bluuebunny/crossref_metadata_2025 huggingface dataset:
Airway Function in Healthy Subjects and Patients with Left Heart Disease
Authors: Collins J. V. , Clark T. J. H. , Brown D. J.
Published: August 2015

1. In forty non-smoking healthy subjects and seventy-two patients with left heart diseases measurements were made of the volume expired in the first second of a forced expiration (FEV1) and the total volume expired in a forced expiration (FVC) before and after inhalation of salbutamol. Before and after salbutamol the healthy subjects and patients also inhaled maximally an inspirate, the first part of which contained 133Xe and, during controlled expiration, the radioactivity of the expirate was measured and plotted against its volume. The resulting curves were divided into phases of different slope by eye, the point at which phase 3 changed to phase 4 being nominated the closing volume.

2. In forty non-smoking healthy subjects inhalation of salbutamol was followed by significant increase in FEV1 but FVC and closing volume did not change.

3. Change in posture from seated erect to supine in thirty of these healthy subjects was accompanied by significant reduction in FEV1 and FVC and as closing volume was not significantly different in the two positions the ratio closing volume/vital capacity was increased with recumbency.

4. In seventy-two patients with left heart diseases without a history of cough or wheeze, FEV1, FVC, closing volume and the ratio closing volume/vital capacity were significantly different from values in the healthy subjects. There was no significant difference between non-smokers and ex-smokers amongst the patients.

5. Significant increase in FEV1, FVC and reduction in closing volume and the ratio closing volume/vital capacity followed inhalation of salbutamol in patients with heart diseases but the values remained significantly different from those recorded in the healthy subjects.

6. In twenty patients with heart diseases, FEV1 and FVC were reduced by change in posture from seated erect to supine but the ratio closing volume/vital capacity and the regression with age of this ratio were not significantly changed by change in position.

7. In patients with heart diseases the ratio closing volume/vital capacity was significantly correlated with severity of breathlessness and length of symptom-history but not with left ventricular end-diastolic or pulmonary vein wedge pressures.
Leg Blood Flow and Muscle Metabolism in Occlusive Arterial Disease of the Leg before and after Reconstructive Surgery
Authors: Pernow B. , Saltin B. , Wahren J. , Cronestrand R. , Ekeström S.
Published: August 2015

1. Leg blood flow, uptake of oxygen and glucose and release of lactate by the leg and changes in intramuscular concentrations of metabolites were studied at rest and during exercise of increasing work loads in thirteen patients with occlusive disease of the iliac or superficial femoral arteries.

2. Leg blood flow (dye-dilution technique) and oxygen uptake during exercise were low and levelled with increasing work load. Considerable increases were noted in muscle lactate concentration and in the net release of lactate from the exercising leg. Muscle content (needle-biopsy technique) of ATP and creatine phosphate decreased during exercise, with an almost complete depletion of creatine phosphate in three patients. The decrease in muscle glycogen during work did not differ significantly from that of control subjects.

3. Repeated exercise after reconstructive surgery showed a considerable improvement in physical working capacity. Leg blood flow and oxygen uptake during exercise were significantly higher than before surgery and increased linearly in relation to work intensity. The decrease in creatine phosphate and lactate concentration of the thigh muscle during exercise was less pronounced and the release of lactate was lower than before vascular reconstruction.

4. It is suggested that the onset of the severe muscle symptoms during exercise in patients with occlusive arterial disease of the leg may be related to a low concentration of ATP and creatine phosphate in the affected muscles.
Epitaxial Relationships in Urolithiasis: The Calcium Oxalate Monohydrate—Hydroxyapatite System
Authors: Meyer J. L. , Bergert J. H. , Smith L. H.
Published: August 2015

Chemical kinetic data, complemented with scanning electron-microscope observations of the crystalline phase, show that seed crystals of hydroxyapatite have the ability to induce the growth of calcium oxalate monohydrate crystals epitaxially from a metastable supersaturated solution of calcium oxalate. The rate of growth of calcium oxalate crystals is dependent on the surface area of the seed material and follows a second-order rate law. It is suggested that there may be a causal relationship between the occurrence of apatite crystals in the urinary tract and the formation of both ‘pure’ and mixed urinary stones containing calcium oxalate. Under similar experimental conditions, however, seed crystals of calcium oxalate monohydrate appeared unable to induce epitaxially the growth of calcium phosphate crystals from a supersaturated calcium phosphate solution, indicating the absence of an epitaxial relationship between calcium oxalate monohydrate and the initially precipitating calcium phosphate phase(s).
Anaerobic Glycolysis in Normal Human Erythrocytes Incubated in Vitro with Sodium Salicylate
Authors: Worathumrong N. , Grimes A. J.
Published: August 2015

1. Some effects of sodium salicylate upon anaerobic glycolysis have been studied in normal human erythrocytes incubated for up to 6 h at 37°C in autologous sera.

2. Both glucose consumption and lactate production were stimulated by concentrations of salicylate up to 60 mmol/l but at the highest concentration used (90 mmol/l) an initial stimulus was followed by inhibition of glycolysis.

3. Losses occurred of adenosine 5′-triphosphate (ATP), adenosine 5′-diphosphate (ADP) and adenosine 5′-phosphate (AMP) at higher concentrations of salicylate and there was a concomitant increase of inorganic phosphate.

4. Other phosphate esters underwent concentration changes at higher concentrations of salicylate that reflected inadequate concentrations of ATP for glycolysis.

5. The rates of sodium efflux from, and potassium influx into, erythrocytes were unaffected by the presence of salicylate at concentrations sufficient to stimulate glycolysis.
The Release of Renal Prostaglandins during Saline Infusion in Normal and Hypertensive Subjects
Authors: Papanicolaou N. , Safar M. , Hornych A. , Fontaliran F. , Weiss Y. , Bariety J. , Milliez P.
Published: August 2015

1. Renal venous prostaglandin concentrations (PGA, PGE and PGF) were determined, together with renal plasma flow, urinary output and blood pressure changes, before and after infusion of sodium chloride solution (saline) in four normotensive and three hypertensive subjects.

2. No changes in blood pressure and in glomerular filtration rate were observed.

3. Saline infusion induced a significant increase in renal venous PGA and PGE, and also in total and non-cortical renal plasma flow and urinary output. There was an insignificant increase in renal venous PGF.

4. These findings show that prostaglandin release after saline infusion is associated with changes in renal blood flow and suggest that the natriuretic and diuretic effect of saline could be the result of prostaglandin release.
The Effect of Frusemide on Water and Electrolyte Absorption from the Human Jejunum
Authors: MacKenzie J. F. , Cochran K. M. , Russell R. I.
Published: August 2015

1. Frusemide, in a dose of 120 nmol (40 mg) administered intravenously, significantly reduced the absorption of water and electrolytes from the human jejunum, a double-lumen perfusion system with proximal occluding balloons being used. Net secretion of water and electrolytes occurred in some subjects.

2. No significant change in water and electrolyte absorption was observed with 60 nmol (20 mg) of frusemide.

3. These findings may explain the diarrhoea which may be induced by frusemide in some patients.
Effect of Liver Failure on the Cerebral Circulatory and Metabolic Responses to Hypoxia in the Goat
Authors: Stanley N. N. , Cherniack N. S.
Published: August 2015

1. Six unanaesthetized goats were used to evaluate the effect of liver failure on the hypoxic responsiveness of cerebral blood flow. The animals breathed air and several different hypoxic gas mixtures enriched with sufficient CO2 to maintain an isocapnic state. The cerebral metabolic rate for O2 (CMRo2) was also measured in four of these goats.

2. In baseline studies there was a linear relationship between cerebral blood flow and arterial O2 saturation (Sa,o2) measured at different levels of isocapnic hypoxia. The slopes of the cerebral blood flow/Sa,o2 response lines were used to quantify the response of cerebral blood flow to hypoxia. In the healthy goat, CMRo2 was not depressed by hypoxia until the O2 tension (Po2) in arterial and cerebral venous blood had fallen below critical threshold values of approximately 3·2 and 2·2 kPa (24 and 16 mmHg) respectively.

3. Liver failure was accompanied by a fall in cerebral blood flow and CMRo2. There was also a depression in the response of cerebral blood flow to hypoxia and a disproportionate reduction of cerebral O2 delivery in hypoxia. CMRo2 was further reduced at arterial and cerebral venous Po2 values, which were much higher than the critical threshold values for producing hypoxic CMRo2 depression in health.

4. It is concluded that the brain becomes more vulnerable to the adverse effects of hypoxia during liver failure. This may be of practical importance in the management of patients with arterial hypoxaemia or other complications (e.g. anaemia or shock), which may reduce cerebral oxygen delivery.
Evidence for Both Luminal and Systemic Factors in the Control of Rat Intestinal Epithelial Replacement
Authors: Clarke R. M.
Published: August 2015

1. Isolation of a self-emptying sac of rat small intestine in vivo halved the cell production rate in the crypts of Lieberkühn as measured by colchicine blockade.

2. Starvation for 48 h of rats with isolated intestinal sacs caused a further halving of cell production rate in the sac.

3. Infusion of distilled water into isolated intestinal sacs for 72 h caused a similar degree of stimulation of cell production in sacs in fed and starved rats, suggesting that the fall in cell production rate on starving a rat bearing an isolated sac is not due to the non-availability of the substances required for cell synthesis.

4. The possible contribution of innervation of the gut, and of systemic hormonal influences, on intestinal epithelial replacement is discussed.
A Simple Method of Measuring Breath Hydrogen in Carbohydrate Malabsorption by End-Expiratory Sampling
Authors: Metz G. , Gassull M. A. , Leeds A. R. , Blendis L. M. , Jenkins D. J. A.
Published: August 2015

1. A simple method is described for measuring the hydrogen concentration in alveolar air by end-expiratory sampling, by using a modified Haldane—Priestley tube and gas chromatography. Hydrogen was generated in vivo by ingestion of the non-absorbable sugar lactulose.

2. Alveolar hydrogen concentration showed a highly significant correlation with hydrogen production measured either by a rebreathing technique or by a total collection procedure.

3. The coefficient of variation of the end-expiratory method, assessed by comparing sixty-one paired results, was 11·6%. The coefficient of variation in ten measurements in one subject at 1 min intervals was 17·6%.
The Intracellular pH of Human Leucocytes in Response to Acid—Base Changes in Vitro
Authors: Levin G. E. , Collinson P. , Baron D. N.
Published: August 2015

1. Viable human leucocytes were isolated from venous blood and suspended in artificial media. Intracellular pH measurements were made by the dimethyloxazolidinedione technique in conditions simulating ‘respiratory’ or ‘metabolic’ acid-base disturbances.

2. Normal intracellular pH was 7·11 ± 0·02 (mean ± 2 sd) at an extracellular Pco2 of 5·8 kPa and a bicarbonate concentration of 25 mmol/l.

3. ‘Respiratory’ and ‘metabolic’ acidosis caused little change in pH1 although increases in Pco2 led to relatively greater falls in pH1 than did reduction in external bicarbonate concentration.

4. ‘Respiratory’ and ‘metabolic’ alkalosis caused similar and relatively greater increases in the pH1 when compared with the response to an external acidosis.
Analytical Subcellular Fractionation Studies on Rat Liver and on Isolated Jejunal Enterocytes with Special Reference to the Separation of Lysosomes, Peroxisomes and Mitochondria
Authors: Peters T. J. , Shio H.
Published: August 2015

1. Enterocytes were isolated from rat jejunum and characterized morphologically.

2. Attempts to separate the enterocyte subcellular organelles, characterized by their marker enzymes, with isopycnic centrifugation were unsuccessful but good separation of peroxisomes, lysosomes and mitochondria was achieved by sedimentation through a shallow sucrose density gradient with a superimposed inverse gradient of low-molecular-weight dextran.

3. The properties and enzyme activities of the principal subcellular organelles in rat liver cells and enterocytes were compared.
The Ventilatory Response in Severe Metabolic Acidosis
Authors: Fulop M.
Published: August 2015

1. The ventilatory response to severe metabolic acidosis was studied by measuring arterial blood carbon dioxide tension and pH in sixty-seven patients with blood pH < 7·10, none of whom had hypercapnia, pulmonary oedema, or chronic pulmonary insufficiency. The results were compared with those previously found in patients with uncomplicated diabetic ketoacidosis.

2. By that comparison, fifty-two of the sixty-seven patients with blood pH < 7·10 were judged to have ‘appropriate hypocapnia’, and fifteen had ‘submaximal hypocapnia’. Thirteen of the latter fifteen had circulatory failure and/or acute hypoxia, and seven of nine in whom it was measured had plasma lactate >9 mmol/l.

3. Hyperventilation was therefore usually well sustained in these patients with severe metabolic acidosis, except in most of those with acute tissue hypoxia. The latter may have had insufficient time to achieve maximum hyperventilation in response to their acidosis, or perhaps their submaximal hypercapnia presaged imminent failure of the hyperventilatory response.
Disappearance of 125I-Labelled and Unlabelled Insulins from Blood in Normal and Injured Rats
Authors: Frayn K. N.
Published: August 2015

1. The disappearance from blood of either 125I-labelled bovine insulin or unlabelled rat insulin after a single intravenous injection has been studied in rats.

2. The disappearance of the labelled insulin was slower than that of native insulin.

3. Ether anaesthesia produced a significant impairment, and bilateral nephrectomy a very marked impairment, of disappearance of the labelled insulin, suggesting that changes in the removal of this tracer may nevertheless parallel changes in the metabolism of native insulin.

4. Simultaneous intravenous injection of unlabelled bovine insulin (1 unit/kg) did not affect disappearance of the labelled insulin.

5. A 20% full-thickness scald injury, produced 2 h previously, had no significant effect on disappearance of the labelled insulin, either with or without the simultaneous administration of unlabelled bovine insulin.

6. The disappearance of unlabelled rat insulin from plasma was also similar in control and scalded rats.

7. It was concluded that the half-life of plasma insulin in the rat, as estimated by either of the techniques used, is not significantly affected by this severe non-haemorrhagic injury.
Turnover of Plasma Glucose and Free Fatty Acids in Patients on the First Day after Myocardial Infarction
Authors: Nimmo I. A. , Smith R. H. , Dolder M. A. , Oliver M. F.
Published: August 2015

1. The turnover of plasma glucose and free fatty acids was measured in ten patients within 24 h of the onset of symptoms of acute myocardial infarction and in two with symptoms of acute myocardial ischaemia. The measurements were repeated in seven of the patients 12–40 weeks after the acute episode.

2. Both for the patients with acute myocardial infarction alone and for all the individuals studied the turnover of glucose increased with plasma glucose concentration but was not related to the turnover of free fatty acids or the plasma concentrations of free fatty acids, insulin or total catecholamines. There was no obvious difference in the nature of the glucose turnover—concentration relationship between the patients with acute myocardial infarction, with acute myocardial ischaemia and on re-examination.

3. For all the individuals studied the turnover of free fatty acids increased with the concentration of these but was not related to the turnover of glucose or the plasma concentrations of glucose, insulin or total catecholamines. There was no obvious difference in the nature of the free fatty acids turnover—concentration relationship between the patients with acute myocardial infarction, with acute myocardial ischaemia and on re-examination.
The Porphyrinogenic Effects of Kryptopyrrole in the Rat and the Occurrence of Urinary Kryptopyrrole in Human Hereditary Hepatic Porphyria
Authors: Brodie M. J. , Graham D. J. M. , Thompson G. G. , Moore M. R. , Goldberg A.
Published: August 2015

1. Kryptopyrrole (2,4-dimethyl-3-ethyl pyrrole) was shown to elevate the urinary porphyrin excretion and the hepatic content of porphyrins in the rat. The simultaneous administration of δ-aminolaevulinic acid increased these effects.

2. Kryptopyrrole was present in the urine of patients with hereditary hepatic porphyria, in attack and in remission, but not in those with latent porphyria.
Effect of Diphosphonates on Adenosine 3′:5′-Cyclic Monophosphate in Mouse Calvaria after Stimulation by Parathyroid Hormone in vitro
Authors: Gebauer U. , Russell R. G. G. , Touabi M. , Fleisch H.
Published: August 2015

1. The diphosphonates, disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) and disodium dichloromethylene diphosphonate (Cl2MDP), inhibit bone resorption in animals and in explanted bone in tissue culture. The possibility that these effects might be due to inhibition of skeletal adenylate cyclase has been studied.

2. EHDP and Cl2MDP, added for 30 mm to the incubation medium at concentrations known to inhibit bone resorption, had no effect on basal content of adenosine 3′:5′-cyclic monophosphate (cyclic AMP) of mouse calvaria incubated in vitro, nor did they inhibit the rise in cyclic AMP induced by bovine parathyroid hormone.

3. Pretreatment of mice for 3 days with Cl2MDP also had no effect on cyclic AMP under basal conditions or after incubation of explanted calvaria with parathyroid hormone in vitro. EHDP under similar conditions slightly inhibited the increase induced by parathyroid hormone but had no effect on basal concentrations of cyclic AMP.

4. It is suggested that the inhibition of adenylate cyclase is not an essential feature of the reduction of bone resorption by diphosphonates, which may act by direct inhibitory effects on the dissolution of hydroxyapatite and perhaps by other unidentified effects on bone cells.
Effects of Prednisolone on the Small Intestinal Mucosa of the Rat
Authors: Batt R. M. , Peters T. J.
Published: August 2015

1. The effects in rats of an oral pharmacological dose of prednisolone on mucosal function, enzymology, lysosomal membrane fragility, morphology and cell kinetics have been examined in proximal jejunum and distal ileum.

2. The maximum absorptive capacity for galactose was significantly greater in both the jejunum and the ileum of the steroid-treated animals. This was due to an increase in carrier-mediated transport in the individual enterocytes and not to a change in the cell population. The Michaelis constant for galactose was not significantly altered by prednisolone.

3. Activities of brush-border and mitochondrial enzymes and of RNA were increased in isolated enterocyte preparations from the jejunum and ileum of the steroid-treated group.

4. Lysosomal membrane fragility was unaltered in the prednisolone-treated group.

5. Morphometrical observations confirmed that the size of the enterocyte population was unaltered by prednisolone. Studies on cell kinetics indicate that the effects of prednisolone are due to a direct action on the enterocyte and not secondary to changes in migration rate.
Plasma Growth Hormone Concentrations in Huntington's Chorea
Authors: Phillipson O. T. , Bird E. D.
Published: August 2015

1. Growth hormone secretion was assessed in nine control subjects and nine patients with Huntington's chorea.

2. Early-morning fasting plasma samples from patients with Huntington's chorea contained abnormally high concentrations of growth hormone.

3. The suppression of growth hormone after oral glucose in choreic patients, unlike the control subjects, occurred at irregular intervals after the glucose was given and was followed, again at irregular intervals, by an exaggerated rebound phase.

4. The response to intravenous insulin was not markedly abnormal in choreic patients. However, there was a significant increase in the rate of rise of growth hormone concentration in the first half an hour after the insulin injection when compared with control subjects.
Differential Effects of Asp1-Angiotensin II and Sar1-Angiotensin II on Vascular and Adrenal Receptors in the Dog
Authors: Bravo E. L. , Khosla M. C. , Bumpus F. M.
Published: August 2015

1. Adrenocorticotrophic hormone-suppressed, bilaterally nephrectomized male mongrel dogs (n = 12) were infused with Sar1-angiotensin II and Asp1-angiotensin II, the naturally occurring octapeptide.

2. Sar1-angiotensin II was found to be almost twice as potent as Asp1-angiotensin II in elevating blood pressure but its aldosterone-stimulating activity was not higher than that of the naturally occurring peptide.

3. A specific competitive antagonist of angiotensin II, Sar1-Ile8-angiotensin II, blocked the pressor but not the aldosterone-stimulating activity of Sar1-angiotensin II.

4. These results suggest functional differences in receptors for angiotensin II in vascular smooth muscle and in adrenal cortex.
The Forced Expiratory Time as a Measure of Small Airway Resistance
Authors: Burki N. K. , Dent Mary C.
Published: August 2015

1. In five subjects, ten consecutive forced expiratory spirograms were recorded on each of 6 different days and the total forced expiratory time (FET) on each spirogram was measured. The mean overall coefficient of variation of the FET was 11·3% and of the ratio forced vital capacity (FVC)/FET was 8%.

2. Twenty-two subjects with probable small (<2 mm diameter) airway dysfunction as manifested by a reduced (<75% predicted) maximum mid-expiratory flow (MMEF) in the middle 50% of the FVC with normal FVC and FEV1 (>80% predicted) were studied before and after bronchodilatation. There was no significant correlation between change in FET and change in MMEF (r = 0·36, P > 0·01), but between change in MMEF (ΔMMEF) and change in FVC/FET (ΔFVC/FET) there was a positive correlation (r = 0·78, P < 0·001).

3. In six of these twenty-two subjects, the ΔFVC/FET and ΔMMEF on bronchodilatation correlated well with the change in residual volume (ΔRV), but neither measurement correlated well with the change in the ‘closing volume' measurement expressed as the ratio of phase 4/VC(%). The ΔFET did not correlate well with either ΔRV or Δ[phase 4/VC(%)].

4. In eighty-one selected normal subjects (FVC, FEV, and MMEF all >80% predicted) there was better correlation of age with the FVC/FET (r = −0·676) than with the FET (r = +0·43); both correlations were significant (P < 0·001).

5. These results do not support the use of the FET as a suitable test of small airway function; however, the mean flow rate expressed as FVC/FET may, in the presence of a normal FEV1/FVC ratio, be an adequate test of small airway function.
Reversible Resistance to the Renal Action of Parathyroid Hormone in Man
Authors: Tomlinson S. , Hendy G. N. , Pemberton D. M. , O'Riordan J. L. H.
Published: August 2015

1. Normal subjects showed a highly reproducible, rapid increase in plasma adenosine 3′:5′-cyclic monophosphate (cyclic AMP) after an intravenous injection of 200 MRC units of highly purified bovine parathyroid hormone.

2. No significant increase in plasma cyclic AMP was observed after administration of bovine parathyroid hormone to patients with severe chronic renal failure.

3. Even when renal function was not impaired, some patients with primary hyperparathyroidism, who had high concentrations of endogenous parathyroid hormone, showed resistance to bovine parathyroid hormone and when this was injected intravenously it caused only a small increase in plasma cyclic AMP. This resistance was reversible since there was marked improvement in the response after parathyroidectomy, when endogenous parathyroid hormone concentration had fallen.

4. It was possible to reproduce this resistance to the hormone by intravenous infusion of bovine parathyroid hormone into normal subjects. When the hormone (1000 MRC units) was infused over 2 h, after an initial increase there was a progressive decline in plasma cyclic AMP concentration and a fall in urinary cyclic AMP excretion. The response to a standard test stimulus (200 MRC units of bovine parathyroid hormone given as a rapid intravenous injection) was examined at intervals after 1000 units of bovine parathyroid hormone had been infused. Initially, the response was severely impaired; at 4 h, partial recovery had occurred and, 24 h after the infusion, recovery of the response was complete. The resistance was therefore reversible. Infusion of the amino-terminal peptide, fragment 1–34, gave the same effect as infusion of intact hormone. Region-specific assays for the hormone were used to show that the concentration of immuno-assayable hormone remained high during the infusions.

5. The mechanism of this reversible resistance to parathyroid hormone remains to be elucidated; it seems unlikely that circulating hormone fragments could account for the prolonged impairment in the responsiveness to the intact hormone. It is possible that alteration in the formation, intracellular degradation or, perhaps, release of cyclic AMP from the cells, is the cause. Changes in the characteristics of the hormone receptor sites might also explain the phenomenon.
Stimulated Flow of Pancreatic and Biliary Secretions after Intestinal Exposure to Cholera Toxin
Authors: Freiman I. , Melmed R. N.
Published: August 2015

1. Duodenojejunal intestinal loops in rats were perfused with cholera toxin and the pancreatic and biliary secretory responses studied.

2. Intraluminal cholera toxin induced a significant flow of pancreatic and biliary ñuid and sustained protein (enzyme) secretion in pancreatic juice, in addition to the expected stimulation of mucosal secretion.

3. Intravenously injected cholera toxin failed to elicit a secretory flow from the pancreas and biliary tract.

4. The time-course of the enhanced secretory flow from pancreas and biliary tract after intraluminal cholera toxin corresponds closely to the secretion of intestinal fluid.

5. The results of these studies provide evidence of sustained stimulation of pancreatic and biliary secretions after mucosal exposure to cholera toxin. These observations support the suggestion that secretion from the pancreas and liver may significantly contribute to the total intestinal secretion in cholera.
Effect of Posture on Renal Lithium Clearance
Authors: Smith D. F. , Shimizu M.
Published: August 2015

1. Renal lithium clearance in healthy men was elevated while the subject was reclining, decreased upon standing and increased upon lying down during 45–60 min tests.

2. Parallel changes in renal clearance of creatinine, sodium and potassium, and urine flow rate occurred in response to the changes in posture.

3. The findings demonstrate for the first time that posture is a factor that can influence lithium excretion. Control of posture during lithium excretion tests is recommended.
A Method for Measurement of Angiotensin II in Tissues and its Application to Rat Kidney
Authors: Mendelsohn F. A. O.
Published: August 2015

1. A method for extraction, partial purification and radioimmunoassay of angiotensin II in tissues and application of the method to the kidneys of sodium-deficient rats are described.

2. Angiotensin in acid—ethanol extracts of kidney were adsorbed on to a cation-exchange resin, eluted and further purified with an immobilized angiotensin II antiserum, before radioimmunoassay.

3. Thin-layer chromatography was used, in some experiments, to separate fmol amounts of angiotensin II from its immunoreactive peptide fragments before radioimmunoassay.

4. Angiotensin II-immunoreactive material isolated from rat kidney resembled angiotensin II in many of its physicochemical properties and chromatographic mobility.

5. The concentration of immunoreactive material in kidney greatly exceeded that which could be accounted for by trapped blood and suggests that the peptide may have a local role in the organ.
Measurement of Liver Blood Flow by Means of a Single Injection of Bromosulphthalein, without Hepatic Venous Catheterization
Authors: Clarkson M. J. , Hardy-Smith Anne , Richards T. G.
Published: August 2015

1. A method is described for the measurement of liver blood flow without hepatic venous catheterization by the injection of a single dose of bromosulphthalein and the analysis of the graph of the plasma disappearance of the indicator.

2. The rationale of the method was tested in three systems which covered a wide range of flow rates. The first system was a physical model with a haemodialyser in which the calculated flow could be compared with the flow measured directly. The second was in anaesthetized dogs, in which the calculated flow was compared with that measured by continuous infusion and hepatic venous catheterization, based on the Fick principle. The third system was in unanaesthetized turkeys, in which metabolism of bromosulphthalein does not occur. The calculated flow was compared with the flow measured simultaneously by the uptake of colloidal particles by the Kupffer cells.

3. In all three systems the correspondence between the two methods of measuring liver blood flow was good, the differences between them being not statistically significant.

4. The method has been applied to measurements of liver blood flow in man and animals and gives results comparable with those reported by other workers.
Comparison of Renal Blood Flow and Transit Times Measured by Means of 99mTc-Labelled Erythrocytes and Indocyanine Green in Humans with Normal and Diseased Kidneys
Authors: Reubi F. C. , Vorburger C. , Pfeiffer Gertrud , Golder S.
Published: August 2015

1. In nineteen patients with normal or diseased kidneys, renal blood flow, transit times and vascular volume were determined by means of an indicator-dilution method. Two different indicators, plasma-bound Indocyanine Green (IG) and 99mTc-labelled erythrocytes, were used simultaneously.

2. Comparison of the results indicates that IG slightly overestimates renal blood flow, appearance time, mean transit time and vascular volume, as the erythrocyte/IG ratios averaged 0·972, 0·903, 0·93 and 0·921 respectively. Overestimation of the mean transit time was less apparent when it was prolonged. In patients with reduced renal function, the average blood flow values obtained with the two indicators were in good agreement.

3. It is unlikely that axial streaming of erythrocytes accounts for their shorter mean transit time, because the individual erythrocyte/IG mean transit time ratios were independent of the rate of blood flow and the peripheral packed cell volume.

4. Since the erythrocyte/IG mean transit time ratios correlated significantly with the erythrocyte/IG ratios for appearance time and renal blood flow, the common mechanism leading to a depression of all erythrocyte/IG ratios is presumably extravascular circulation and delayed recovery of a small fraction of IG.
Kinetics of Hepatic Uptake of Unconjugated Bilirubin
Authors: Paumgartner G. , Reichen J.
Published: August 2015

1. The uptake of bilirubin was studied in the perfused rat liver by a multiple-indicator dilution technique employing the three-compartment model of Goresky.

2. The kinetics of hepatic bilirubin uptake could be described by the Michaelis—Menten equation.

3. The maximal uptake velocity (Vmax.) and the apparent half-saturation constant (Km) were 4·4 ± 0·5 nmol s−1 g−1 of liver and 58 ±16 nmol/g of liver respectively, indicating that the hepatic uptake system for bilirubin under normal conditions is operating far below saturation.

4. Sodium taurocholate did not compete with bilirubin for hepatic uptake.

5. These findings are consistent with the concept that carrier-mediated transport is responsible for hepatocellular uptake of bilirubin and that bilirubin and bile acids enter the hepatocyte via separate pathways.
Plasma Enteroglucagon and Plasma Volume Change after Gastric Surgery
Authors: Thomson J. P. S. , Bloom S. R.
Published: August 2015

1. The changes in plasma enteroglucagon concentration and plasma volume were measured after oral glucose in sixteen subjects before and forty-eight subjects after operative treatment for benign duodenal ulceration. Truncal vagotomy with a drainage procedure had been performed in sixteen of the postoperative subjects studied, selective vagotomy with a drainage procedure in seventeen, and partial gastrectomy in fifteen.

2. Patients in whom the glucose produced dumping symptoms had significantly greater enteroglucagon concentrations than those who were symptom-free, which confirms the results of a preliminary study. There was a highly significant correlation between the rate of rise of plasma enteroglucagon and the rate of fall of plasma volume.

3. There was no difference in the rate of rise or in peak plasma enteroglucagon concentration between the groups of patients who had different operative procedures. This suggests that enteroglucagon release is not under vagal influence.

4. There was no apparent relation between the plasma enteroglucagon concentration and the time-interval between the operation and the time of study, which implies that the exaggerated release of enteroglucagon after operation occurs in response to the altered gastric physiology and that there is minimal adaptive change.
The Contribution of Plasma Protease Inhibitors to Antiplasmin Activity in Man
Authors: Crawford G. P. M. , Ogston D. , Douglas A. S.
Published: August 2015

1. Human plasma contains a variety of proteins that are capable of inhibiting plasmin activity. Whole plasma possesses ‘rapid’ and ‘progressive’ plasmin-neutralizing activity: this study assesses the contribution of individual protease inhibitors to this plasmin-neutralizing property of plasma.

2. Rapid and progressive antiplasmin activities of human plasma correlate with α2-macroglobulin and α1-antitrypsin concentrations respectively.

3. Fluctuations in the amounts of the other measured inhibitors (antithrombin III, Cl inactivator and inter-α-trypsin inhibitor) did not influence the measured antiplasmin activity.
Comparison of Heart Sarcolemmal Enzyme Activities in Normal and Cardiomyopathic (UM-X7.1) Hamsters
Authors: Dhalla N. S. , Singh J. N. , Bajusz E. , Jasmin G.
Published: August 2015

1. The activities of some membrane-bound enzymes such as adenylate cyclase, Na++K+-stimulated adenosine triphosphatase (Na++K+-ATPase), Ca2+-stimulated ATPase and Mg2+-stimulated ATPase were examined in heart sarcolemmal fractions from control and cardiomyopathic hamsters at different stages of heart failure.

2. The basal adenylate cyclase activity in sarcolemma from cardiomyopathic animals with early, moderate and late stages of heart failure was not different from the control values whereas the sodium fluoride- and catecholamine-stimulated adenylate cyclase activities were depressed in cardiomyopathic sarcolemma at moderate and late stages.

3. The sarcolemmal Na++K+-ATPase activity was decreased and the non-specific phosphatase activity was increased at early, moderate and late stages of heart failure.

4. The sarcolemmal Ca2+-ATPase activity was decreased at moderate and late stages whereas the Mg2+-ATPase activity was decreased at the late stages of heart failure only.

5. A marked decrease was found in calcium binding by heart sarcolemma from cardiomyopathic hamsters at late stages of failure.

6. These results suggest that dramatic sarcolemmal changes are associated with heart failure, and support the view that membrane abnormalities play a crucial role in the development of myocardial dysfunction.
Haemodynamics and Body Fluid Volumes in Response to Fluid Loading in Conscious Dogs: Non-Excretory Renal Influences
Authors: Liard J.-F.
Published: August 2015

1. Twelve conscious, chronically instrumented dogs were subjected to rapid loading with sodium chloride solution (150 mmol/l; saline) before and 1 day after bilateral nephrectomy (six dogs) or uretero-caval anastomosis (six dogs). Measurements were performed up to 3 h after the fluid load and included cardiac output with an electromagnetic flowmeter, mean arterial pressure and right atrial pressure with chronically implanted catheters, interstitial fluid pressure with a plastic capsule, heart rate, extracellular fluid volume, erythrocyte volume, plasma volume, plasma protein concentration and other variables.

2. The increase in cardiac output in response to saline load was significantly prolonged in the anephric dogs compared with those with uretero-caval anastomosis; mean arterial pressure, right atrial pressure and heart-rate changes were similar in both groups.

3. Plasma volume appeared to increase more in the anephric dogs than in those with uretero-caval anastomosis during the first hour after the infusion, although conflicting results were obtained with different estimates of plasma volume changes. Interstitial fluid pressure increased significantly less in the anephric dogs in the early stages of the fluid load.

4. Effective vascular compliance (the ratio of the change in blood volume to the change in right atrial pressure) appeared increased in the anephric dogs. On the other hand, the change in cardiac output for a given change in right atrial pressure was found to increase after bilateral nephrectomy.

5. It is suggested that the prolonged increase in cardiac output observed in anephric dogs was not the consequence of preferential plasma volume expansion nor of decreased venous compliance, but may reflect an alteration in the cardiac function curve.
The Esterification of Exogenous Fatty Acids by Adipose Tissue of Hypertriglyceridaemic Subjects with or without Diabetes Mellitus
Authors: Clifton-Bligh P. , Galton D. J.
Published: August 2015

1. The esterification of exogenous palmitate to diglyceride and triglyceride in adipocytes was studied in obese and diabetic patients with and without hypertriglyceridaemia. The rate of esterification correlated significantly with the triglyceride content of adipocytes.

2. In diabetic patients with hypertriglyceridaemia, the rate of esterification to triglyceride was significantly greater than in diabetic patients with normotriglyceridaemia. This difference could not be attributed to differences in glucose tolerance or to the degree of obesity.

3. Fasting plasma insulin levels were greater in the hypertriglyceridaemic group than in the normotriglyceridaemic group. The difference in esterification rates could have been due to differences in adipocyte size.

4. The esterification of fatty acid in adipose tissue of diabetic patients was lower than in non-diabetic subjects and this difference could not be accounted for by differences in adipocyte size or differences in the intracellular pools of fatty acid in adipose tissue.

5. The role of esterification of exogenous fatty acids in adipose tissue as a possible determinant of the uptake of glyceride fatty acids from plasma is discussed.
Generation of Ammonia from Non-Urea Sources in a Faecal Incubation System
Authors: Vince A. , Down P. F. , Murison J. , Twigg F. J. , Wrong O. M.
Published: August 2015

1. A 25% faecal suspension in sodium chloride solution, incubated anaerobically at 37°C for 48 h, showed excellent survival of all the main groups of faecal bacteria.

2. All faecal incubation systems studied generated large amounts of ammonia, particularly those in which bacterial counts fell during incubation. As normal faeces contain negligible amounts of urea this ammonia must have been generated from sources other than urea.

3. Ammonia was also generated by faeces delivered by sodium chloride enema, and by ileostomy fluid, indicating that the phenomenon is not confined to distal colonic contents.

4. Ammonia generation by incubated faeces was inhibited by prior autoclaving of the sample, but not by sterilization with gamma-irradiation.

5. Generation of ammonia by incubated stool was accompanied by release of large amounts of organic anion and a fall in pH.

6. These observations are interpreted as evidence that ammonia generated within the colon in situ is not derived exclusively from urea, but also from bacterial deamination of amino acids, peptides and proteins. Simultaneously bacterial activity generates large amounts of organic acid. The presence of living bacteria is not essential for ammonia generation, provided that bacterial enzymes are present.

7. Bacterial generation of organic solute in faeces which have left the body is sufficiently rapid to cast serious doubts on the validity of faecal centrifugation, or other time-consuming techniques involving lengthy handling of faeces, as methods of obtaining extracellular faecal fluid for measurements of organic constituents or ammonia.
Does the Renin—Angiotensin System Contribute to the Vascular Lesions in Renal Hypertensive Rats?
Authors: Dietz R. , Haebara H. , Lüth B. , Mast G. , Nemes Z. , Schömig A. , Szokol M.
Published: August 2015

1. Renal hypertensive rats with a normal or suppressed activity of the renin—angiotensin system develop vascular lesions which are similar to those observed in spontaneously hypertensive rats on high sodium diet.

2. Exposure of a vascular bed to high blood pressure results in a rapid damage of the vascular wall, irrespective of the state of the renin—angiotensin system.
Urinary Excretion of Peptides and of Hydroxyproline in Wilson's Disease
Authors: Asatoor A. M. , Milne M. D. , Walshe J. M.
Published: August 2015

1. A study has been made of peptide excretion in twenty cases of Wilson's disease, ligand-exchange column chromatography being used to separate peptides from free amino acids. Previous reports of excess of peptide output in the disease were confirmed and the excess was shown to be highly significant statistically.

2. A considerable fraction of the excess of peptide output was shown to consist of hydroxyproline-containing peptides derived from collagen degradation.

3. The method of rank correlation showed that the difference both in free amino acid and peptide-bound amino acid output in cases of Wilson's disease and in control subjects was mainly quantitative; the pattern of amino acid excretion was qualitatively similar in both groups.

4. Evidence is presented that the increased copper output in the urine in the disease is not secondary to peptiduria.
A Study in Vivo of Peritubular Oncotic Pressure and Proximal Tubular Reabsorption in the Rat
Authors: Conger J. D. , Bartoli E. , Earley L. E.
Published: August 2015

1. Peritubular capillary microperfusion was used to examine the effects of protein-free and hyperoncotic homologous plasma on fluid reabsorption by proximal convoluted tubules in the hydropenic rat. 3H-labelled p-aminohippurate was added to perfusates for the purpose of estimating the extent to which tubules under study were bathed by the perfusates. [14C]Mannitol was added to perfusates in order to detect contamination of collected tubular fluid by perfusates.

2. Hydrostatic pressures were monitored in the peritubular microvasculature and adjacent proximal tubules during perfusion. Evidence for secretion of p-aminohippurate from perfusate into tubules under study was determined by collecting tubular fluid from both early and late puncture sites. Fractional and absolute reabsorption were not affected by either the protein-free or the hyperoncotic plasma.

3. When acetazolamide was added to the perfusate both fractional and absolute reabsorptive rates decreased by an average of 36%, indicating that the techniques were capable of detecting a decrease in proximal tubular reabsorption.

4. It is concluded that under the conditions of this study changes in peritubular capillary protein concentrations have no detectable effect on the rate of proximal convoluted tubule fluid reabsorption.
Intravenous Fat-Tolerance Test in Ischaemic Heart Disease and Peripheral Vascular Disease
Authors: Lewis B. , Onitiri A. C. , Wootton I. D. P. , Chait A. , Sigurdsson G. , Oakley C. M.
Published: August 2015

1. The intravenous fat-tolerance test and serum lipid and lipoprotein measurements were carried out in ninety-three normal subjects, fifty-one patients with ischaemic heart disease and thirty patients with peripheral vascular disease.

2. The fractional turnover rate of exogenous triglyceride was significantly slower in patients with ischaemic heart disease and in patients with peripheral vascular disease than in normal men. The rate was also slower in normal men than normal women.

3. Serum triglyceride and cholesterol concentrations were higher in both vascular disease groups than in control subjects.

4. The proportion of both groups of patients who had a subnormal fractional turnover rate of exogenous triglyceride was 35%, and 32% of patients had hypertriglyceridaemia in the fasting state; 27% of patients were hypercholesterolaemic.

5. Although the intravenous fat-tolerance test did not provide significantly better discrimination between cardiovascular patients and control subjects than did measurement of serum triglyceride, the results suggest that hypertriglyceridaemia in such patients may be separable into a group in which impaired triglyceride clearance may be partly responsible, and a group in which overproduction of serum triglyceride may be the major mechanism of the hyperlipidaemia.
The Influence of Orthophosphate on the Renal Handling of Inorganic Pyrophosphate in Man and Dog
Authors: Russell R. G. G. , Bisaz Sylvia , Fleisch H.
Published: August 2015

1. The urinary excretion of inorganic pyrophosphate (PP1), a known inhibitor of the growth and aggregation of crystals of calcium phosphate and calcium oxalate, increases after ingestion of orthophosphate (P1). This effect may contribute to the apparent ability of oral phosphate to reduce the formation of urinary stones in man. This paper is a study of the mechanism by which P1 increases PP1 excretion, investigated by renal clearance techniques in man and renal arterial infusion in dogs. PP1 in plasma was measured by an isotope-dilution method after ion-exchange chromatography.

2. The mean renal clearance of endogenous PP1 in ten men was 7·9 ± 1·7 (se) ml/min, and the mean ratio of PP1 clearance to creatinine clearance was 008 ±002 (se). The oral ingestion of P1 increased the urinary excretion and renal clearance of PP1 about threefold, without significantly changing its concentration in plasma.

3. In dogs, the infusion of P1 into one renal artery caused a greater increase in urinary PP1 from the infused than from the non-infused kidney, an effect that could be accentuated by simultaneous intravenous infusion of PP1. In dogs, only 1–3% of an injected or infused dose of PP1 appeared intact in the urine, regardless of whether it was infused into the systemic or renal circulation.

4. These results suggest that P1 has a direct effect on the kidney to increase the excretion of PP1. It is possible that P1 either interferes with tubular reabsorption of PP1, perhaps by competing for a common tubular transport mechanism, or that P1 diminishes the intrarenal hydrolysis of PP1.