bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiac Output Measured by Transthoracic Impedance Cardiography at Rest, during Exercise and at Various Lung Volumes
Authors: Edmunds A. T. , Godfrey S. , Tooley Marion
Published: August 2015

1. Cardiac output measured by transthoracic impedance cardiography has been compared with simultaneous measurements made by the indirect Fick CO2 rebreathing method in nine adults and 14 children. All were healthy normal volunteers. Sixty-six comparisons were made at rest and during steady exercise at work loads up to 100 W.

2. Impedance measurements of cardiac output were consistently higher than indirect Fick measurements of cardiac output, but after application of a correction factor related to packed cell volume there was close correlation between the results obtained by the two methods (r = 0·94).

3. The mean coefficient of variation of impedance measurements of cardiac output was 13% at rest and 5% during steady-state exercise.

4. Changes of lung volume due to breath holding or resulting from addition of an expiratory resistance did not affect the measurement of cardiac output by impedance.

5. Transthoracic impedance cardiography is a rapid, non-invasive technique for measurement of cardiac output. It requires very little active co-operation from the subject. The method would probably give reliable results for patients with respiratory illnesses such as acute asthma or bronchiolitis, during which changes of lung volume may be expected to occur.
Effects of Inhalation of β-Sympathomimetic and Atropine-Like Drugs on Airway Calibre in Normal Subjects
Authors: MacNee W. , Douglas N. J. , Sudlow M. F.
Published: August 2015

1. Bronchodilatation was produced in eight normal subjects by inhalation, on separate occasions, of the atropine-like drug ipratropium bromide (0·16 mg by pressurized inhaler; 1 mg nebulized) and the β-sympathomimetic salbutamol (0·8 mg by pressurized inhaler; 5 mg nebulized).

2. Mean specific airways conductance (sGaw) increased from a mean value of ·185 ± se 0·002 to 0·292 ± 0·023 s−1 kPa−1 after ipratropium bromide, and from 0·184 ± 0·020 to 0·303 ± 0·026 s−1 kPa−1 after salbutamol. These increases in sGaw were not significantly different from each other.

3. During both maximal and partial expiratory flow volume manoeuvres similar increases in flow rates were produced by each drug, at all lung volumes, from 40 to 20% of vital capacity.

4. Changes in maximal and partial flow volume curves after washout of lung air with helium/oxygen (4:1) were measured before and after each drug. Flow rates increased in all subjects and the percentage increase in maximum flow when helium was breathed was not significantly different, when repeated after each drug.

5. Thus our results suggest that salbutamol and ipratropium have similar sites of action, both affecting both large and small airways, and produce similar degrees of bronchodilatation. This is supported by our results after the helium/oxygen breathing, where the lack of change in density dependence of maximal flow suggests that there was no change in the distribution of airways resistance after the drugs.
Hyperoxaluria in Idiopathic Calcium Stone Disease: Further Evidence of Intestinal Hyperabsorption of Oxalate
Authors: Marangella M. , Fruttero B. , Bruno M. , Linari F.
Published: August 2015

1. Seventeen healthy controls and 63 patients with idiopathic calcium stone disease of the urinary tract were investigated for urinary calcium and oxalate excretion and for [14C]oxalate intestinal absorption.

2. Under comparable controlled dietary intake a significant increase in calcium excretion was found in patients with stone disease. Oxalate excretion and [14C]oxalate intestinal absorption were mildly but not significantly increased. When patients with stone disease were subdivided into normocalciuric and hypercalciuric subjects, oxalate excretion and [14C]oxalate absorption were significantly increased in the latter. There was a significant direct relationship between calcium excretion and both oxalate excretion and [14C]oxalate absorption.

3. [14C]Oxalate absorption increased significantly in 22 stone-formers when dietary calcium was changed from normal to low.

4. The kinetics of [14C]oxalate intestinal absorption showed that the main difference between normocalciuric and hypercalciuric subjects occurred within the first 6 h after the oxalate-labelled meal.

5. These results confirm that mild hyperoxaluria is a frequent feature of idiopathic calcium stone disease even when patients and controls are studied under controlled dietary conditions. Our data are consistent with the hypothesis that hyperoxaluria is secondary to calcium hyperabsorption and is upper intestinal in origin.
Regulation of Brain Renin: Evidence for an Independent Brain Renin
Authors: Dzau Victor J. , Sands Kenneth E.
Published: August 2015

1. We examined the effects of various physiological states on systemic and brain renin activities. Activation of the systemic renin-angiotensin system (RAS) by renal ischaemia, captopril or continuous renin infusions had no effect on whole brain or pituitary renin activities. Suppression of circulating renin by bilateral nephrectomy or antirenin antibody injection did not influence brain renin.

2. Brain or pituitary renin activities remained unchanged with various endocrine-metabolic disorders such as hypo- or hyper-thyroidism, diabetes and hypophysectomy.

3. Treatment with reserpine or propranolol resulted in significant decrease in brain and pituitary renin levels.

4. We conclude that brain renin activity appears to be generally independent of the systemic RAS. Inhibition of sympathetic activity, however, resulted in suppression of brain renin, suggesting a close interaction between the two systems.
Brain Angiotensin II Does Not Mediate the Cardiovascular Response to Cerebroventricular Administration of Hypertonic Sodium Chloride Solution in Dogs
Authors: Takishita Shuichi , Ferrario Carlos M.
Published: August 2015

1. A possible interaction between an osmotic stimulus and brain angiotensin II was studied in anaesthetized dogs by measuring the changes in arterial pressure, heart rate and renal sympathetic nerve activity during a brain ventricular injection of hypertonic NaCl solution before and after pretreatment with either captopril or [Sar1, Ile8]angiotensin II.

2. Mild pressor responses accompanied by a reflex decrease in renal sympathetic nerve activity were a characteristic before pretreatment, but after baroreceptor denervation the cardiovascular response to hypertonic NaCl solution doubled and the activity increased. These changes were prevented by intravenous pretreatment with hexamethonium chloride.

3. Brain ventricular injection of captopril slightly augmented pressor and tachycardia effects of hypertonic NaCl solution.

4. Blockade of central angiotensin II receptors with [Sar1, Ile8]angiotensin II was without effect.

5. It is concluded that central administration of hypertonic NaCl solution in baroreceptor-denervated dogs produces marked pressor responses due to increased sympathetic nerve activity via mechanisms not related to the brain renin-angiotensin system.
Interaction of Metoprolol, Propranolol and Atenolol with Cimetidine
Authors: Kirch W. , Spahn H. , Köhler H. , Mutschler E.
Published: August 2015

1. Pharmacokinetics of metoprolol, propranolol and atenolol were investigated in six healthy volunteers after 7 days of oral monotherapy with these drugs and after 7 days concurrent administration, with each of these β-adrenoceptor antagonists with cimetidine.

2. Cimetidine did not interact with atenolol, whereas mean peak plasma concentrations of metoprolol were increased by 70%, and those of propranolol by 95% with concurrent administration of cimetidine (P < 0.05).

3. The area under the plasma concentration-time curve for propranolol and metoprolol was similarly increased (P < 0.05).
Effect of Long-Term, Once-Daily Administration of Atenolol, Metoprolol, Pindolol and Slow-Release Propranolol on Ambulatory Blood Pressure and its Variability
Authors: Floras J. S. , Jones J. V. , Hassan M. O. , Sleight P.
Published: August 2015

1. Twenty-four-hour intra-arterial blood pressure recordings were made before and after chronic β-receptor blockade in 34 patients with essential hypertension.

2. Subjects were randomized in double blind fashion to either atenolol, metoprolol, pindolol or slow-release propranolol.

3. Drugs were administered in a once-daily variable dose regimen for a period of 3–8 months (mean 5.0 ± sd 1.4).

4. All four drugs reduced blood pressure significantly 24 h after the last dose but there were considerable differences in control when each intervening hour was assessed separately.

5. Not all β-receptor blockers in conventional formulations are equally effective as antihypertensive agents over 24 h when taken once daily.
Erythrocyte Sodium and Potassium in Patients with Hypokalaemia
Authors: Cumberbatch M. , Morgan D. B.
Published: August 2015

1. The erythrocyte content of sodium and of potassium were measured in 231 unselected patients with hypokalaemia, and together with net ouabain-sensitive sodium efflux in patients with severe hypokalaemia, before (20 patients) and during potassium repletion (14 patients).

2. The erythrocytes of the patients with hypokalaemia compared with control subjects had on average an increase in sodium content, a decrease in potassium content and a reduction in the rate constant of ouabain-sensitive sodium efflux. All three changes had a similar curvilinear relation to the concentration of potassium in plasma with relatively little change in the measured variable unless the plasma potassium was very low.

3. There was a similar curvilinear relation between the final sodium and potassium content of normal erythrocytes and the potassium concentration of the medium in which they were incubated for 48 h in vitro.

4. These results suggest that the changes in the sodium and potassium content of erythrocytes in hypokalaemia are due to a direct inhibiting effect of the hypokalaemia on the activity of the sodium pump.

5. In many patients with hypokalaemia of moderate degree the increase in erythrocyte sodium content was less than expected from the effect in vitro of a low extracellular potassium concentration. This finding suggests that a compensatory change, presumably an increase in the number of sodium pumps, is a common event even in moderate hypokalaemia.
Reversible Acid Activation of Amniotic Fluid Inactive Renin
Authors: Franks Robert C. , Bodola Francis , Renthal Robert D. , Hayashi Robert H.
Published: August 2015

1. Inactive renin was isolated from human amniotic fluid by chromatography with DEAE-cellulose, pepstatin-aminobutyl-agarose, octylagarose and Cibacron Blue F3GA columns.

2. Before and after isolation from amniotic fluid, inactive renin could be activated by incubation with pepsin and by dialysis to pH 3.3, and the acid activation could be reversed by subsequent incubation at pH 7.4 and 37°C.

3. Inactive renin was not activated by procedures expected to dissociate renin from an inhibitor.

4. The results suggest a pH-dependent conformational change as the mechanism of reversible acid activation of inactive renin in amniotic fluid.

5. There are chromatographic and activation similarities of inactive renin from human plasma, kidney and amniotic fluid.
Lactic Acidosis and the Cardiovascular System in the Dog
Authors: Arieff Allen I. , Gertz Edward W. , Park Robert , Leach Will , Lazarowitz Virginia C.
Published: August 2015

1. Lactic acidosis is a clinical syndrome characterized by metabolic acidaemia (pH < 7.25) and hyperlactaemia (lactate >5 mmol/l). Many patients with type B lactic acidosis have no evidence of tissue hypoxia or myocardial dysfunction when first evaluated. Although it is considered that cardiac dysfunction is secondary to the systemic effects of lactic acidosis, the reverse may sometimes be true. To evaluate this possibility, studies were carried out in 43 dogs consisting of a control group and three groups which had hyperlactataemia and metabolic acidaemia related to either: (1) phenformin infusion; (2) hepatectomy; (3) lactic acid infusion. Serial studies of cardiac function, as well as measurements of GFR (glomerular filtration rate) and hepatic portal vein (HPV) blood flow, were carried out.

2. in dogs infused with phenformin for 99 min, the arterial pH, lactate, bicarbonate, heart rate and mean blood pressure (BP) were normal. However, there was significant deterioration (P < 0.01) in several indices of cardiac function, including the peak positive dP/dt, cardiac output, LVEDP (left ventricular end-diastolic pressure) and percentage extraction of oxygen and lactate by the heart. After 3 h of phenformin, the blood lactate exceeded 5 mmol/l and there were further significant decrements (P < 0.01) in cardiac output, LVEDP and dP/dt, as well as BP and heart rate. in dogs subjected to hepatectomy, the decrement in cardiac output was similar to that with phenformin infusion. However, in animals infused with lactic acid, despite a similar blood pH and lactate, cardiac output was unaffected. Although percentage myocardial oxygen extraction declined in phenformin-infused animals, there was a concomitant increase in coronary sinus blood flow such that myocardial oxygen utilization was probably unaltered.

3. Thus, in certain types of experimental type B lactic acidosis, myocardial dysfunction may be a primary event, with other associated systemic manifestations being secondary.
The Use of 4-Aminobenzoic Acid as a Marker to Validate the Completeness of 24 H Urine Collections in Man
Authors: Bingham Sheila , Cummings J. H.
Published: August 2015

1. At the present time there is no method whereby the completeness of 24 h urine collections can be accurately assessed when clinical studies are undertaken. The suitability of 4-aminobenzoic acid (PAB) given with meals as a marker for completeness of urine collections was therefore investigated.

2. When a single dose of 80 mg of PAB was given to four volunteers 93% was recovered in the urine in 5 h.

3. Eight volunteers living in a calorimeter, where complete urine collection could be guaranteed, were given various doses of PAB divided up throughout the day. 88 ± 5% was excreted in the urine over a 24 h period. Urine excretion and oral dose were directly related.

4. Thirty-three reliable free-living volunteers eating their normal diet took 80 mg of PAB with meals (240 mg/day). Mean urine recovery over the 24 h period was 223 ± 9 mg, or 93 ± 4% of the administered dose. The range in individual recovery from maximum to minimum was 15%, compared with 75% for creatinine excretion per kg fat-free mass.

5. PAB is a safe marker of the completeness of 24 h urine collections. Any collection containing less than 205 out of 240 mg (85%) of PAB, given as 80 mg with each of three meals, is probably incomplete.
Studies on the Renin-Angiotensin System in a Kininogen-Deficient Individual
Authors: Wong Patrick Y. , Williams Gordon H. , Colman Robert W.
Published: August 2015

1. The physiological responses of the renin-angiotensin system were studied in an individual with kininogen deficiency (patient 1) with absent plasma bradykinin and markedly impaired prekallikrein conversion into kallikrein. After sodium depletion, patient 1 had a low plasma renin activity (1.4 pmol of ANG I h−1 ml−1) and a low angiotensin II concentration (36 pg/ml) compared with values in 11 normal individuals (4.0 ± 0.94 pmol of ANG I h−1 ml−1) and 63 ±6 pg/ml respectively).

2. Unlike normal individuals, in the kininogen-deficient subject there was no significant fall of renin activity or angiotensin II after dietary sodium repletion. Intravenous sodium repletion also failed to further decrease plasma renin activity or angiotensin II.

3. The usual two- to three-fold rise in plasma renin activity and angiotensin II observed in normal subjects on assumption of the upright posture after ingestion of 200 mg of sodium/day failed to occur in the kininogen-deficient individual.

4. These data in vivo are in agreement with observations in vitro that once plasma kallikrein forms it may be important in converting prorenin into renin. In the absence of kininogen, activation of prekallikrein to kallikrein is grossly defective, which may in part account for the diminished response of the renin-angiotensin system to changes in sodium balance and posture.
Adrenaline Secretion during Exercise
Authors: Warren J. B. , Dalton N. , Turner C. , Clark T. J. H. , Toseland P. A.
Published: August 2015

1. By studying six normal subjects during graduated treadmill exercise, we have confirmed that there is very little rise in venous plasma adrenaline levels during mild or moderate exercise.

2. During a second study, adrenaline was infused intravenously in six resting subjects at a rate of 0.025 μg min−1 kg−1. This elevated the basal plasma adrenaline level from 0.28 ± 0.04 nmol/l to 0.92 ± 0.16, 1.16 ± 0.20 and 1.28 ± 0.19 nmol/l at 3, 5 and 7 min after the start of the infusion.

3. The same adrenaline infusion was repeated in the same subjects 7 min after they started moderate exercise at a constant rate on a static exercise bicycle. Just before the start of the infusion, 7 min after the onset of exercise, plasma adrenaline had risen to 0.36 ± 0.07 nmol/l. This rose to 1.86 ± 0.30, 1.98 ± 0.26 and 2.19 ± 0.29 nmol/l at 3, 5 and 7 min after the start of this second infusion. Five minutes after the end of the infusion, while the subjects were still exercising, the mean level was 0.56 ± 0.04 nmol/l.

4. The venous plasma level of adrenaline is the result of a balance between the secretion of adrenaline by the adrenal medulla and the clearance of adrenaline from plasma. Our results suggest that the lack of any significant rise in plasma adrenaline during moderate exercise does not result from an accelerated clearance of adrenaline by exercising tissue. The clearance rate of adrenaline from plasma is reduced during exercise.

5. There is no significant increase in secretion by the adrenal medulla in response to the stimulus of mild or moderate exercise.
The Effect of Water Abstention on Milk Synthesis in Lactating Women
Authors: Prentice A. M. , Lamb W. H. , Prentice Ann , Coward W. A.
Published: August 2015

1. The effects of dehydration on mechanisms of water balance and milk synthesis were investigated in ten lactating Gambian women who were fasting during Ramadan. Ten non-pregnant, non-lactating women acted as controls. Fasting consisted of total water abstention from 05.00 hours to 19.30 hours and was accompanied by high insensible water losses.

2. Lactating women lost 7.6% of their total body water between 07.00 hours and 19.00 hours. Control subjects lost significantly less.

3. Plasma indices of dehydration (osmolality, sodium, uric acid) showed a greater rise in the lactating women than in the control subjects over the period of fasting. However, the 19.00 hours values remained in the normal range obtained on non-Ramadan days.

4. During Ramadan the lactating women restricted their urinary output to a lesser degree than the controls, and for much of the day their urine was also less concentrated. The lactating women appeared to have adapted by superhydrating themselves overnight. This resulted in very low urine concentrations (osmolality, sodium, urea, creatinine) in morning samples. Urine concentrations approached, but did not exceed, non-Ramadan levels by late afternoon.

5. The daily water turnover of 6.4 litres in the lactating women was 2 litres greater than in the controls. This difference was much greater than that required for milk synthesis (500 ml) and may represent a further protective mechanism.

6. Fasting caused changes in milk osmolality, lactose, sodium and potassium concentrations indicative of a marked disturbance of milk synthesis. The results suggested that the normally tight junctions between the mammary secretory cells had become permeable to small ions and formed a paracellular pathway.
The Mechanism of Action of Guar Gum in Improving Glucose Tolerance in Man
Authors: Blackburn N. A. , Redfern J. S. , Jarjis H. , Holgate A. M. , Hanning I. , Scarpello J. H. B. , Johnson I. T. , Read N. W.
Published: August 2015

1. Experiments were carried out in human volunteers to investigate the mechanism by which guar gum improves glucose tolerance.

2. Guar reduced both plasma glucose and insulin responses to an oral glucose load, and delayed gastric emptying. However, there was no correlation between changes in individual blood glucose responses and changes in gastric emptying rates induced by guar.

3. With a steady-state perfusion technique, glucose absorption was found to be significantly reduced during perfusion of the jejunum with solutions containing guar, but returned to control values during subsequent guar-free perfusions.

4. Preperfusing the intestine with guar did not affect electrical measurements of unstirred layer thickness in the human jejunum in vivo..

5. Experiments in vitro established that glucose diffusion out of a guar/glucose mixture was delayed under conditions of constant stirring.

6. We conclude that guar improves glucose tolerance predominantly by reducing glucose absorption in the small intestine. It probably does this by inhibiting the effects of intestinal motility on fluid convection.
Polymorphisms in the 5′-Flanking Region of the Insulin Gene and Non-Insulin-Dependent Diabetes
Authors: Hitman G. A. , Jowett N. I. , Williams L. G. , Humphries S. , Winter R. M. , Galton D. J.
Published: August 2015

1. DNA insertions in the 5′-flanking region of the insulin gene have been studied by Southern-blot-hybridization techniques using a cloned gene probe in 159 unrelated Caucasians.

2. Subjects homozygous for a large DNA insertion at this locus were found to have a higher risk of concurrence of non-insulin-dependent diabetes (NIDD) than controls (P < 0.01).

3. Analysis of a single large NIDD pedigree (n = 67 in four generations; 11 diabetic subjects) showed no linkage between the size of DNA inserts and diabetes (Lod score = −5.7), suggesting a separate diabetogenic locus (or loci) in this family.
A non-Invasive Technique for Continuous Monitoring of Left Ventricular Function Using a New Solid State Mercuric Iodide Radiation Detector
Authors: Lahiri A. , Crawley J. C. W. , Jones R. I. , Bowles M. J. , Raftery E. B.
Published: August 2015

1. A miniature solid-state mercuric iodide (HgI2) nuclear probe detector has been developed in conjunction with a computerized nuclear probe (Nuclear Stethoscope) to enable continuous noninvasive monitoring of left ventricular function using 99Tc-labelled equilibrium blood pool techniques.

2. Left ventricular ejection fraction was measured in 54 patients undergoing radionuclide angiography with a gamma-camera and with the Nuclear Stethoscope and a good correlation was obtained between both techniques (r = 0.94, n = 54, P < 0.001).

3. The prototype mercuric iodide detector was compared with the sodium iodide detector of the Nuclear Stethoscope and a study in 41 consecutive patients demonstrated a good correlation for the measurement of ejection fraction, ejection rate, peak filling rate and time to peak filling rate (r = 0.94, 0.89, 0.90 and 0.78 respectively).

4. It may be possible to adapt the mercuric iodide detector for continuous non-invasive monitoring of left ventricular performance in critically ill patients and during physiological or pharmacological interventions.
Urinary pH as a determinant of prostaglandin E2 excretion by the conscious rat
Authors: Haylor J. , Lote C. J. , Thewles A.
Published: August 2015

1. The urinary excretion of prostaglandin E2 (PGE2) was measured in conscious rats under conditions which produced either acid or alkaline urine, but similar change in fluid and solute excretion.

2. Oral isotonic saline increased both urine flow and sodium excretion but did not alter urinary PGE2 output (which remained constant at 80 pmol/3 h per rat) or urine pH (6.2).

3. When the urine was made alkaline (pH 7.8) by oral sodium bicarbonate or carbonate, urinary PGE2 was approximately 3-fold greater (P<0.00l) than the control (pH6.2). The urine flow and sodium output were also increased.

4. When the urine was made acidic (pH 5.7) by oral ammonium chloride, urinary PGE, excretion was reduced (P<0.01) to approximately half the control output. The urine flow and sodium output increased.

5. Within a group of 12 rats receiving oral isotonic saline a positive linear correlation coefficient (P<0.002) was established between urine pH and PGE2 excretion.

6. The results indicate that urine pH may be a determinant of PGE2 excretion in unrestrained, conscious rats. It seems likely that this effect of pH is mediated by a change in the passive reabsorption of PGE, in the distal nephron, although alternative explanations such as altered tubular secretion or synthesis cannot be categorically excluded.
Response to indomethacin and hydrochlorothiazide in nephrogenic diabetes insipidus
Authors: Monnens L. , Jonkman A. , Thomas C.
Published: August 2015

1. Four boys with classical nephrogenic diabetes insipidus have been treated by indomethacin, by hydrochlorothiazide, and by the combination of indomethacin and hydrochlorothiazide.

2. Hydrochlorothiazide treatment was slightly more effective than indomethacin treatment in reducing the urine volume and increasing the urine osrnolality.

3. The combination of indomethacin and hydrochlorothiazide appeared to be additive and especially helpful in infants and young children before the autonomy of drinking.
Association of Secondary Hyperparathyroidism with Red Cell Survival in Chronic Haemodialysis Patients
Authors: Saltissi D. , Carter G. D.
Published: August 2015

1. 51Cr red cell mass (RCM), 51Cr red cell survival (RCS) and plasma parathyroid hormone (PTH) levels were measured in 27 stable chronic haemodialysis patients with a variable degree of clinical secondary hyperparathyroidism. Included were five patients who had had total parathyroidectomy.

2. The results showed a strong negative correlation between PTH and RCS (r = −0.67, P<0.001) and a positive correlation between RCS and RCM (r = + 0.53, P<0.005). However, the negative correlation between PTH and RCM was weak (r = −0.45, P<0.02). When the 13 patients with normal PTH levels (mean 0.18 ± 0.12 μg/l) were compared with the 14 patients with raised levels (mean 1.35 ± 0.71 μg/l), there was a marked difference in RCS (P<0.005) but no difference in RCM.
Altered Neuropeptide Concentrations in Spontaneously Hypertensive Rats: Cause or Consequence?
Authors: Gaida W. , Lang R. E. , Kraft K. , Unger Th. , Ganten D.
Published: August 2015

1. Changes in brain neuropeptide content in spontaneously hypertensive rats may be primarily related to the development of hypertension or may be secondary consequences of it.

2. We have measured brain concentrations of β-endorphin, Leu-enkephalin, arginine vasopressin (AVP) and oxytocin (OXT) in stroke-prone spontaneously hypertensive rats (SHRSP) and in age-matched normotensive Wistar Kyoto (WKY) controls, as well as in SHRSP with normalized blood pressure by chronic treatment with clonidine. Opioid peptide contents were measured in 12-, 18- and 24-week-old rats. β-Endorphin was measured in the neuro-intermediate and anterior lobes of the pituitary, the hypothalamus, midbrain and brain stem; Leu-enkephalin in the neuro-intermediate lobe of the pituitary, hypothalamus, mid-brain, brain stem, as well as in the spinal cord and adrenal glands. AVP and OXT were measured in the neuro-intermediate lobe of the pituitary, hypothalamus, brain stem and spinal cord.

3. β-Endorphin in the neuro-intermediate lobe of the pituitary was significantly higher in 12- and 18-week-old SHRSP. Adrenal gland Leu-enkephalin was lower in SHRSP as compared with the WKY.

4. OXT and AVP contents were markedly reduced in all brain regions of SHRSP except the neuro-intermediate lobe of the pituitary, where no significant changes were found.

5. In no case did long-term antihypertensive treatment with clonidine reverse the altered peptide content in the SHRSP.

6. We conclude that alterations in brain neuropeptide content in SHRSP are not secondary to hypertension. The blood pressure lowering activity of clonidine appears not to depend on major alterations of peptide concentrations. A genetic defect in the synthesis of adrenal enkephalins and hypothalamic OXT and AVP seems likely from these studies.
The contribution of the renin-angiotensin system to limb vasoregulation in patients with heart failure: observations during orthostasis and α-adrenergic blockade
Authors: Creager Mark A. , Faxon David P. , Rockwell Susan M. , Gavras Haralambos , Coffman Jay D.
Published: August 2015

1. In patients with congestive heart failure, both the sympathetic nervous system and renin-angiotensin system are often stimulated. In order to assess the contribution of the renin-angiotensin system to limb vascular resistance, the forearm haemodynamic response to captopril was studied in 13 patients with heart failure.

2. Seven subjects were studied while supine and during 60° head-up tilt. To eliminate α-adrenergic effects, six additional patients with heart failure were pretreated with intra-arterial phentolamine and then given captopril. Venous occlusion plethysmography was used to determine forearm blood flew and forearm vascular resistance.

3. Tilt did not significantly increase pretreatment plasma renin activity or plasma noradrenaline concentration, nor did it decrease forearm blood flow. Furthermore, captopril did not alter forearm vascular resistance during supine or upright posture. During the phentolamine infusion, however, captopril reduced forearm vascular resistance by 19% (P < 0.05).

4. Despite increased plasma renin activity, captopril did not cause forearm vasodilatation during supine or upright posture in these patients with heart failure. When the contribution of the sympathetic nervous system was eliminated, captopril decreased forearm vascular resistance. Therefore, in patients with congestive heart failure, the sympathetic nervous system is important in limb vasoregulation, and the contribution of the renin-angiotensin system is apparent only after α-adrenergic blockade.
The mechanisms of action of noradrenaline on ouabain-sensitive rubidium uptake in guinea-pig myocardium
Authors: Wanless Richard B. , Noble Mark I. M. , Drake-Holland Angela J. D.
Published: August 2015

1. The mechanism by which noradrenaline stimulates ouabain-sensitive rubidium uptake in guinea-pig myocardial tissue has been studied.

2. The stimulatory action of low concentrations of noradrenaline was reversed by high doses of propranolol (10−5 mol/l) in atrial tissue, but was not reversed by α- or β-, or combined α- and β-adrenoceptor antagonists in ventricular tissue.

3. Rubidium uptake was also found to increase with increasing extracellular potassium concentration ([K]o). The percentage values of stimulation by noradrenaline decreased with increasing [K]o.

4. Noradrenaline had no effect on the rate of ATP splitting by an isolated membrane preparation of Na,K-ATPase.

5. It is proposed that noradrenaline stimulates active cation transport by either (a) an effect secondary to increased passive efflux of K ions, or (b) an action at a novel adrenergic receptor, distinct from the ATPase enzyme itself.
Effects of erythrapheresis on pulmonary haemodynamics and oxygen transport in patients with secondary polycythaemia and cor pulmonale
Authors: Wallis P. J. W. , Skehan J. D. , Newland A. C. , Wedzicha J. A. , Mills P. G. , Empey D. W.
Published: August 2015

1. Reducing packed cell volume has been advocated as a therapeutic procedure in patients with polycythaemia secondary to hypoxic cor pulmonale. The aim of this investigation was to evaluate the effects of this manoeuvre on resting pulmonary haemodynamics and tissue oxygenation in 12 such patients.

2. The subjects were studied whilst they were breathing air (n = 12), after breathing 35% oxygen for 30 min (n= 11) and breathing air 30 min after isovolaemic reduction in packed cell volume, from 0.61 ±0.02 to 0.50 ±0.02 (mean ± sem), by erythrapheresis (n = 12). Initial values for the group were: Pao2 6.5 ± 0.3 kPa; red cell mass 152 + 12% predicted; mean pulmonary artery pressure (PAP) 41 ± 3 mmHg; cardiac index 3.1 ± 0.3 1 min−1 m−2.

3. Breathing 35% oxygen reduced PAP by 3.1 ± 1.0 mmHg (P < 0.02), cardiac index by 0.28 ± 0.121 min−1 m−2 (P < 0.05) and right ventricular stroke work by 0.05 ± 0.01 J (P < 0.01). Systemic vascular resistance was unchanged. Systemic oxygen transport increased and peripheral oxygen consumption was unaltered.

4. Erythrapheresis reduced blood viscosity at shear rates 23 s−1 and 230 s−1. PAP fell by 2.4 ± 1.1 mmHg (P < 0.05) and cardiac index increased by 0.32 ± 0.09 1 mm−1 m−2 (P < 0.01), but right ventricular stroke work was unchanged. Systemic vascular resistance was reduced by 25 ± 7 kPa s l−1 (P < 0.01). Systemic oxygen transport decreased but peripheral oxygen consumption was unchanged.

5. These results confirm the effect of oxygen in reducing PAP in patients with hypoxic cor pulmonale. Reducing blood viscosity by reversing polycythaemia also improved pulmonary haemodynamics but unlike oxygen its effects were not confined to the pulmonary circulation.

6. Although erythrapheresis reduced the oxygen carrying capacity of the blood, tissue oxygenation was not impaired at rest. However, oxygen transport during exercise was not assessed in this study.
Chronic effects of oral sulindac on renal haemodynamics and hormones in subjects with chronic renal disease
Authors: Swainson Charles P. , Griffiths Peter , Watson Michael L.
Published: August 2015

1. The effects of oral sulindac, 600 mg daily, on renal function and plasma hormones were studied in eight subjects with chronic renal failure.

2. Renal function and plasma hormones were measured before drug administration and then after taking sulindac for 28 days.

3. Effective renal plasma flow was reduced in all subjects after 28 days but the glomerular filtration rate did not change.

4. Plasma renin activity, potassium and aldosterone concentrations and urinary sodium excretion did not change but urinary prostaglandin E2 excretion fell significantly.

5. Sulindac may be a relatively renal-sparing drug in its effects on the hormonal control of glomerular function.
The contribution of the autonomic nervous system, the renin-angiotensin system and vasopressin to the maintenance of arterial blood pressure in adrenalectomized Wistar rats
Authors: Gardiner S. M. , Bennett T.
Published: August 2015

1. Factors contributing to the maintenance of resting arterial blood pressure in sham-operated and adrenalectomized rats were assessed 14 weeks after operation; some animals were given 1% NaCl to drink throughout, and some animals were given sodium-free water instead of 1% NaCl for 2 days before the experiment.

2. Inhibition of the renin-angiotensin (ANG) system (with captopril) and of the cardiovascular actions of vasopressin [with 1-(β-mercapto-β,β-cyclopentamethylenepropionic acid), 8-d-arginine vasopressin (d(CH2)5DAVP)] had no hypotensive effects in sham-operated rats under any conditions, but antagonism of nicotinic ganglionic transmission (with pentolinium) caused a prompt fall in blood pressure. During combined administration of captopril, d(CH2)5DAVP and pentolinium to sham-operated rats, there was no significant recovery of blood pressure.

3. Adrenalectomized rats drinking 1% NaCl showed a marked hypotension and tachycardia in response to captopril, but d(CH2)5DAVP had little effect, whether administered before or after captopril. Addition of pentolinium rendered these animals more hypotensive man the sham-operated rats.

4. Adrenalectomized rats drinking sodium-free water for 2 days were hypotensive and blood pressures were lowered further by d(CH2)5DAVP or captopril under these conditions; there was no accompanying tachycardia.

5. The results indicate that, in chronically adrenalectomized rats drinking 1% NaCl, blood pressure is maintained by autonomic nervous and renin-ANG systems with no discernible contribution from the peripheral cardiovascular actions of vasopressin. However, the latter contribute importantly to the support of blood pressure when the adrenalectomized rats are rendered hypovolemic and hypotensive by substitution of sodium-free water to drink.
Inhaled smoke volume, puffing indices and carbon monoxide uptake in asymptomatic cigarette smokers
Authors: Woodman G. , Newman S. P. , Pavia D. , Clarke S. W.
Published: August 2015

1. Nine asymptomatic smokers each smoked one cigarette of their usual brand on four separate occasions.

2. The inhaled smoke volume was measured by tracing the smoke with the inert gas 81Krm. Puffing indices were recorded by using an electronic smoking analyser and flowhead/cigarette holder. The expired air carbon monoxide concentration was measured immediately before and within 5 min of finishing smoking.

3. The inhaled smoke percentage (total inhaled smoke volume/total puff volume) averaged 46% to 85% in different subjects.

4. Neither the mean inhaled smoke volume per puff nor the total inhaled smoke volume per cigarette was significantly correlated with any of the puffing indices.

5. Smokers took significantly smaller and shorter puffs, left longer between puffs and inhaled less smoke as the cigarette was smoked (P < 0.01), although the proportion of the puff which was subsequently inhaled did not change significantly.

6. There was no significant intra-subject difference in any index from one visit to another.
Rod mediated retinal dysfunction in cats with zinc depletion: Comparison with taurine depletion
Authors: Jacobson S. G. , Meadows N. J. , Keeling P. W. N. , Mitchell W. D. , Thompson R. P. H.
Published: August 2015

1. Cats fed for 4 months with a diet with less than 7 p.p.m. zinc developed tissue zinc depletion, as judged by reduced muscle zinc content.

2. Dark adapted electroretinogram (ERG) thresholds became elevated in zinc depleted cats. Electroretinograms and muscle zinc levels were reversed by zinc supplementation.

3. Rod ERG to suprathreshold stimuli became reduced in b-wave amplitude in cats with zinc depletion, but suprathreshold cone ERG were unchanged.

4. The ERG changes in zinc depleted cats were unlike those in cats fed on a taurine depleted diet.
The osmotic thresholds for thirst and vasopressin release are similar in healthy man
Authors: Thompson C. J. , Bland J. , Burd J. , Baylis P. H.
Published: August 2015

1. The relationship between thirst perception and plasma osmolality was studied during hypertonic and physiological saline infusion in ten healthy volunteers.

2. Thirst perception was quantified using a linear visual analogue scale which volunteers marked at intervals during the infusion periods.

3. Infusion of hypertonic saline caused a steady rise in plasma osmolality together with a progressive linear increase in thirst perception and also plasma arginine vasopressin. No significant changes in thirst, plasma osmolality or plasma arginine vasopressin occurred during infusion of physiological saline.

4. Linear regression analysis of the results defined the functions. Thirst (cm) = 0.3 (plasma osmolality −281) (r = + 0.92, P < 0.001) and plasma arginine vasopressin (pmol/l) = 0.4 (plasma osmolality −285) (r = + 0.96, P < 0.001). The osmolar threshold for thirst onset thus defined (281 mosmol/kg) was much lower than in previous studies and similar to the theoretical osmolar threshold for vasopressin release (285 mosmol/kg).

5. We conclude that thirst perception rises in a progressive fashion throughout a wide range of plasma osmolality and that the osmolar threshold for thirst onset is similar to the theoretical osmolar threshold for vasopressin release.

6. The results are compatible with the concept of either a single osmoreceptor subserving both thirst and vasopressin release, or two osmoreceptors sharing similar functional characteristics.
Effect of dietary sodium chloride and posture on plasma immunoreactive atrial natriuretic peptide concentrations in man
Authors: Solomon L. R. , Atherton J. C. , Bobinski H. , Green R.
Published: August 2015

1. The effect of changes of dietary sodium chloride intake and posture on plasma atrial natriuretic peptide concentration and renal function was studied in 11 normal human volunteers.

2. Plasma atrial natriuretic peptide concentration was higher in the upright posture on a high than it was on a medium or low salt diet. On the medium and high but not on the low salt diet the concentration increased significantly on adoption of the supine posture.

3. Creatinine, sodium, lithium and fractional lithium clearances, fractional distal sodium excretion and total distal water and sodium reabsorption, which were estimated by the lithium clearance technique, were significantly higher on the high than on the low salt diet. The medium salt intake gave intermediate values.

4. Heart rate while upright was significantly higher on the low than on either the medium or the high salt diets. Systolic blood pressure was unaffected by salt intake. Diastolic blood pressure in the supine position was significantly higher on the low than on the medium or high salt diets.

5. Both plasma noradrenaline concentrations and plasma renin activity were significantly higher on the low than on the high salt diet. Values on the medium salt intake were intermediate. Plasma concentrations of both hormones were higher in the upright than in the supine posture on all three salt intakes.

6. The data are consistent with the hypothesis that atrial natriuretic peptide contributes to the cardiovascular and renal adjustments to changes in dietary sodium chloride, and the possible role of the peptide is discussed.
Loss of spontaneous variability of fingertip anastomotic blood flow in diabetic autonomic neuropathy
Authors: Corcoran J. S. , Yudkin J. S.
Published: August 2015

1. We have employed a thermal clearance probe to study fingertip blood flow, which comprises predominantly arteriovenous anastomotic flow.

2. In non-diabetic subjects there was a marked variability in resting fingertip blood flow which was of similar magnitude to that in diabetic subjects without autonomic neuropathy.

3. In 20 diabetic subjects with increasing severity of autonomic neuropathy there was a reduction of spontaneous variability in flow (r= 0.59, P < 0.001), which was not related to differences in basal flow, in skin thickness or in age.

4. There was no relationship between maximal flow and severity of autonomic neuropathy (r= 0.08), although basal flow was decreased in subjects with moderate, but not those with severe, autonomic neuropathy (P < 0.01 and P > 0.4 compared with controls).

5. Our failure to find an increase in basal fingertip flow in autonomic neuropathy could imply that spontaneous variability of anastomic flow is lost before increased arteriovenous shunting becomes apparent, but it could result from the indirect heating employed in the study causing vasodilatation in subjects without neuropathy.
Arterial oxygen saturation and breathlessness in patients with chronic obstructive airways disease
Authors: Lane R. , Cockcroft A. , Adams L. , Guz A.
Published: August 2015

1. Nine patients with chronic obstructive airways disease performed a 6 min self-paced walk (breathing air) on a treadmill and then identical (but operator-controlled) treadmill walks breathing either air or supplemental oxygen sufficient to just prevent arterial oxygen desaturation during the exercise.

2. During the exercises, ventilation was recorded and patients recorded their sensation of breathlessness on a visual analogue scale (VAS) every 30 s.

3. Breathing supplemental oxygen produced a small fall in mean exercise ventilation and a large and consistent reduction in mean exercise breathlessness. In seven patients the VAS scores were higher on air than with supplemental oxygen, at similar levels of ventilation. An analysis of co-variance, to control for reduction in ventilation, showed a decrease in mean breathlessness when breathing supplemental oxygen, significant at the 8% level.

4. The reduction in breathlessness produced by preventing exercise desaturation cannot be explained by the decrease in ventilation. This suggests that hypoxia may be a stimulus for breathlessness. The mechanism is unknown.
Bile acid binding to dietary casein: A study in vitro and in vivo
Authors: Lanzini A. , Fitzpatrick W. J. F. , Pigozzi M. G. , Northfield T. C.
Published: August 2015

1. Studies were carried out in vitro using an ultracentrifugation method to quantify bile acid binding to the different components of a Lundh test meal, and to determine what factors influence bile acid binding to one of the components (casein). We validated the ultracentrifugation method by showing good agreement with the equilibrium dialysis method. Studies were carried out in vivo on jejunal aspirate from 10 ileal resection patients in order to determine whether bile acid binding to casein could be demonstrated, and whether this influenced aqueous-phase bile acid and fatty acid concentrations.

2. In vitro, the Lundh test meal was found to adsorb bile acid. The protein content of the meal (casein) alone accounted for this binding, which was abolished by use of casein hydrolysate. The binding to casein was a saturable process. Both binding affinity and binding capacity were significantly greater for taurocholate at pH 4.5 than at pH 6.5, and for dihydroxylated than for trihydroxylated bile acid, suggesting that hydrophobic bonding was involved.

3. In vivo, jejunal samples aspirated at pH > 6 from 10 ileal resection patients showed 25% binding of bile acid to protein. On substitution of amino acids for casein, mean binding was reduced to 16% (P < 0.05), residual binding being attributed to endogenous protein. This was associated with an increase in fatty acid solubilization from 28% to 60% (P < 0.025).

4. These findings suggest that protein binding may have a critical effect on aqueous-phase bile acid and fatty acid concentrations in certain patients with a reduced total bile acid concentration as in ileectomy steatorrhoea, and in patients with defective lipolysis as in pancreatic insufficiency. This finding may provide an additional rationale for the use of elemental diets in severely ill patients with steatorrhoea.
Effect of changes in local skin temperature on postural vasoconstriction in man
Authors: Hassan Ahmad A. K. , Tooke J. E.
Published: August 2015

1. The effects of locally induced alterations in skin temperature on the postural changes in skin blood flow of the foot were assessed in 38 healthy subjects in a constant-temperature environment (22 ± 0.5°C, mean ± sd).

2. Moderate local cooling and warming of the foot (26–36°C) was induced by blowing cold or hot air. Higher ranges of temperature (38–44°C) were achieved by a thermostatically controlled disc heater.

3. Skin blood flow was measured before and during each change in local skin temperature using a laser Doppler flowmeter with the foot maintained at heart level, and placed passively 50 cm below the heart. Blood flow was measured in two skin areas: (i) the dorsum of the foot, where arteriovenous anastomoses are absent, and (ii) the pulp of the big toe, where these anastomoses are relatively numerous.

4. It was found that within the physiological temperature range of 26–36°C the normal postural fall in foot skin blood flow was preserved, whereas it was markedly attenuated or totally abolished at higher temperatures (38–44°C). The pattern of response was quite similar in areas having or lacking arteriovenous anastomoses.

5. It is suggested that the failure of postural vasoconstriction observed at the higher skin temperatures might contribute to some of the problems of cardiovascular adaptations seen in a hot environment.