + 0.11 litre/min.

4. The Doppler signal is sufficiently noise-free to obtain maximum acceleration of flow from the first derivative of velocity.
Tremor: an alternative approach for investigating adrenergic mechanisms in thyrotoxicosis?
Authors: Abila B. , Lazarus J. H. , Kingswood J. C. , Marshall R. W. , Wilson J. F. , Richens A.
Published: August 2015

1. The effects of nadolol (or placebo) and carbimazole on thyrotoxic tremor were investigated in 18 thyrotoxic patients.

2. Both nadolol and carbimazole produced significant reductions in tremor power although nadolol did not cause any change in serum free tri-iodothyronine and free thyroxine concentrations.

3. The results are discussed in terms of the pathogenesis of thyrotoxic tremor and the potential usefulness of tremor in the investigation of adrenergic mechanisms in thyrotoxicosis.
Effects of age on body temperature and blood pressure in cold environments
Authors: Collins K. J. , Easton J. C. , Belfield-Smith Hazel , Exton-Smith A. N. , Pluck R. A.
Published: August 2015

1. Mean deep body temperature fell by 0.4 ± 0.1 (sd) °C in five sedentary, clothed 63–70 year old men and by 0.1 ±0.1°C in four young adults after 2 h exposure in still air at 6°C (P < 0.001).

2. The mean increase in systolic and diastolic pressure was significantly greater (P < 0.002) in the older subjects (24 ± 4 mmHg systolic, 13 ± 4 mmHg diastolic) than in the young (14 ± 6 mmHg systolic, 7 ± 3 mmHg diastolic) after 2 h at 6°C. A small rise in blood pressure occurred in the older men at 12°C, but there was no increase in either group at 15°C.

3. The association of variables is particularly marked between systolic blood pressure and core temperature changes at 6°C.

4. There were no appreciable cold-adaptive changes in blood pressure or thermoregulatory responses after 7–10 days repeated exposure to 6°C for 4 h each day.

5. Blood pressure elevation in the cold was slower but more marked in the older men. These changes in blood pressure may provide a possible basis for delineating low domestic limiting temperature conditions.
β-Adrenoceptor responsiveness and plasma catecholamines as determinants of cardiovascular reactivity to mental stress
Authors: Eisenhofer G. , Lambie D. G. , Johnson R. H.
Published: August 2015

1. Twenty-five normotensive men were subjected to two periods of mental stress involving a cognitive task and a competitive electronic game. Plasma catecholamines, heart rate and blood pressure were measured before and during mental stress. Responsiveness to β-adrenoceptor stimulation was also determined in each subject by measurement of heart rate responses to bolus injections of isoprenaline.

2. Both periods of mental stress were associated with significant increases in systolic and diastolic blood pressures, heart rate and plasma adrenaline, but not plasma noradrenaline. Heart rate responses to mental stress varied widely, with increases ranging from 1 to 48 (mean ± sd 13.5 ± 10.6) beats/min for the cognitive task and from 2 to 49 (20.4 ± 14.0) beats/min for the electronic game. Systolic blood pressure responses also varied widely and showed significant positive correlations with heart rate responses.

3. Significant relationships were found between heart rate responses to both forms of mental stress and cardiac sensitivity to isoprenaline, subjects with low responsiveness to β-adrenoceptor stimulation tending to have smaller heart rate responses to mental stress than subjects with high responsiveness to β-adrenoceptor stimulation. Relationships were also found between plasma adrenaline responses and heart rate responses to mental stress, although these did not reach significance. Considerably improved relationships were found when heart rate responses were correlated with a single variable generated from the product of the adrenaline response and the inverse of the dose of isoprenaline required to raise heart rate by 25 beats/min.

4. It is concluded that wide variation is shown between different individuals in responsiveness to β-adrenoceptor stimulation and that this is an important factor in the variability between individuals in heart rate and systolic blood pressure responses to mental stress. Both catecholamines and adrenoceptor-mediated responses to catecholamines should be examined when determining the physiological basis for differences in cardiovascular reactivity to mental stress between individuals or groups.
Right ventricular hypertrophy and polycythaemia in rats after intermittent exposure to hypoxia
Authors: Moore-Gillon J. C. , Cameron I. R.
Published: August 2015

1. Six groups of 20 male adult rats were maintained in an environmental chamber, each group for a period of 28 days. One group breathed air throughout its experimental period, and a second group breathed a normobaric atmosphere of 12% oxygen. The other four groups were exposed to this hypoxic atmosphere for only a proportion of each 24 h cycle: 2, 4 and 12 h daily, and eight periods of 30 min daily.

2. After 28 days, measurement was made, in each rat, of right ventricule (RV) weight and of red cell mass (RCM) by using 51Cr-labelled rat erythrocytes.

3. In the normoxic control group, RV weight corrected for log body weight in grams was 63.2 ± 1 mg/log body wt. and RCM was 2.02 ± 0.05 ml/100 g body wt. This was significantly less than in the group hypoxic for only 2 h each day for 28 days: RV weight 66.6 ± 0.8 mg/log body wt. (P < 0.05) and RCM 2.27 ± 0.05 ml/100g body wt. (P < 0.05). Greater increases compared with control were observed in all the other hypoxic groups. There was no significant difference in the increases in RV weight and RCM produced by daily hypoxia in a 4 h continuous period and daily hypoxia in eight 30 min periods.

4. The possible role of intermittent hypoxia in producing polycythaemia and pulmonary hypertension has been the subject of much speculation. Our results show that intermittent hypoxia is a potent stimulus to erythropoiesis and to pulmonary hypertension, reflected in RV hypertrophy. They support the view that abnormalities of respiration during sleep may be responsible for the polycythaemia and cor pulmonale seen in some patients with sleep apnoea syndromes and with chronic obstructive airways disease.
Kinetics of bumetanide-sensitive Na+-K+ co-transport in erythrocytes of essential hypertensive patients
Authors: Delva Pietro , De Gasperi Mario , Degan Maurizio , Covi Grazia , Lechi Alessandro
Published: August 2015

1. Outward bumetanide-sensitive Na+-K+ co-transport was studied in the erythrocytes of 51 subjects, 24 normotensive subjects and 27 hypertensive patients, matched for sex and age.

2. Three kinetic parameters of this cation transport system were considered: velocity of efflux at saturating internal sodium (Nai) concentrations (Vmax.), apparent affinity for sodium (K50%) and index of co-operativity among Nai sites (Hill's n).

3. We correlated these values with clinical and laboratory data determined routinely in hypertension.

4. There were no significant differences between normotensive and hypertensive subjects for the values considered and we did not find any significant correlations between co-transport and clinical data.
d-Sotalol: a new potent class III anti-arrhythmic agent
Authors: Taggart Peter , Sutton Peter , Donaldson Robert
Published: August 2015

1. We have compared the effect of a new drug d-sotalol which has minimal β-blocking action with the parent (β-blocking) compound dl-sotalol on monophasic action potential (MAP) duration in open-chested dogs. In seven experiments d-sotalol was administered in intravenous bolus doses of 1.5, 3 and 6 mg/kg given at 10 min intervals. In a further seven experiments dl-sotalol was administered using the same dosage regimen.

2. The animals were anaesthetized with chloralose and urethane. Atrioventricular block was created by injection of the bundle of His with 0.1 ml of 40% formalin in order to ensure capture by ventricular pacing. After prior β-blockade with propranolol (0.25 mg/kg), simultaneous epicardial and endocardial MAP were recorded at paced heart rates of 100 and 150 beats/min after each bolus injection. d-Sotalol and dl-sotalol showed similar prolongation of MAP duration (measured at 90% repolarization) in both endocardial and epicardial recording at both paced heart rates.

3. These results show that the dextro-isomer of sotalol possesses similar class III action to the parent compound and that this action is homogeneous with respect to left ventricular endocardium and epicardium at heart rates of 100 beats/min and 150 beats/min over a wide dose range. d-Sotalol may be a useful anti-arrhythmic agent in man.
Baroreflex sensitivity and pressor responses in a rat model of uraemia
Authors: Watson Alan J. , Di Pette Donald
Published: August 2015

1. Baroreflex sensitivity and pressor responsiveness to exogenous noradrenaline, angiotensin II and arginine vasopressin were determined in a rat model of uraemia.

2. The slope of the regression line relating Δheart rate to Δblood pressure after phenylephrine administration was significantly less in the renal failure group than the normal control group, indicating a reduction of baroreflex sensitivity in the setting of uraemia.

3. The pressor response to noradrenaline and angiotensin II was significantly less in the renal failure group whereas there was no difference in Δblood pressure on administration of arginine vasopressin.

4. It is concluded that diminished baroreflex sensitivity does not contribute to the pathogenesis of hypertension in uraemia by the hypothesized mechanism of allowing the pressor effect of endogenous pressor substances to go unbuffered.
Sleep apnoea in alcoholic patients after withdrawal
Authors: Tan E. T. H. , Lambie D. G. , Johnson R. H. , Robinson B. J. , Whiteside E. A.
Published: August 2015

1. Respiration during sleep was studied in 16 withdrawn alcoholic patients and in 12 control subjects.

2. The alcoholic patients had increased numbers of central (P < 0.01) and of obstructive (P < 0.05) apnoea and of hypopnoea episodes (P < 0.01) as compared with controls.

3. Significant positive associations were found between the frequencies of central apnoea (P < 0.05) or hypopnoea (P < 0.01) and clinical evidence of central nervous system damage in the alcoholic patients. Hypopnoea also showed a significant association with vagal neuropathy (P < 0.05), assessed by tests of cardioreflexes.

4. We conclude that abnormal respiratory events are common in abstinent alcoholic patients and that they are likely to be at least partly related to nervous damage.
The effect of hypoglycaemia on visual function: a clinical and electrophysiological study
Authors: Harrad R. A. , Cockram C. S. , Plumb A. P. , Stone S. , Fenwick P. , Söunksen P. H.
Published: August 2015

1. Disturbance of vision commonly accompanies hypoglycaemia. This study was designed to investigate the nature of the visual disturbance, the blood glucose threshold at which the disturbance occurred and the physiological basis.

2. Measurements were made of the corrected visual acuity, colour vision (100 Hue test), visual evoked potentials (VEP), electroencephalography (EEG) frequency analysis and psychometry (digit recall) during stepwise induction of controlled hypoglycaemia produced by an intravenous insulin infusion. Six male volunteers and five insulin-dependent diabetic subjects were studied.

3. During hypoglycaemia corrected visual acuity was unchanged. Colour vision was significantly impaired. Baseline VEP were normal in both groups but significantly prolonged during hypoglycaemia (mean increment 10.8 ms) and increased by >5 ms in nine out of 11 subjects. Quantitative EEG analysis demonstrated slowing with a power density spectral shift from fast α to slow α, θ and δ which correlated with VEP latency and amplitude changes.

4. The findings have clinical implications. A deterioration in colour vision is likely to impair the ability to read reagent strips by eye. VEP measurements in diabetic patients are likely to be misleading if hypoglycaemia is present; EEG changes are a sensitive index of cortical dysfunction during hypoglycaemia and provide a theoretical basis for developing a portable device to detect early hypoglycaemia.
Effect of natural and synthetic atrial natriuretic factor on arterial blood pressure, natriuresis and cyclic GMP excretion in spontaneously hypertensive rats
Authors: Pang Stephen C. , Hoang Minh-Chau , Tremblay Johanne , Cantin Marc , Garcia Raul , Genest Jacques , Hamet Pavel
Published: August 2015

1. The differential effects of extracted and synthetic atrial natriuretic factor (ANF) on arterial blood pressure, natriuresis, and cyclic GMP excretion were studied in normotensive (WKY) and spontaneously hypertensive (SHR and SHRSP) rats.

2. Atrial extracts or synthetic (101–126)-ANF decreased arterial blood pressure in all tested animals, but the blood pressure-lowering effect was more pronounced in hypertensive than in normotensive rats. ANF-induced diuresis and natriuresis were two- to three-fold higher in the hypertensive groups. However, a several-fold increase in total urinary cyclic GMP level after the infusion of ANF was essentially equal in the three groups.

3. Our data suggest that acute infusion of ANF reveals a defect of sodium and water handling in SHR. It is possible that this defect is located at the distal nephron, and is made apparent by the action of ANF on glomeruli via a cyclic GMP-induced vascular effect.
Mineralocorticoid escape during kallikrein inhibition
Authors: Overlack Axel , Bäcker-Kreutz Evita , Ressel Christa , Müller Hans-Michael , Kolloch Rainer , Stumpe Klaus-O.
Published: August 2015

1. Kinins have been considered to be involved in the escape from the sodium retaining effects of mineralocorticoids. In a metabolic study in rats, the importance of the kallikrein-kinin system for sodium and potassium excretion was evaluated by aprotinin-induced kallikrein inhibition under basal conditions and during DOCA administration.

2. Kallikrein inhibition was accompanied by a transient sodium retention. The escape from the sodium retaining effect of DOCA was not affected. However, the DOCA-induced potassium loss was enhanced.

3. Kallikrein inhibition decreased urinary prostaglandin (PG) E2 and prevented the DOCA-induced rise in PGE2. Plasma renin activity was stimulated after 10 days of aprotinin administration.

4. The kallikrein-kinin system is not an important mediator of the escape phenomenon but it may play a role in the regulation of sodium and potassium excretion.
The ferritin content of normoblasts and megaloblasts from human bone marrow
Authors: Hodgetts J. , Peters S. W. , Hoy T. G. , Jacobs A.
Published: August 2015

1. Erythroblasts were enriched from human bone marrow samples and fractionated on Percoll gradients according to maturity.

2. Heart-type and spleen-type ferritin was measured in each fraction by an immunoradiometric assay.

3. In normal marrow, heart-type ferritin content was higher in the early erythroblast fractions and fell with maturation. Spleen-type ferritin content showed no such consistent change.

4. Megaloblastic erythroblasts had a significantly higher ferritin content.
Effects of packed cell volume reduction on renal haemodynamics and the renin-angiotensin-aldosterone system in patients with secondary polycythaemia and hypoxic cor pulmonale
Authors: Wallis P. J. W. , Cunningham J. , Few J. D. , Newland A. C. , Empey D. W.
Published: August 2015

1. Polycythaemia was corrected by erythrapheresis in ten patients with hypoxic cor pulmonale who were stable on regular diuretic therapy. Renal haemodynamics, renal function and the renin-angiotensin-aldosterone system were assessed before and afterwards.

2. Before erythrapheresis effective renal plasma flow (ERPF) was reduced (63% predicted) but glomerular filtration rate (GFR) was preserved (88% predicted) by a rise in filtration fraction (FF) (138% predicted). A negative correlation existed between ERPF and packed cell volume (r = −0.723; P < 0.02) and also between ERPF and Paco2 (r = − 0.710; P < 0.05). Polycythaemia was sufficient to maintain renal oxygen delivery (97% predicted).

3. After erythrapheresis systemic blood pressure, blood volume and blood viscosity all decreased. ERPF increased by 18% (P < 0.02). FF fell by 11% (P < 0.05) and GFR was unchanged. Renal oxygen delivery diminished by 25% (P < 0.001).

4. Plasma renin activity was increased in five patients and plasma aldosterone increased in two patients before erythrapheresis. No sustained fall occurred in plasma renin activity or plasma aldosterone, possibly because the haemodynamic consequences of the procedure had opposing actions on renin secretion.

5. Although the reduction in FF would per se tend to enhance renal sodium and water excretion, a diuresis or natriuresis did not occur consistently.
Elevation of sodium levels in the cerebral ventricles of anaesthetized dogs triggers the release of an inhibitor of ouabain-sensitive sodium, potassium-ATPase into the circulation
Authors: Jandhyala Bhagavan S. , Ansari Ahmad F.
Published: August 2015

1. The present studies are designed to determine whether a ouabain-sensitive inhibitor of Na+, K+−stimulated ATPase is released into the circulation when the Na+ levels are elevated in the cerebral ventricles in pentobarbital anaesthetized dogs. Na+−pump activity was estimated in the plantar and dorsal branches of the lateral saphenous veins by using the 86Rb-uptake method.

2. Infusion of the cerebral ventricles with the artificial cerebrospinal fluid (CSF) containing normal Na+ (0.15 mol/l) for over 120 min resulted in significant increases in only ouabain-sensitive 86Rb-uptake. In contrast, when the ventricles were perfused with the CSF containing high Na+ (0.3 mol/l) for similar periods, there were significant reductions in the ouabain-sensitive as well as in ouabain-insensitive 86Rb-uptake by the blood vessels.

3. Similar blood vessels from a separate group of dogs were incubated for 120 min in the plasma samples collected from the above groups in which normal or hypertonic Na+ solutions were infused. The data showed that ouabain-sensitive 86Rb-uptake (but not the insensitive component) was significantly inhibited only in those vessels which were incubated in the plasma samples that were obtained at 120 min after perfusion of the cerebral ventricles with CSF containing high Na+ (0.3 mol/l).

4. These studies have provided direct evidence which would suggest that the elevation of Na+ levels in the cerebral ventricles would precipitate the release of an inhibitor of the ouabain-sensitive Na+−pump into the circulation, perhaps due to an activation of Na+−sensitive and/or osmo-sensitive sites in the circumventricular organs. It is hypothesized that this humoral substance may be the same ‘natriuretic hormone’ which is released after acute expansion of circulating blood volume.
The effect of sodium bicarbonate on the flow-dependency of urinary prostaglandin excretion in man
Authors: Haylor J. , Lote C. J. , Thewles A.
Published: August 2015

1. The influence of oral water loading on the excretion rate of prostaglandin (PG) E was investigated in healthy human subjects in a control study where the urine was acidic (pH 5.7) and after oral sodium bicarbonate, which made the urine mildly alkaline (pH 7.2). PGE was immediately extracted from urine and measured by a radioimmunoassay technique.

2. After sodium bicarbonate (5 g) the urinary PGE excretion rate was some three-fold higher (P < 0.01) than in the control study, in the absence of any significant difference in the urine flow (approximately 80 ml/h).

3. In the control study (urine pH 5.7) the urinary PGE excretion rate increased significantly (P < 0.01) as the urine flow rose in response to the oral fluid load. However, after sodium bicarbonate, PGE excretion did not alter after the fluid load despite a 10-fold increase in urine flow.

4. Since after bicarbonate administration PGE excretion is independent of urine flow, mildly alkaline urine may represent a condition under which renal PGE synthesis can be effectively assessed from measurements of urinary PGE excretion, in the presence of changes in urine flow.

5. In addition, the results are compatible with the hypothesis that, in man, PGE may be passively reabsorbed in the distal nephron, and a reduction in this reabsorption could contribute to or be responsible for the dependency of the excretion rate of PGE on urine flow.
Desensitization of platelet α2-adrenoceptors after short term infusions of adrenoceptor agonist in man
Authors: Jones C. R. , Giembcyz M. , Hamilton C. A. , Rodger I. W. , Whyte K. , Deighton N. , Elliott H. L. , Reid J. L.
Published: August 2015

1. The effect of intravenous infusion of catecholamines and related drugs on human platelet α2-adrenoceptor number and function was investgated.

2. Short (60–120 min) infusions of catecholamines with α2 agonist activity in vivo produced attenuation of the platelet responses to adrenaline in vitro. This desensitization was specific for the adrenaline induced aggregatory response.

3. The maximum number of [3H]yohimbine binding sites on platelets was not altered by adrenaline infusion.

4. The ability of adrenaline to reduce platelet cyclic AMP levels was significantly reduced after the infusions.

5. Acute infusions of α2-adrenoceptor agonists may alter the coupling of the platelet α2-adrenoceptor to adenylate cyclase.
Evaluation of an isotope washout technique to measure skin vascular resistance and skin perfusion pressure: influence of age, site and arterial surgery
Authors: Duncan Henry J. , Faris Irwin B.
Published: August 2015

1. A simplified isotope washout technique has been devised to calculate the skin perfusion pressure (SPP) and skin vascular resistance (SVR). This test is simple, requires inexpensive equipment and is well tolerated by patients.

2. SPP and SVR were calculated in 20 patients <30 years of age, 13 patients ≥.30 years of age and in 15 patients with peripheral vascular disease (PVD). With increasing age the SPP and SVR were increased. The SPP was similar to the mean arterial pressure in normal individuals but was decreased in patients with PVD. The SPP is a useful indicator of the severity of the PVD.

3. The SPP and SVR were higher in the calf than in the foot. This is probably related to the decrease in pressure in the distal arterial tree.

4. SPP was increased by 110% and skin blood now by 190% by arterial reconstructive surgery. This test may be of use in assessing the effectiveness of arterial surgery.
Increased chemiluminescence of polymorphonuclear leucocytes from patients with progressive systemic sclerosis
Authors: Kovacs Iren B. , Thomas R. H. Meyrick , Mackay A. R. , Rustin M. H. A. , Kirby J. D. T.
Published: August 2015

1. Chemiluminescence (CL) of whole blood and isolated polymorphonuclear leucocytes (PMN) from patients with systemic sclerosis (SS) and from age and sex matched controls was measured. CL was induced by the addition of particles (zymosan, latex beads), or phorbol myristate acetate (PMA) or chemotactic peptide (FMLP).

2. Whole blood CL (induced by PMA, zymosan or latex particles) was significantly greater in SS patients than in normal controls.

3. Isolated PMN CL (induced by PMA, FMLP or latex particles) was also significantly greater in the SS patients compared with controls.

4. Increased CL or PMN from patients with SS was mainly observed when luminol was used as amplifier (which detects hydrogen peroxide formation). In most cases, lucigenin-amplified CL of PMN from patients with SS (which detects the primary superoxide anion radical formation) did not differ from the controls.

5. Sera from patients with SS significantly increased both spontaneous and induced CL of normal PMN.

6. Enhanced excitability of PMN to phagocytosis-related stimuli may provide a mechanism for the (leucocyte-mediated) endothelial injury in SS.
The effect of cyclical hormonal changes on erythrocyte electrolyte transport mechanisms
Authors: Gallery Eileen D. M. , Bean Catherine , Grigg Roslyn , Saunders Douglas M.
Published: August 2015

1. Electrolyte transport characteristics were examined in erythrocytes from 13 normal men and from two groups of women: (i) taking combined oral contraceptive preparations (O/C, n = 10), and (ii) ovulatory women (non-O/C, n = 10) pre- and post-ovulation, at the same time intervals (days 7–10 and days 15–18) during a menstrual cycle.

2. With rubidium (86Rb+) used as a potassium analogue, co-transport (ouabain-resistant, fruse-mide-sensitive 86Rb+ influx) values were found to be lowest in non-O/C women (28 ± se 2.5 nmol h−1 10−9 cells) and highest in men (56 ± 5.7, P < 0.001), with results between the two in women taking O/C (42 ± 4.2, P < 0.05 vs men, P < 0.01 vs non-O/C). Passive 86Rb leak (frusemideand ouabain-resistant) was significantly lower in men (13 ± 1.6 nmol h−1 10−9 cells) than in both groups of women (non-O/C 29 ± 1.8, P < 0.001; O/C 25 ± 1.2, P < 0.001). There was no cyclical variation within either group of women.

3. Maximum ouabain binding (number of Na+,K+-ATPase units) was the same in all groups. Na+,K+-ATPase activity, as determined by ouabain-sensitive 86Rb influx, was the same in men and non-O/C groups, but was significantly suppressed in O/C compared with both men (P < 0.01) and non-O/C women (P < 0.05).

4. The differences found were not due to alterations in either progesterone or aldosterone, but could represent an androgenic effect in vivo of the 19-nortestosterone derivatives in combined oral contraceptive preparations.
Effects of acid-base disturbances on renal handling of magnesium in the dog
Authors: Wong Norman L. M. , Quamme Gary A. , Dirks John H.
Published: August 2015

1. Clearance and micropuncture studies were performed in four groups of acutely thyropara-thyroidectomized animals to study the effects of alkalosis and acidosis on the renal handling of magnesium.

2. Our results indicate that chronic metabolic acidosis reduces, whereas acute metabolic alkalosis enhances, magnesium reabsorption.

3. The site within the nephron where absorption of magnesium increases or decreases during acid-base disturbances was beyond the late proximal tubule.

4. Tubular fluid bicarbonate was also measured in these experiments, and the results indicated that magnesium reabsorption in the distal tubule correlated to bicarbonate delivery. However, whether this was a direct or an indirect effect of bicarbonate on magnesium transport could not be delineated.
Blood flow in skeletal muscle of tetraplegic man during postural changes
Authors: Andersen Erling Bo , Boesen Finn , Henriksen Ole , Sonne Michael
Published: August 2015

1. Relative changes in blood flow and vascular resistance in arm and leg muscle during head-up tilt at 45° were studied in eight patients with complete cervical spinal cord transection and in 13 healthy volunteers.

2. Muscle blood flow was measured by the local 133Xe washout method.

3. In forearm muscle kept at heart level blood flow remained constant in the tetraplegic patients during head-up tilt, in contrast to that seen in the normal subjects, where blood flow decreased by 30%. In the dependent leg muscle, head-up tilt caused a decrease in blood flow of 46% and 40% in the patients and normals, respectively. Abolition of the local veno-arteriolar axon reflex, by inducing local counter-pressure to prevent venous distension in the dependent leg muscle, reduced the decrease in blood flow to 24% and 23%, respectively. Thus, the vascular response to head-up tilt differed significantly in forearm muscle between the two groups, whereas no difference was seen in the leg muscle.

4. The absence of the vasoconstrictor response in forearm muscle indicates that postural sympathetic reflexes to this region depend on sympathetic reflexes integrated in centres located rostrally to the spinal cord. The results further suggest that local veno-arteriolar axon reflexes as well as spinal reflexes contribute to the observed vasoconstriction in the leg muscle.
Urogastrone–epidermal growth factor concentrations in prostatic fluid of normal individuals and patients with benign prostatic hypertrophy
Authors: Gregory H. , Willshire I. R. , Kavanagh J. P. , Blacklock N. J. , Chowdury S. , Richards R. C.
Published: August 2015

1. High concentrations (272 ± 33 ng/ml) of urogastrone-epidermal growth factor were measured in prostatic fluid from normal males by a specific radioimmunoassay.

2. 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 < 0.01).

3. The growth factor content of seminal fluid was accounted for by the contribution of prostatic fluid.

4. 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.
Release of adenosine and its metabolites from activated human leucocytes
Authors: Mann Jonathan S. , Renwick Andrew G. , Holgate Stephen T.
Published: August 2015

1. Human leucocytes whose adenine nucleotide pool was prelabelled with [3H]adenine were investigated for their capacity to release adenosine and its metabolites and histamine when activated with the calcium ionophore A23187, antiimmunoglobulin E and the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (f-MLP).

2. Sixty-nine per cent of the 3H-label assimilated by the cells was incorporated into their adenine nucleotide pool in the ratio adenosine 5′-phosphate (AMP):adenosine 5′-pyrophosphate (ADP):adenosine 5′-triphosphate (ATP), 3:1:1. Spontaneous release of label from leucocytes plateaued at 5 min at 22.1 ± 4.2% of the total radiolabel incorporated and mainly consisted of hypoxanthine, inosine and adenosine.

3. Activation of cells with the calcium ionophore A23187 (1.0 μmol/l) caused a net increase in [3H]purine release above baseline of 27.9 ± 4.6% accompanied by a net basophil histamine release of 46.6 ± 9.4%. A23187 (1.0–3.0 μmol/l) caused a parallel concentration-dependent release of labelled purines and histamine. Purified mononuclear cells and granulocytes exhibited a similar ionophore-dependent capacity to release [3H]purines.

4. The distribution of label did not significantly differ between supernatants of activated and non-activated cells. Preincubation of cells with dipyridamole (10μmol/l) and erythro-9-(2-hydroxy-3)-nonyladenine (EHNA) (10μmol/l) to inhibit uptake and catabolism of adenosine respectively, produced an increase in adenosine at the expense of hypoxanthine recovered from the supernatant of both ionophore-stimulated and resting cells.

5. Activation of leucocytes with f-MLP (1.0μmol/l) caused a net increase in release of basophil histamine, but was associated with only a transient net increase in release of [3H]purine in four of five experiments. Immunoglobulin E-dependent stimulation produced basophil histamine release in the absence of detectable [3H]purine release.

6. These data demonstrate that leucocytes can be stimulated to release adenosine and related nucleoside matabolites accompanying the release of basophil-derived histamine. As adenosine is a bronchoconstrictor in asthma and leucocyte infiltration of the airways is a characteristic feature of the disease, leucocyte-derived adenosine may contribute to the pathogenesis of airways obstruction.
Renal prostaglandins in cirrhosis of the liver
Authors: Guarner C. , Colina I. , Guarner F. , Corzo J. , Prieto J. , Vilardell F.
Published: August 2015

1. Urinary prostaglandin excretion was studied in 42 patients with liver cirrhosis and in nine control subjects on restricted sodium intake and on bed rest. Creatinine clearance (CCr), sodium excretion (UNaV), plasma renin activity (PRA) and plasma aldosterone were also evaluated.

2. Patients without ascites and ascitic patients without renal failure showed increased urinary excretion of immunoreactive 6-ketoprostaglandin F1α (i6-keto-PGF1α), prostaglandin E2 (iPGE2) and thromboxane B2 (iTXB2) when compared with controls, while immunoreactive PGF2α (iPGF2α) levels did not differ from those in the control group. Patients with functional renal failure (FRF) presented a significant reduction of vasodilator prostaglandins but urinary excretion of iTXB2 was higher than in controls.

3. On the whole, cirrhotic patients with higher urinary excretion of prostaglandins had normal or nearly normal PRA and aldosterone levels. i6-keto-PGF1α and iPGE2 inversely correlated with PRA and aldosterone.

4. The relationship between i6-ketoPGF1α and CCr was found to be highly significant in cirrhotic patients but not in the control group. On the other hand, iPGE2 significantly correlated with UNaV and with the fractional excretion of sodium (FENa).

5. We concluded that: (a) enhanced renal prostaglandin synthesis in cirrhosis, inversely related to PRA and aldosterone, may be dependent on volume status; and (b) preserved renal function in these patients is associated with the ability to synthesize prostacyclin and PGE2.
Differences in age-independent effects of blood pressure on baroreflex sensitivity between normal and hypertensive subjects
Authors: Shimada Kazuyuki , Kitazumi Tadao , Ogura Hisakazu , Sadakane Noriko , Ozawa Toshio
Published: August 2015

1. Inter-relationship between age, systolic blood pressure and baroreflex sensitivity index derived from the Valsalva manoeuvre was investigated in either combined or separated groups of normal and hypertensive subjects.

2. Both in the total population as a whole and in each blood pressure subgroup, the baroreflex sensitivity index was significantly inversely related to age and to systolic blood pressure. Furthermore, age was significantly related to systolic blood pressure except in the hypertensive group.

3. Partial correlation analysis showed that, in the total and hypertensive population, the baroreflex sensitivity index was significantly related to age and systolic blood pressure independently of each other variable. In the normal group, however, the baroreflex sensitivity index was not related to systolic blood pressure after adjusting for the effect of age, but remained significantly related to age independently of systolic blood pressure. The estimates of relative effects of the two variables on baroreflex sensitivity by multiple regression analysis were consistent with these results.

4. Thus a prevailing concept of the inhibitory effect of blood pressure on baroreflex function may be accurate exclusively in hypertensive patients, and baroreflex function appears to be more sensitive to age-related changes in this system than to those related to blood pressure level, particularly in non-hypertensive normal subjects.
Stimulus-induced release of endogenous catecholamines from human washed platelets
Authors: Smith C. C. T. , Wilson A. P. , Prichard B. N. C. , Betteridge D. J.
Published: August 2015

1. Using high-performance liquid chromatography with electrochemical detection, we have studied the release of endogenous catecholamines from washed platelets induced to aggregate by ADP and thrombin.

2. Washed platelets exhibit irreversible aggregation with 10 μmol/l ADP and 0.3 unit of thrombin/ml, extents of aggregation being 27% and 76% respectively.

3. ADP (10μmol/l) increased noradrenaline release to the medium by 20% and adrenaline by 28%. As observed with aggregation, 0.3 unit of thrombin/ml produced a more marked effect on release than ADP, noradrenaline and adrenaline being increased by 570% and 169% respectively.

4. Values for platelet noradrenaline content were found to mirror those for the release from platelets induced by thrombin.

5. A correlation was observed between catecholamine release and the concentration of thrombin present in incubations. These data reflect the changes observed with platelet aggregation.

6. This is the first study to determine catecholamine release from platelets by direct measurement. Local catecholamine release after platelet aggregation in vivo may have important consequences for tissue perfusion.
Effect of serum from patients with essential hypertension on sodium transport in normal leucocytes
Authors: Gray H. H. , Hilton P. J. , Richardson P. J.
Published: August 2015

1. This study has confirmed that serum from patients with essential hypertension inhibits sodium transport and elevates intracellular sodium in normal human leucocytes in vitro when compared with that of well matched normotensive controls.

2. The magnitude of this effect was positively correlated with the diastolic blood pressure of the hypertensive patient.

3. The degree of sodium transport inhibition conferred by the hypertensive's serum was correlated with the abnormal sodium transport in the hypertensive's own leucocytes.

4. These results confirm the presence of a serum inhibitor of sodium transport in essential hypertension. The relationship between the inhibitory effect and severity of hypertension argues that it may be of mechanistic importance.
Sympathetic nervous system and dysfunction of the lower urinary tract
Authors: George N. J. R. , Reading C.
Published: August 2015

Careful clinical and investigative protocols allow the identification of a homogeneous group of patients with prostatodynia or ‘anxious bladder syndrome’ (underactive detrusor function). Psychophysiological studies and urodynamic measurements in such patients demonstrate remarkably consistent results, which, whilst lending support to the hypothesis that the sympathetic nervous system may affect bladder and urethral function, do not offer objective proof that adrenergic mechanisms are directly responsible for the observed dysfunctional state.
Effect of guar on second-meal glucose tolerance in normal man
Authors: Trinick T. R. , Laker M. F. , Johnston D. G. , Keir M. , Buchanan K. D. , Alberti K. G. M. M.
Published: August 2015

1. Whole body glucose turnover and absorption of a 50 g glucose drink was studied in six healthy volunteers on two occasions, 4 h after a ‘breakfast’ of 50 g of glucose, mixed on one occasion with 20 g of guar gum.

2. Plasma glucose concentrations were significantly reduced with guar gum compared with those obtained without guar gum (P < 0.0001).

3. Whole body glucose turnover studied by an intravenous primed dose constant infusion technique using d-[3-3H]glucose showed no significant difference between the two groups: 353 ± 15 mmol with guar and 350 ± 9 mmol without guar.

4. Total oral glucose absorption, followed with a D-[1-14C]glucose tracer, was significantly decreased by guar treatment, being 219 ± 3 mmol with guar and 239 ± 5 mmol without guar (P < 0.05).

5. Serum insulin levels were lowered by guar treatment (P<0.05) while those of C-peptide, gastric inhibitory polypeptide, glucagon, Cortisol and pancreatic polypeptide did not differ significantly.

6. Blood lactate concentrations were raised in the guar treated group (P < 0.05) whereas pyruvate, alanine, glycerol and 3-hydroxybutyrate concentrations did not differ significantly.

7. These results support the suggestion that guar improves second-meal tolerance to glucose by decreasing absorption.
Cytoplasmic free [Ca2+] is not increased in the platelets of deoxycorticosterone–salt and spontaneously hypertensive rats
Authors: Murakawa Koh-Ichi , Kanayama Yoshiharu , Kohno Masakazu , Kawarabayashi Takahiko , Yasunari Kenichi , Takeda Tadanao , Hyono Atsushi
Published: August 2015

1. The cytoplasmic free calcium concentration ([Ca2+]i) in the platelets of spontaneously hypertensive rats (SHR), Wistar–Kyoto rats (WKY), deoxycorticosterone–salt hypertensive rats (DOC) and normotensive Sprague–Dawley rats (SD) was measured with the fluorescent dye, quin-2-tetra-acetoxymethyl ester.

2. No significant difference in platelet [Ca2+]i was found between SHR and WKY or between DOC and SD rats.

3. No correlations were found between systolic blood pressure and [Ca2+]i.

4. These results suggest that the elevation of platelet [Ca2+]i does not necessarily accompany hypertension in rats.
Selective effects of graft-versus-host reaction on disaccharidase expression by mouse jejunal enterocytes
Authors: Lund E. K. , Bruce M. G. , Smith M. W. , Ferguson A.
Published: August 2015

1. Graft-versus-host reaction (GvHR) was induced in neonatal mice to produce crypt hyperplasia with and without stunted villi. Lactase activity was measured along individual villi of control and GvHR mice using quantitative cytochemistry.

2. Lactase activity increased in control mice as enterocytes migrated over the lower part of the villus. This increase was followed by a period when lactase activity remained approximately constant.

3. Effects produced by GvHR on this normal profile of development included an extension of the distance on the villus over which enterocytes could continue to increase lactase activity, a reduction in the time needed for an enterocyte to express lactase activity at maximal rate, and an overall decrease in the maximal lactase activity expressed by mature enterocytes.

4. These effects have been quantified by fitting logistic curves to the experimental data.

5. Parallel biochemical analyses of intestinal homogenates showed sucrase, isomaltase, trehalase and maltase activities to increase markedly 7–8 days after the injection of parental spleen cells.

6. Attention is drawn to similarities between these results and steroid induced precocious development of intestinal function in neonatal mice.
Infused salbutamol accentuates acid-induced lung injury in the rat
Authors: Braude Stanley , Royston David
Published: August 2015

1. The effect in the rat of salbutamol infusion (1 μg min−1 kg−1) on acid-induced lung injury has been determined. Severity of lung injury was assessed by two techniques: the pulmonary clearance of 99mTc-diethylenetriaminepenta-acetate (99mTc-DTPA) and the lung wet/dry weight ratio, giving indices of alveolar epithelial permeability and transendothelial water filtration respectively.

2. Mean half-time of clearance of 99mTc-DTPA was increased significantly in rats who had intratracheal acid-induced injury and control (saline) intravenous infusion (19.4 ± 2.6 min) compared with non-acid-treated rats (98.1 ± 7.2) (P < 0.0001). However, those animals who had intratracheal acid injury and subsequent salbutamol intravenous infusion had significantly faster clearance (11.5 ± 1.9) than the acid and control infusion group (P < 0.05).

3. Gravimetric lung water in the acid-only rats (expressed as wet/dry weight ratio) was increased significantly (6.4 ± 0.3) compared with the non-acid-treated controls (5.4 ± 0.2) (P < 0.01). Acid-treated rats who had salbutamol infused had dramatically increased lung water (10.0 ± 0.6) (P < 0.001 vs acid and control infusion).

4. Intravenous salbutamol infusion itself produced no significant difference in the results for both techniques, compared with the non-acid-treated time-course controls.

5. Infused salbutamol accentuates acid-induced lung injury in the rat. Possible factors responsible for these findings include β2-adrenergic agonist mediated inhibition of hypoxic pulmonary vasoconstriction (HPV) and a predominant β1-adrenergic agonist inotropic effect of salbutamol with resultant rise in pulmonary artery pressure.
An improved approach for the determination of plasma [3H]noradrenaline kinetics using high-performance liquid chromatography
Authors: Howes L. G. , MacGilchrist A. , Hawksby C. , Sumner D. , Reid J. L.
Published: August 2015

1. An improved approach for the determination of plasma [3H]noradrenaline ([3H]NA) kinetics in man is described, incorporating the extraction of plasma [3H]catechols on alumina and separation of [3H]NA from [3H]dihydroxymetabolites by high-performance liquid chromatography (HPLC).

2. After a 30 min intravenous infusion, [3H]NA accounted for 57.2 ± 13.2% of the radioactivity recovered by the procedure, while the dihydroxymetabolites 3,4-[3H]dihydroxyphenylethylene glycol ([3H]DHPG) and 3,4-[3H]dihydroxymandelic acid ([3H]DOMA) accounted for 32.3 ± 11.5% and 4.9 ± 6.0% respectively. After 90 min of constant infusion the proportion due to [3H]NA fell to 44.4 ± 10.4%, while that due to [3H]DHPG rose to 45.9 ± 9.5% because of an increase in the amount of [3H]DHPG at the later time.

3. Plasma [3H]NA radioactivity rose rapidly during the constant infusion and usually reached a plateau by 30 min. However, in individual subjects large variations in plasma [3H]NA radioactivity occurred during the course of the infusion, implying rapid and variable changes in plasma [3H]NA clearance.

4. The inclusion of a step to separate [3H]NA from [3H]dihydroxymetabolites is necessary if the aim is to determine plasma [3H]NA kinetics, as a large proportion of the radioactivity recovered from plasma on alumina is due to the presence of these metabolites.
Humoral hypercalcaemia of malignancy: Report of two further patients with biochemical studies on tumour extracts
Authors: Seshadri M. S. , Mason R. S. , Cornish C. J. , Pryke A. M. , Posen S.
Published: August 2015

1. Tumour extracts from two patients with humoral hypercalcaemia of malignancy contained material which stimulated adenylate cyclase in chick renal membranes and in rat osteosarcoma cells.

2. Adenylate cyclase-stimulating activity in each system was inhibited by a specific parathyroid hormone (PTH) antagonist.

3. Studies in two HPLC systems suggested that the adenylate cyclase-stimulating factors extracted from these tumours differed from each other and from synthetic human parathyroid hormone 1–34.

4. The presence of similar PTH-like adenylate cyclase stimulating material(s) in oncogenic osteomalacia suggests that adenylate cyclase stimulating factor(s) may not be the direct or the sole cause of hypercalcaemia.
Muscle metabolism in patients with peripheral vascular disease investigated by 31P nuclear magnetic resonance spectroscopy
Authors: Hands L. J. , Bore P. J. , Galloway G. , Morris P. J. , Radda G. K.
Published: August 2015

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 31P 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.