bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Tryptophan Load and Vitamin B6 Supplementation on Urinary Excretion of Tryptophan Metabolites in Human Male Subjects
Authors: Wolf H. , Brown R. R.
Published: August 2015

1. Urinary excretion of tryptophan metabolites of the kynurenine pathway before and after a loading dose of 2 g of l-tryptophan (both before and during supplementation with vitamin B6) was studied in normal young male subjects and in elderly male subjects with prostatic diseases.

2. The increase in urinary excretion of tryptophan metabolites in the normal male subjects after a loading dose of 2 g of l-tryptophan was unchanged after vitamin B6 supplementation, indicating that this dose does not exceed the normal capacity of the kynurenine pathway.

3. It is therefore concluded that a loading dose of 2 g of l-tryptophan is preferable when studying the capacity of the kynurenine pathway.

4. In about three-quarters of the elderly male subjects with prostatic diseases, the capacity of the kynurenine pathway was normal.

5. In about one-quarter of the subjects with prostatic diseases after a loading dose of 2 g of l-tryptophan there was abnormally high urinary excretion of one or several tryptophan metabolites, which could be normalized by vitamin B6, indicating that the capacity of the kynurenine pathway had been exceeded in these subjects.

6. Urinary excretion of individual tryptophan metabolites after a loading dose of 2 g of l-tryptophan was constant in the same subject when studied under unchanged conditions, whether there was a normal or a decreased capacity of the kynurenine pathway.

7. It is concluded that a single determination of urinary excretion of tryptophan metabolites after a loading dose of 2 g of l-tryptophan is sufficient to determine the capacity of the kynurenine pathway.
The Ability of Man to Detect Added Resistive Loads to Breathing
Authors: Noble M. I. M. , Frankel H. L. , Else Wendy , Guz A.
Published: August 2015

1. Resistive loads were added to the airways of patients with tracheostomies; the patients were blindfolded and the loads introduced without their knowledge.

2. The ability to detect the loads was the same in a patient with C3 transection (chest wall and diaphragm disconnected from the brain) as in a control group of patients with no neurological lesion.

3. It is concluded that receptors in the chest wall and diaphragm are not involved in the genesis of the sensation by which added resistive loads are detected.
Rates of Absorption by rat Intestine of Pancreatic Hydrolysates of Proteins and Their Corresponding Amino Acid Mixtures
Authors: Crampton R. F. , Gangolli S. D. , Simson Pamela , Matthews D. M.
Published: August 2015

1. Though the occurrence of intestinal mucosal uptake of intact peptides, with cellular hydrolysis to amino acids, has been established, the importance of this mode of absorption in protein absorption is not known. This paper describes a comparison of the rates of intestinal absorption of pancreatic hydrolysates of four proteins with those of the corresponding acid hydrolysates or amino acid mixtures.

2. The results show that the absorption of pancreatic hydrolysates, consisting largely of small peptides of two to six amino acid residues, is substantially more rapid than that of the corresponding mixtures of free amino acids. This shows that the small intestine has a high capacity for absorption from mixtures of small peptides such as might be produced during protein digestion, and supports the hypothesis that mucosal uptake of intact oligopeptides is an important mode of protein absorption.
The Reflex Stimulation of Catecholamine Secretion during the Acute Stage of Myocardial Infarction in the Dog
Authors: Staszewska-Barczak Janina
Published: August 2015

1. The mechanism of catecholamine secretion after coronary occlusion was investigated in open-chest, anaesthetized dogs; the blood-bathed organ technique was used for continuous measurement of the changes in concentration of circulating catecholamines.

2. In dogs with increased output of adrenaline during the first hour after acute coronary occlusion, topical application of lignocaine to the infarcted area of the heart, spinal block at C1, bilateral section of thoracic splanchnic nerves, or ganglionic blockade virtually abolished adrenaline secretion.

3. Adrenaline secretion was abolished by bilateral vagotomy in 50% of the dogs, decreased in 28% and unchanged in the remaining 22%. Bretylium or guanethidine had no effect on adrenaline secretion in the early stages of myocardial infarction.

4. Seventeen of nineteen reserpinized dogs failed to secrete catecholamines during the first hour of coronary occlusion, even though the adrenal medulla responded to bradykinin, acetylcholine or nicotine. Noradrenaline infused either into the unoccluded carotid artery or intravenously restored adrenal medullary secretion.

5. When a sustained noradrenaline release occurred after coronary ligation, it was abolished by topical application of lignocaine to the ischaemic area of the heart or by ganglionic blockade. Neither bilateral vagotomy nor section of both thoracic splanchnic nerves suppressed noradrenaline liberation.

6. It is concluded that the adrenal medullary secretion of adrenaline which occurs in the early stages of myocardial infarction in the dog is induced reflexly from stimulation of cardiac receptors at the site and the boundary of the infarct. The reflex involves vagal as well as extra-vagal pathways and supraspinal structures. Enhanced liberation of noradrenaline in the early stage of infarction may reflect release from postganglionic sympathetic nerve endings in the heart.
The Role of Vasopressin and Urea in the Renal Concentrating Defect of Patients with Cirrhosis of the Liver
Authors: Vaamonde C. A. , Vaamonde Liliana S. , Presser J. I. , Morosi H. J. , Klingler E. L. , Papper S.
Published: August 2015

1. The maximal urine osmolality in response to vasopressin during water diuresis and during hydropenia was studied in twenty patients with cirrhosis and sixteen noncirrhotic subjects under controlled dietary conditions.

2. The cirrhotic patients exhibited a significantly lower maximal urine osmolality under both experimental conditions.

3. During water diuresis decompensated and compensated cirrhotics had comparable maximal urine osmolalities after vasopressin. A decreased response of the renal tubules to vasopressin does not appear to have a significant role in the concentrating defect.

4. The cirrhotic patients had a significantly lower excretion rate of urea at high (water diuresis) and low (vasopressin antidiuresis or hydropenia) urine flow rates. The lower urine urea concentration accounted for most of the decrease observed in maximal urinary concentration. After vasopressin administration the absolute tubular reabsorption of urea was also significantly lower in cirrhotic patients. The results suggest that a decrease in the medullary urea content decreases medullary osmolality resulting in the defect in urine concentration noted in these cirrhotic patients at low urine flow rates.

5. Protein depletion or decreased urea synthesis may in part be responsible for the decreased availability of urea for the concentrating process in cirrhosis.

6. Lack of correlation between concentrating and diluting capacity in these patients suggested that decreased delivery of sodium to the distal site might not be the limiting factor common to both renal functional abnormalities observed in cirrhosis of the liver.
Intrarenal Distribution of Blood Flow during Saline Loading in the Dog
Authors: Bovee K. C. , Webster G. D.
Published: August 2015

1. The effect of infusion of iso-osmotic saline on renal haemodynamics was studied to determine if the natriuresis that follows is associated with parallel and constant changes in renal cortical or outer medullary blood flow.

2. Blood flow was determined by external monitoring of the washout of 133Xe and the clearance of p-aminohippurate at two rates of saline loading in anaesthetized dogs.

3. After moderate saline loads (40 ml/kg body weight), increase in blood flow was limited to the renal cortex. After large saline loads (80 ml/kg body weight), a significant increase in outer medullary flow occurred in addition to increased cortical flow.

4. Changes in outer medullary blood flow as measured by the washout of 133Xe agreed with those predicted from the extraction of p-aminohippurate.

5. The extent of natriuresis did not consistently correlate with changes in either cortical or outer medullary blood flow. Whereas increases in renal blood flow were associated with a brisk natriuresis, it appears there is no simple relationship between increased cortical or outer medullary flow and sodium excretion.
The Oxygen-Transporting System in Relation to Age
Authors: Davies C. T. M.
Published: August 2015

1. An extensive study of the functional and dimensional components of the oxygen-transporting system in relation to age and the indirect estimation of maximum aerobic power (V̇o2max.) has been conducted on eighty healthy male subjects aged 20–50 years. Measurements were made of ventilation, cardiac frequency and blood lactic acid expressed in terms of oxygen intake of 1·51/min (V̇e, 1·5; fh, 1·5 and LA, 1·5 respectively) maximum blood lactic acid, ventilation and oxygen intake, thigh (TM) and calf (CM) and total body muscle estimated from soft tissue radiographs, whole body potassium (40K), blood volume (BV), heart volume (HV), and tests of lung function.

2. In the younger subjects it was shown that the functional and dimensional capacities of the O2-transporting system were closely integrated and the performance of organs in relation to size was essentially similar. In older subjects there was a gradual decline in the overall capacity to transport oxygen which was closely associated with a decrease in the functional rather than the dimensional aspects of the cardiovascular system. In terms of a given body weight the dimensional capacities of the older subjects, BV, THb (total body haemoglobin), 40K, TM CM, were shown to be independent of age.

3. The best single guide to V̇o2max. was given by BV in subjects under 35 years of age and by HV in older subjects. By using a multiple regression on either V̇e, 1·5, fh, 1·5 and leg muscle or FVC, HV, TM and age, V̇o2max. could be estimated with coefficient of variation of ∼9%. This is ∼2% improvement on conventional methods of determining V̇o2max. from measurements of fh and V̇o2 taken at four levels of work and in addition when using the latter equation there is no need for the subject to exercise. The use of these equations and their clinical application to the testing of V̇o2max. in large community studies of physical working capacity are discussed.
The Effects of Sodium Loading and Deprivation on Plasma Renin and Plasma and Urinary Aldosterone in Hypertension
Authors: Coghlan J. P. , Doyle A. E. , Jerums G. , Scoggins B. A.
Published: August 2015

1. Measurements of urinary aldosterone excretion and of peripheral venous plasma concentrations of aldosterone, Cortisol and corticosterone have been made in hypertensive and normotensive patients after a sodium load and after dietary sodium restriction and ambulation.

2. Plasma concentrations of aldosterone, Cortisol and corticosterone did not differ significantly between the two groups of patients, but the rise in urinary aldosterone excretion was significantly greater in normotensive than in hypertensive patients after sodium restriction.

3. Division of the hypertensive patients into two groups according to the response in plasma renin on sodium restriction did not disclose any significant differences between responders and non-responders in respect of aldosterone or Cortisol, but the plasma corticosterone rose more in normotensive patients after sodium depletion than in the unresponsive hypertensive patients.

4. It is concluded that both the rise in plasma renin and in aldosterone excretion rate are blunted in hypertensive patients after sodium restriction. It is suggested that this may be due to a rise in total body sodium in hypertensive patients.

5. Differences in aldosterone excretion rate are not reflected in the values of peripheral venous concentrations, presumably because of the short-term rise in plasma aldosterone which results from ambulation.
Role of the Kidney in ‘Salt and Water Dependent Hypertension’ of End-Stage Renal Disease
Authors: Bianchi G. , Ponticelli C. , Bardi U. , Redaelli B. , Campolo L. , De Ponti C. , Graziani G.
Published: August 2015

1. Blood pressure, plasma renin concentration, exchangeable body sodium, plasma volume and extracellular fluid volume were measured in five patients on maintenance haemodialysis for end-stage renal disease in whom hypertension was relatively easy to control by the combination of dialysis and restriction of salt intake. Measurements were made on three occasions: on a free salt intake the day before dialysis; on a low salt intake the day after dialysis; on a free salt intake the day before dialysis after nephrectomy.

2. The fall of blood pressure after haemodialysis and salt intake restriction was accompanied by a decrease of exchangeable body sodium and body fluids while plasma renin concentration increased. The fall of blood pressure after bilateral nephrectomy was accompanied by a fourfold decrease of plasma renin without any change of the other variables.

3. The hypertension of these patients might thus be considered ‘salt and water dependent’ or ‘renin dependent’ according to the means used to decrease blood pressure.
The Effects of Synthetic Human and Salmon Calcitonins on Electrolyte Excretion in the Rat
Authors: Williams C. C. , Matthews E. W. , Moseley Jane M. , MacIntyre I.
Published: August 2015

1. The effects on renal electrolyte excretion of human and salmon synthetic calcitonins were studied in the rat.

2. As little as 50 ng of salmon calcitonin produced an increase in sodium excretion, but human calcitonin in doses up to 15 μg had only a slight effect.

3. Small doses of both hormones decreased urinary calcium and magnesium. Larger doses of salmon calcitonin produced less depression of calcium and magnesium excretion even in the presence of a greater fall in plasma calcium.

4. The mechanisms responsible for these effects and the possible therapeutic implications are discussed.
Role of Pulmonary Vagal Afferent Nerve Fibres in the Development of Rapid Shallow Breathing in Lung Inflammation
Authors: Trenchard Diana , Gardner D. , Guz A.
Published: August 2015

1. The administration of the polysaccharide carageenin through a catheter into the lungs of cats and rabbits has produced an inflammatory lesion confined to one lobe of a lung. The lesion consisted of an alveolar and interstitial infiltration with polymorphonuclear leucocytes and, subsequently, macrophages. There was no apparent damage to alveolar walls and no pleurisy. The rest of the lung remained normal.

2. In both conscious cats and anaesthetized rabbits there was an increased frequency of breathing dependent on an intact vagus nerve on the same side as the lesion. It was independent of changes in body temperature and was not due to hypoxaemia.

3. By using a direct current to the right cervical vagus nerve in the rabbits (with the left vagus nerve sectioned), it has been possible to block conduction in myelinated fibres; the non-myelinated fibres conduct normally. Studies with this differentially blocked nerve have shown that the increased frequency of breathing is dependent on activity in the non-myelinated vagal afferent fibres.
Oral Contraceptives and Folate Metabolism
Authors: Stephens M. E. M. , Craft I. , Peters T. J. , Hoffbrand A. V.
Published: August 2015

1. There are conflicting reports regarding the effect of oral contraceptives on serum and erythrocyte folate concentrations and on folate absorption. A detailed study of this problem was therefore undertaken.

2. It was first ascertained that there was no significant variation in serum folate concentrations at different stages in the normal menstrual cycle.

3. No significant difference was found in fasting serum folate concentrations between control subjects and those taking oral contraceptives.

4. Synthetic sex hormones did not inhibit jejunal pteroylpolyglutamate hydrolase in vitro.

5. Tests of absorption of pteroylglutamic acid (folic acid) and pteroylpolyglutamates in controls and women taking oral contraceptives showed no difference between the two groups, provided the subjects were presaturated with pteroylglutamic acid. Without presaturation, the rise in serum folate after oral pteroylpolyglutamates was significantly decreased in the women taking oral contraceptives, suggesting that the latter may alter folate clearance from the blood.
Experimental Vitamin B6 Deficiency and the Effect of Oestrogen-Containing Oral Contraceptives on Tryptophan Metabolism and Vitamin B6 Requirements
Authors: Rose D. P. , Strong R. , Adams P. W. , Harding P. E.
Published: August 2015

1. A vitamin B6-deficient diet was fed to an adult male subject to confirm previously described changes in tryptophan metabolism and urinary 4-pyridoxic acid excretion, and erythrocyte alanine and aspartate aminotransferase activities.

2. The results were compared with those obtained in women taking oestrogen-containing oral contraceptives.

3. The development of dietary vitamin B6 deficiency was indicated by decreased 4-pyridoxic acid excretion, increased urinary concentrations of xanthurenic acid, kynurenine and 3-hydroxykynurenine, an elevated 3-hydroxykynurenine/3-hydroxyanthranilic acid ratio and impaired erythrocyte aminotransferase activities.

4. Tryptophan metabolites and 4-pyridoxic acid excretion were determined in thirty-one women when they had been taking an oral contraceptive for 6–36 months. Of these, twenty-six had abnormal tryptophan metabolism, but the 4-pyridoxic acid was decreased in only seven. In six of these seven a raised 3-hydroxykynurenine/3-hydroxyanthranilic acid ratio supported a diagnosis of subclinical vitamin B6 deficiency; erythrocyte alanine aminotransferase activity was determined in five of the six, and was decreased in three.

5. Erythrocyte aminotransferases were determined in sixteen women when they had been taking an oral contraceptive for 3–6 months, and in thirty-four women after 6–36 months treatment. Neither group showed any change in alanine aminotransferase activity, but the aspartate aminotransferase was elevated in the group treated for 6 months or longer.
Peripheral Airways Resistance, Static Recoil and the Forced Expiratory Volume
Authors: Cayton Ruth M. , Howard P.
Published: August 2015

1. The forced expiratory volume (FEV0·75) was measured at increasing mouth pressures in twenty-seven patients with obstructive airways disease. Attempts were made to divide the patients on clinical grounds into emphysematous, bronchitic or asthmatic categories; there was no evidence from the (FEV/mouth pressure) plots that their airways functioned differently during forced expiration.

2. Static elastic recoil was measured in twelve patients. There was no evidence that this factor alone caused the loss of FEV in any patient.

3. It is suggested that the use of the FEV as a test of respiratory function during the natural history of obstructive airways disease should be considered in three stages. There is an initial phase when peripheral airways disease develops with little or no alteration of the FEV. In the second phase the FEV decreases from normal values to below 1·0 litre, and at this stage is considered a sensitive indicator of peripheral airways resistance. In stage 3 the FEV is low and further changes can only be small. But airways resistance continues to increase and could be a more sensitive measurement of further airways disease.
Renal Calculi and Self-Medication with Multivitamin Preparations Containing Vitamin D
Authors: Taylor W. H.
Published: August 2015

1. Of 104 patients with renal calculi, 42% gave a history of previous self-medication with multivitamin preparations containing vitamin D, compared with 37% of a control group of fifty-one patients without renal calculi. This difference is not significant.

2. The mean supplemental daily intake of vitamin D and the annual intake were significantly higher in the patients with renal calculi than in the control group.

3. The highest mean supplemental intake of vitamin D occurred among those patients in whom no metabolic or other cause for renal stone formation could be found.

4. The first calculi presented within 2 years of the period of self-medication in twenty-four of thirty patients who had not previously suffered from renal stones.

5. The results suggest that self-administration of vitamin D should be included among the aetiological factors promoting the formation of renal calculi.
Effect of Intraluminal Concentrations on the Impairment of Glycine Absorption by Glucose in the Human Jejunum
Authors: Cook G. C.
Published: August 2015

1. To investigate the effect of different intraluminal concentrations on the mutual inhibitive effect of glycine and glucose on their jejunal absorption rates, eighteen convalescent Zambian African patients who had no clinical evidence of intestinal disease or of malnutrition were given constant intrajejunal infusions with those solutes either together or alone. A double-lumen tube perfusion system was used, and three solutions containing (A) glycine, (B) glycine and glucose, and (C) glucose, all of which were rendered iso-osmotic with sodium chloride, were perfused in random order at 12·0 ml/min. The concentration of glycine in the perfusing fluid was either 10 or 20 mm, and that of glucose either 100, 200 or 280 mm. By reference to polyethylene glycol 4000, the absorption rates of the solutes and water were calculated for a 30 cm jejunal segment.

2. At a glucose concentration of 200 or 280 mm, but not 100 mm, the mean rate of glycine absorption was decreased by approx. 30%. Glucose absorption rates were not significantly altered by glycine.

3. These observations, taken in conjunction with those from a previous investigation, are consistent with the view that there are two mechanisms for the jejunal absorption of glycine in man, one of which is inhibited by glucose at high intraluminal concentration.
Inhibition of Sodium and Potassium Transport in Separated Renal Tubule Fragments Incubated in Extracts of Urine Obtained from Salt-Loaded Individuals
Authors: Clarkson E. M. , De Wardener H. E.
Published: August 2015

1. Extracts of urine were prepared from salt-depleted and salt-loaded subjects by gel filtration of freeze-dried urine on Sephadex G-50. The extracts were dissolved and adjusted to physiological pH and electrolyte concentration.

2. Separated renal tubule fragments were prepared from rabbit kidney cortex and their intracellular sodium and potassium measured after incubation in the dissolved adjusted extracts. Those concerned with the measurement of intracellular sodium and potassium did not know the identity of the samples.

3. Extracts of urine from salt-loaded subjects inhibited the sodium and potassium transport of the tubules whereas extracts of urine from salt-depleted subjects had no effect.

4. Of ten known hormones that were tested, none had any inhibitory effect on the sodium transport of the tubule fragments.

5. It is concluded that the oral intake of large amounts of salt in normal subjects causes the appearance of an unknown substance in the urine which inhibits sodium transport in separated renal tubule fragments.
Mechanisms of Excretion of Some Low-Molecular-Weight Bases in the Rat
Authors: Bourke E. , Asatoor A. M. , Milne M. D.
Published: August 2015

1. The excretion of structural analogues of ammonia in acidic and alkaline urine was investigated. The lipid-soluble compounds n-propylamine, n-butylamine and n-amylamine and the water-soluble compounds hydrazine and methylhydrazine resemble ammonia in being more rapidly excreted in acidic urine. By contrast, the excretion of the water-soluble amines methylamine and ethylamine is unaffected by changes in urinary pH.

2. Arguments are advanced, based on the results, that pH-dependent excretion of ammonia is due to diffusion of the water-soluble un-ionized fraction through the aqueous phase of the cell membrane, and the same applies to the hydrazines. However that of n-propylamine and the higher-molecular-weight alkylamines is due to diffusion through the lipid phase of the cell membrane. The data suggest that this latter form of diffusion is the more rapid one.

3. After injection of glutamyl-γ-methylamide and the corresponding ethylamide, both methylamine and ethylamine excretions are significantly higher in acidosis, rising further in chronic acidosis. This indicates that the glutaminase II pathway of ammonia genesis increases in activity in the acidotic rat in vivo.
Excretion of Propionylglycine in Propionic Acidaemia
Authors: Rasmussen K. , Ando T. , Nyhan W. L. , Hull D. , Cottom D. , Donnell G. , Wadlington W. , Kilroy A. W.
Published: August 2015

1. The urinary excretion of acylglycines has been studied in four patients with propionic acidaemia.

2. Propionylglycine was found in each of the patients.

3. This compound has not previously been detected in human body fluids. Propionylglycine was not present in the urine of control subjects or patients with non-ketotic hyperglycinaemia.

4. The excretion of propionylglycine was greatest in patients receiving the least dietary control.
Renin and Control of Arterial Blood Pressure during Terminal Renal Failure Treated by Haemodialysis and by Transplantation
Authors: Verniory A. , Potvliege P. , Van Geertruyden J. J. , Vereerstraeten P. , Kinnaert P. , Staroukine M. , Toussaint C.
Published: August 2015

1. Plasma renin concentrations were determined in 1068 samples obtained in 113 patients in the end stage of chronic renal failure treated by repeated haemodialyses or by renal transplantation.

2. Patients with malignant nephroangiosclerosis have a very high concentration of plasma renin; this differentiates them from other disease groups, where renin concentration is sometimes normal and sometimes elevated; there is no significant difference between the glomerulonephritis and pyelonephritis groups.

3. There is a weak but significant correlation between plasma renin concentration and arterial blood pressure. In the terminal stage of chronic renal insufficiency, blood pressure appears to be controlled by other quantitatively more important factors. However, the hypertension of some cases, characterized by high concentrations of plasma renin, can be controlled only by bilateral nephrectomy.

4. There is an inverse and highly significant correlation between plasma renin and sodium concentrations. This is also the case in transplanted patients where an inverse correlation also exists between plasma renin concentration and daily urinary output of sodium.

5. The juxtaglomerular granulation index correlates positively with the plasma renin concentration.

6. In terminal renal failure the kidney retains its capacity to secrete renin as a response to acute haemorrhage or other stimuli.

7. Renin is present in the blood of anephric patients and its concentration is not correlated either with the patient's sex or with the time elapsed after binephrectomy.

8. During rejection episodes in transplanted patients a rise of plasma renin concentration is frequently but not invariably observed. Elevation of plasma renin concentration is evident in very acute rejection crises.
Water and Sodium Excretion after Blood Volume Expansion under Conditions of Constant Arterial, Venous and Plasma Oncotic Pressures and Constant Haematocrit
Authors: Lichardus B. , Nizet A.
Published: August 2015

1. The diuretic and natriuretic responses occurring during expansion of blood volume by homologous blood transfusion were studied in homologous kidneys transplanted to the neck of hydropenic dogs that had previously been given deoxycorticosterone acetate and antidiuretic hormone. The experimental conditions ensured constant arterial perfusion pressure, venous pressure, osmotic pressure, haematocrit and plasma oncotic pressure.

2. Moderate but significant increases in urine output, renal sodium excretion, osmotic clearance and tubular sodium rejection fraction were observed; there were no significant changes in glomerular filtration rate, renal blood flow, postglomerular haematocrit and postglomerular plasma protein concentration 20 and 40 min after the end of blood infusion.

3. As the non-hormonal factors known to modulate sodium excretion underwent no significant change, the results are compatible with the proposition that a specific factor (‘natriuretic hormone’) plays a role in the mechanism of natriuresis after blood volume expansion.
Reversibility of Airways Obstruction in Chronic Bronchitis
Authors: Astin T. W.
Published: August 2015

1. Airways resistance and lung volume were measured in twenty-five patients with chronic bronchitis and fifteen patients without chest disease before and after the inhalation of isoprenaline. Similar measurements were made on fourteen of these patients with chronic bronchitis and twelve other patients without chest disease before and after the intravenous injection of atropine sulphate.

2. There were significant decreases in airways resistance after isoprenaline inhalation and intravenous atropine both in patients with bronchitis and normal subjects but the decreases were greater in the patients with chronic bronchitis.

3. The decrease in resistance was proportional to the degree of initial airways resistance.

4. The results are considered to indicate that bronchial muscle contraction increases the airways resistance of patients with chronic bronchitis and contributes to the airways obstruction; its contribution increases with increasing severity of the condition. A significant part of the increased airways resistance in these patients is potentially reversible and nervously mediated.
The Effect of Experimental Immune Complex Nephritis on Rat Serum Proteins
Authors: Horne C. H. W. , Toner P. G.
Published: August 2015

1. A radial immunodiffusion technique was used to determine the concentrations of five rat serum proteins, slow α1- and α2-globulin, transferrin, albumin and γ2-globulin before and after the induction of immune complex nephritis.

2. Four weeks after immunization with renal tubular antigen significant increases in transferrin, slow α2-globulin and γ2-globulin concentrations were observed but albumin showed a significant fall and slow α1-globulin did not change.

3. After the development of proteinuria 7 weeks after immunization significant falls in the concentrations of albumin transferrin and γ2-globulin were noted along with significant increases in the macroglobulins, slow α1- and α2-globulin, the changes being similar to those seen in the nephrotic syndrome in man.

4. At the end of the experiment the typical ultrastructural features of immune complex nephritis were observed.
Serum Bactericidal Activity in Patients with Upper and Lower Urinary Tract Infections
Authors: Gower P. E. , Taylor P. W. , Koutsaimanis K. G. , Roberts A. P.
Published: August 2015

1. Serum bactericidal activity against the homologous organism was determined in patients with urinary tract infections and has been related to the site of infection and to serum antibody titres.

2. A significantly higher number of patients with upper compared to lower urinary infections were found to have either a specific defect in bactericidal activity against the homologous organism or to be infected with organisms inherently resistant to normal serum bactericidal activity.

3. It is suggested that these factors may be important in determining the site of urinary tract infections.
The Influence of Two Diphosphonates on Calcium Metabolism in the Rat
Authors: Gasser A. B. , Morgan D. B. , Fleisch H. A. , Richelle L. J.
Published: August 2015

1. The effects of two diphosphonates, disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) and disodium dichloromethylene diphosphonate (Cl2MDP) on several variables of calcium metabolism have been measured in the intact rat using the model of Aubert & Milhaud (1960).

2. The animals were bred from weaning on a diet containing 1·3% calcium. At the age of 54 days they were switched to a diet with 0·5% calcium. Some of the animals were also given daily injections of one of the diphosphonates from the day the intake was decreased. The doses of the compounds were 0·01–10 mg of P kg body wt.−1 day−1.

3. Cl2MDP caused a decrease in the rates of bone formation (V0+) and bone resorption (V0–), and these effects were proportional to the logarithm of the dose of the compound. There was a small increase in the retention of calcium due to a decrease in the endogenous faecal calcium.

4. EHDP in doses of up to 1 mg of P kg−1 day−1 decreased bone resorption but had little effect on bone formation. The retention of calcium increased due to an increased absorption of dietary calcium and a decreased endogenous faecal calcium. EHDP at a dose of 10 mg of P kg−1 day−1 caused a further fall in V0_ but also a great decrease in V0+ which was larger than the fall in V0_. The net absorption of calcium was diminished, the urinary excretion of calcium was increased, the retention of calcium was greatly diminished and there was a greatly diminished ash content in the femur. Thus, for equal doses of up to 1 mg of P kg−1 day−1, Cl2MDP was more potent in decreasing bone turnover than EHDP, but the two compounds caused a similar increase in the retention of calcium. At high doses EHDP inhibited the mineralization of epiphyseal cartilage.

5. These results are discussed in relation to the possible clinical applications of the diphosphonates.
The Ventilatory Response to CO2 of Patients with Diffuse Pulmonary Infiltrations or Fibrosis
Authors: Patton J. M. S. , Freedman S.
Published: August 2015

1. We have used the rebreathing method to examine the respiratory response to CO2 in five normal subjects and twelve patients with diffuse pulmonary infiltration or fibrosis. The response to CO2 was measured in terms of both ventilation and mechanical work rate.

2. The response to CO2 was, on average, reduced in the patients compared with the normals but the patients had to perform more mechanical work to achieve a given level of ventilation.

3. Six patients had an abnormally low resting mixed venous Pco2 and four of these also had an abnormally low response to CO2.

4. The pattern of breathing was identical in patients and normals.

5. The results indicate that the reduced ventilatory response represents a true loss of CO2 sensitivity and is not simply due to mechanical limitation; but the paradox in some patients of resting hyperventilation and a low level of CO2 responsiveness is unexplained.
The Effect of Upper Abdominal Surgery on the Relationship of Airway Closing Point to End Tidal Position
Authors: Alexander J. I. , Horton P. W. , Millar W. T. , Parikh R. K. , Spence A. A.
Published: August 2015

1. The relationship between end tidal position (ETP) and the point of lung emptying at which there is significant airways closure (CP) has been investigated before and after upper abdominal surgery in thirty-one patients.

2. A significant negative correlation between the index (ETP-CP) and the alveolar-arterial Po2 difference (A-ado2) was found.

3. Nineteen of these patients had a vagotomy and drainage operation and, in this group, there was a greater fall in ETP than in CP in the first and second postoperative days.

4. It is suggested that airway closure is a contributory factor to the known hypoxaemia following abdominal surgery.
Observations on the Mechanism of Thiamine Hydrochloride Absorption in Man
Authors: Thomson A. D. , Leevy C. M.
Published: August 2015

1. The intestinal absorption of [35S]thiamine hydrochloride was investigated in healthy subjects, malnourished alcoholics and a patient with resection of the jejunum and ileum. Serum and urinary radioactivity was studied after administration of 10 μCi of [35S]thiamine hydrochloride in 1–50 mg of non-radioactive thiamine hydrochloride.

2. Results suggest that intestinal absorption of thiamine hydrochloride is rate-limited. Though the results provide only indirect information on intestinal transport rates, they are consistent with the Michaelis-Menten relationship used to describe enzyme-substrate reactions. Calculations by this model yielded a Vmax. of 8·3 ± 2·4 mg and a Km of 12·0 ± 2·4 mg for normal subjects with a significant decrease in Vmax. in malnourished alcoholics and a patient with resected small intestine.

3. Intestinal absorption and the calculated value of Vmax. for thiamine hydrochloride is increased in malnourished alcoholics after correction of malnutrition. These findings are consistent with the thesis that this vitamin is absorbed by a saturable mechanism and that the number of effective receptor sites may be reduced by malnutrition or intestinal resection.
The Effect of Vagotomy on the Lower Part of the Acid Dose-Response Curve to Pentagastrin in Man
Authors: Elder J. B. , Gillespie G. , Campbell E. H. G. , Gillespie I. E. , Crean G. P. , Kay A. W.
Published: August 2015

1. The acid secretory responses to insulin of forty-seven duodenal ulcer patients after truncal vagotomy and drainage were classified according to the criteria of Hollander (1946) into positive or negative.

2. The acid response to ranges of small doses of pentagastrin was studied in these two groups. In the group with a positive acid response after insulin the dose-response pattern to pentagastrin was very similar to that in preoperative patients.

3. In those who failed to satisfy criteria for a positive response after insulin the dose-response curve to pentagastrin appeared to shift to the right. It had a lower level and a smaller slope. Truncal vagotomy appeared to cause an eightfold increase in the threshold dose found in preoperative patients.

4. Supersensitivity of the stomach to small doses of pentagastrin after vagotomy was not apparent in the present study.
Arterial Angiotensin II and Venous Immunoreactive Material before and during Angiotensin Infusion in Man
Authors: Oelkers W. , Düsterdieck G. , Morton J. J.
Published: August 2015

1. Angiotensin II together with any immunoreactive fragments of angiotensin were measured in arterial and venous plasma before and during infusion of angiotensin II amide in five normotensive subjects, both in sodium-replete and sodium-depleted states. Because the antibody used in the radioimmunoassay cross-reacted with larger angiotensin breakdown products and because these fragments are present in higher concentrations in venous than arterial plasma, samples of both were assayed. Measurements on venous plasma are referred to as immunoreactive material (IM).

2. Arterial plasma angiotensin II concentration (PAC) and venous IM were compared in two additional subjects during infusion of angiotensin II amide and of synthetic human angiotensin II.

3. Arterial PAC and venous IM increased in linear relation to the dose of angiotensin infused, similar results being obtained with angiotensin II amide and synthetic human angiotensin II.

4. Before infusion, venous IM and arterial PAC were comparable (A:V ratio = 0·99 ± 0·16, n = 29). During infusion venous IM was consistently lower than arterial PAC; with angiotensin II amide the A:V ratio was 1·72 ± 0·49 (n = 35), and with synthetic human angiotensin it was 1·63 ± 0·2 (n = 6).

5. Results of an in vitro study suggest that the formation of new angiotensin in the vein is not sufficient to explain the lower A:V ratio of PAC before infusion.

6. It is proposed that arterial PAC rather than venous IM should be measured when the relationship between blood levels and biological effects of the peptide are the object of the study, particularly during angiotensin infusion or when rapid changes in circulating angiotensin occur.
Sodium Turnover in Irradiation Hypertension
Authors: Ermel A. E.
Published: August 2015

1. Changes in sodium turnover in experimental hypertension were studied by tracer kinetic methods after injection of the long-lived radioisotope 22Na.

2. In rats treated with renal irradiation, the pre-hypertensive latent period is characterized by a modified distribution of body sodium which can be interpreted as a transfer from peripheral stores to a more centrally located pool. Before the development of hypertension, the rapidly exchangeable sodium increased by 14%.

3. The rise in blood pressure to a hypertensive level is associated with a decrease in the fractional excretion rate of sodium. During the established phase of hypertension, serial determinations of exchangeable sodium indicate rapidly fluctuating shifts of body sodium, the significance of which remains unknown.
Characterization of the Natriuresis Caused in Normal Man by Immersion in Water
Authors: Epstein M. , Duncan D. C. , Fishman L. M.
Published: August 2015

1. The effects of 4–6 h of water immersion on the renal excretion of water and electrolytes were studied in thirteen normal male subjects in balance on a constant diet containing 150 mEq of Na and 100 mEq of K per day. Each subject was studied during a control period, consisting of quiet sitting, and during water immersion to the neck.

2. Immersion resulted in a natriuresis beginning within the first hour, with the rate of sodium excretion eventually exceeding that of the control period by 3–4-fold; potassium excretion also increased. Despite a progressively negative water balance during the immersion studies, urine flow was greater during the first 4 h and free water clearance was greater during the first 2 h of immersion than during the control study.

3. The demonstration of a highly significant increase in fractional excretion of sodium during immersion suggests that the natriuresis of water immersion is not attributable to changes in filtered sodium load.

4. The prompt onset of the natriuresis, the concomitant kaliuresis and the fact that aldosterone secretion under the conditions of study was probably already suppressed make it unlikely that the natriuresis of water immersion is mediated solely by decreases in aldosterone activity.

5. The data suggest that the natriuresis caused by water immersion is the result of decreased fractional reabsorption of sodium proximal to the renal diluting site. The mechanism whereby increased proximal tubular sodium rejection occurs in relation to immersion remains unclear.
Flow Dependence of the Intrapulmonary Distribution of Inspired Boluses of 133Xe in Smokers and Non-Smokers
Authors: Martin R. R. , Anthonisen N. R. , Zutter M.
Published: August 2015

1. Starting at 50% vital capacity, boluses of 133Xe were inhaled either at very low or maximal flow rates, the inspiration terminating at total lung capacity (TLC). Flow-dependent changes in bolus distribution were examined by measuring regional radioctivity and computing regional time-constants, and also by recording alveolar plateaux during the subsequent vital capacity expiration. Regional residual volumes, as a fraction of regional total lung capacities, were also calculated. Three groups of subjects were studied: young non-smokers, young cigarette smokers, and older non-smokers.

2. All three groups gave similar results in terms of regional time-constants though there was less variation in the results for young non-smokers.

3. Regional residual volumes also gave similar results in all groups although again there was less variation in young non-smokers. In young smokers, residual volumes in some regions depended on the flow rate used in their measurement, which indicated intraregional inhomogeneity of function.

4. In young non-smokers alveolar plateaux after slow and fast bolus inspirations differed little; this was not the case either in older subjects or in smokers. The increased flow-dependence of the alveolar plateau is analogous with the increased frequency-dependence of dynamic compliance and probably indicates obstruction of small peripheral airways.
The Effects of Low-Protein Diet and Uraemia upon Urea-Cycle Enzymes and Transaminases in Rats
Authors: Brown C. L. , Houghton B. J. , Souhami R. L. , Richards P.
Published: August 2015

1. Activities of arginine synthetase system enzymes, alanine aminotransferase (AlT) and branched-chain amino acid transaminase (BATase) were measured in control and uraemic rats after 2 weeks on a free protein intake and after 10 days on a low-protein diet.

2. Protein restriction alone reduced the activity of all three enzymes.

3. Uraemia alone increased the activity of arginine synthetase system enzymes and AlT. BATase was not altered.

4. After protein restriction the BATase activity in uraemic rats decreased to the same extent as in controls. The activity of arginine synthetase system enzymes and AlT were significantly higher than in protein-restricted controls and were the same as in control rats on a normal diet.

5. Practical consequences of the finding that uraemia prevented the decrease of AlT but not of BATase activity in response to a low-protein diet are discussed, with particular reference to reutilization of urea-nitrogen for the synthesis of non-essential and essential amino acids.
An Organ Culture Study of the Effect of Drugs on the Secretory Activity of the Human Bronchial Submucosal Gland
Authors: Sturgess Jennifer , Reid Lynne
Published: August 2015

1. The incorporation of tritiated glucose into bronchial gland cells enables their glycoprotein secretion to be followed by radioautography. The number of cells from which secretion is observed after 4 h of cell culture is the secretory index.

2. Large variations in secretory index were observed between the bronchi of different subjects, but the secretory index was proportional to gland size.

3. The secretory index was increased by parasympathomimetic drugs and diminished by parasympatholytic drugs, the magnitude of the effect being proportional to gland size in the former and inversely proportional in the latter case.

4. Sympathomimetic drugs, bradykinin and mucolytic drugs had no effect on the secretory index.

5. In cystic fibrosis, bronchitis and bronchiectasis gland size and not the disease process was the main determinant of the secretory index.
Capillary Diffusion Capacity for 131I in Muscles of Patients with Chronic Renal Insufficiency
Authors: Roztočil K. , Přerovský I. , Novák P.
Published: August 2015

1. Capillary diffusion capacity (CDC) for 131I in gastrocnemius muscle was investigated by the tissue clearance method of Lassen (1967) in thirty-three patients with various degrees of impairment of renal function.

2. The mean CDC in uraemic patients [16·9 mol/(mol/ml)/100 g/min] was significantly higher than in the control group [7·1 mol/(mol/ml)/100 g/min]. A comparison of patients with renal failure due to chronic glomerulonephritis with those in whom it was due to chronic pyelonephritis showed no significant difference.

3. The most likely interpretation of these observations is that capillary permeability is increased in uraemia.
Renal Excretion of Bicarbonate and Hydrogen Ions: Effects of Mannitol Diuresis in Normal Man
Authors: Poole-Wilson P. A. , Patrick J. , MacGregor G. A. , Jones N. F.
Published: August 2015

1. The pattern of urinary acid excretion during mannitol diuresis was studied in five normal adult subjects.

2. At peak diuresis (osmolal clearance 19·3–27·9 ml/min), the urinary pH approached 6·9 irrespective of the initial pH.

3. Total hydrogen ion excretion fell sharply during mannitol diuresis. Changes in the excretion of ammonium and titratable acid were small and variable, but in each subject bicarbonate excretion increased markedly.

4. Despite previous conflicting published results urinary acid excretion during mannitol diuresis in man resembles that in the dog and is dominated by a bicarbonate diuresis.