bluuebunny/crossref_metadata_2025 huggingface dataset:
Human Glomerular Membrane Porosity and Filtration Pressure: Dextran Clearance Data Analysed by Theoretical Models
Authors: Arturson G. , Groth T. , Grotte G.
Published: August 2015

1. The renal clearance of dextran of different molecular sizes has been measured in normal humans from 6 days to 61 years of age. Gel chromatography of dextran has been used for determination of molecular weight distribution.

2. Information about the functional ultrastructure of the glomerular membrane has been deduced from the experimental clearance data in the light of theoretical models. The glomerular membrane was here visualized as a gel filter, localized in the basement membrane. The physical analogue of this membrane was interpreted as a somewhat heteroporous structure of quite well defined pore sizes: one system of smaller pores in the range of 20–28 Å radius and an additional system of larger pores of radii up to 80 Å. These larger pores are quite few in number with an approximate ratio of one large pore per 10 000 small pores.

3. The values obtained for the transglomerular pressure difference were low, about 1 cm of water or less. This supports the concept that tubular reabsorption may be the rate limiting factor in the process of urine formation and may also control the glomerular filtration rate.

4. The changes of the dextran clearance with ageing found in this investigation may be explained by an increase of the pore radii of the glomerular membrane and a concomitant decrease of the transglomerular pressure difference.
Thermoregulation and Raynaud's Phenomenon
Authors: Downey J. A. , Leroy E. C. , Miller J. M. , Darling R. C.
Published: August 2015

1. Hand heat elimination was measured during central body heating or cooling to evaluate the sensitivity of thermoregulation in patients exhibiting Raynaud's Phenomenon.

2. Patients with Raynaud's Phenomenon responded to central heating and cooling very much as did normal subjects.

3. Patients with Raynaud's Phenomenon and associated connective tissue disease do not vasodilate in the hand in response to central heating as much as normals. These findings are compatible with the concept of a local structural defect in the blood vessels of the hand.

4. The nature of the abnormality causing Raynaud's Phenomenon is not apparent but it does not appear to be due to an increased sensitivity of the central thermoregulatory system.
Drug Interactions with Warfarin: Studies with Dichloralphenazone, Chloral Hydrate and Phenazone (Antipyrine)
Authors: Breckenridge A. , Orme M. L'E. , Thorgeirsson S. , Davies D. S. , Brooks R. V.
Published: August 2015

1. Administration of dichloralphenazone, a complex of chloral hydrate and phenazone (antipyrine) caused a fall in steady-state plasma warfarin concentration and loss of anticoagulant control in five subjects.

2. This effect of dichloralphenazone is due to stimulation of the drug-oxidizing enzymes of the liver endoplasmic reticulum by antipyrine, the non-hypnotic part of the complex. Administration of antipyrine caused a fall in steady-state plasma warfarin concentration in five subjects, a shortening of the plasma warfarin half-life, with increased urinary excretion of the metabolites of 14C-labelled warfarin in two subjects and increased urinary excretion of 6β-hydroxycortisol which is formed in the liver endoplasmic reticulum.

3. Administration of chloral hydrate, the hypnotic part of dichloralphenazone, caused no change in anticoagulant control but a fall in steady-state plasma warfarin concentration in five subjects. This is due to the accumulation of trichloroacetic acid which displaces warfarin from plasma protein binding sites.

4. Individual differences in the extent of enzyme induction have been shown to be related to the subjects' rates of drug oxidation.

5. In the rat administration of dichloralphenazone and antipyrine, but not chloral hydrate, caused shortening of pentobarbitone sleeping time and of the plasma [14C]pentobarbitone half-life, shortening of the zoxazolamine paralysis time and increase in the maximal velocity of N-demethylation of ethylmorphine.
Cardio-Respiratory Response to Exercise in Normal Children
Authors: Godfrey S. , Davies C. T. M. , Wozniak E. , Barnes Carolyn A.
Published: August 2015

1. The results of studies during simple progressive exercise to exhaustion and steady-state submaximal exercise in 117 boys and girls aged 6–16 years are presented.

2. In the simple progressive exercise test, the highest work load achieved and the submaximal heart rate were related to size and sex. The maximum heart rate and submaximal ventilation were largely independent of size and sex.

3. Steady-state exercise was performed at one-third and two-thirds of the maximum work load achieved in the simple progressive test. The Indirect (CO2) Fick method was used to measure cardiac output.

4. At any given level of steady-state work, tidal volume, dead space, heart rate and stroke volume were closely related to size, with girls having higher heart rates and smaller stroke volumes than boys. Minute ventilation and cardiac output were virtually independent of size and sex. The cardiac output in children was the same as that in the adult for any given oxygen consumption. Blood lactate was related to size at any given work load, but was independent of size at any given fraction of the maximum working capacity.
The Different Effects of Oral Sucrose and Glucose on Alimentary Lipaemia
Authors: Mann J. I. , Truswell A. S. , Pimstone B. L.
Published: August 2015

1. A formula breakfast containing protein, carbohydrate and fat was given on two occasions to nine middle-aged male convalescent patients and to ten young men. The meals differed only in the type of carbohydrate given; sucrose or an isocalorific amount of glucose.

2. After the formula meal containing sucrose; (a) the alimentary lipaemia was cleared more slowly; (b) insulin response was smaller, and (c) there was a lower blood sugar curve than after the glucose meal.

3. The degree of lipaemia showed a significant positive correlation with insulin response which was, as expected, lower after sucrose than glucose.

While attempting to confirm a report (Schilling, Hashim & Leonardy, 1964) that serum triglycerides are not significantly elevated after the ingestion of a small mixed meal, it was noticed that the triglyceride concentrations seemed to depend on the type of carbohydrate given (Mann & Truswell, 1971). Albrink, Fitzgerald & Mann (1958) and Sullivan (1960) have shown that the lipaemia which occurs after a fatty meal is diminished by the addition of glucose to the meal. Krut & Barsky (1964) found that postprandial lipaemia in patients with ischaemic heart disease is decreased by intravenous infusion of glucose and insulin.

These considerations led us to examine the effects of glucose and sucrose and subsequent insulin release on alimentary lipaemia.
Diuretics in Chronic Renal Disease: A Study of High Dosage Frusemide
Authors: Allison Marjorie E. M. , Kennedy A. C.
Published: August 2015

1. The efficacy and mode of action of frusemide (100–750 mg) have been studied acutely in thirty-four investigations on twenty-four water-loaded subjects with stable, non-oedematous chronic renal disease (GFR 2.3–26.0 ml/min) of varying aetiology (fourteen ‘tubular’, ten ‘glomerular’).

2. Water loading alone resulted in a slight increase in urine flow rate, a flow-dependent rise in electrolyte excretion and a small fall in urine osmolality.

3. Basal fractional excretion of fluid and electrolytes was closely related to GFR, increasing as this fell, so that at a GFR of 3.0 ml/min 80% of the fluid filtered, 50–60% of the filtered load of sodium and chloride and 400% of potassium was excreted.

4. After oral or intravenous frusemide, up to 93% of the filtered load of chloride, 87% of sodium and apparently all of the glomerular filtrate could be excreted; the magnitude of the response depended on dose, GFR and basal fractional sodium excretion, being greatest at higher GFR and lowest fractional excretion. Free water clearance increased.

5. No significant change in inulin clearance was found after frusemide and no difference in the response of ‘tubular’ as opposed to ‘glomerular’ subjects.

6. Long-term treatment of nineteen patients with ‘resistant’ oedema and chronic renal disease has shown high dosage frusemide (0.12–2.0 g/day) to be an effective diuretic, although significant side effects were found in five patients.
Studies on the Mechanism of Hypernatriuresis in Essential Hypertension in Relation to Measurements of Plasma Renin Concentration, Body Fluid Compartments and Renal Function
Authors: Schalekamp M. A. D. H. , Krauss X. H. , Schalekamp-Kuyken M. P. A. , Kolsters G. , Birkenhäger W. H.
Published: August 2015

1. In twenty-two patients representing different stages of benign essential hypertension, hyperosmotic saline was administered intravenously. Determinations of intra-arterial pressure, renal plasma flow, glomerular filtration rate and plasma renin concentration were carried out before and, in the majority, also during and after saline infusion. Changes in cardiac output were followed in ten patients. Plasma volume and extracellular volume were determined in the control period only, although haemodilution was assessed by haematocrit readings.

2. Excess of sodium excretion showed a wide range and was related to the patient's age, as well as to a set of parameters reflecting intrarenal pressure patterns; hypernatriuresis consistently occurred in older patients, in whom renal vascular resistance and nitration fraction were elevated and plasma renin was suppressed. It could not be clarified whether hypernatriuresis together with renin suppression were determined by intrarenal pressure relationships or by an independent age-related factor in the hypertensive patient.

3. Excess of sodium excretion was not related to increments in arterial pressure, cardiac output, renal blood flow or glomerular filtration rate.

4. Plasma renin concentration failed to show consistent changes after hyperosmotic saline infusion.

5. It is concluded that natriuresis is not mediated by changes in the activity of the renin-angiotensin system. Hypernatriuresis appears to be a feature of progressive benign hypertension.
The Effect of Long-Term Mestranol Administration on Calcium and Phosphorus Homeostasis in Oophorectomized Women
Authors: Aitken J. M. , Hart D. McKay , Smith D. A.
Published: August 2015

1. A group of women who had undergone hysterectomy and bilateral salpingooophorectomy were studied and subsequently given either 20–40 μg of mestranol per day or a placebo for 1 year.

2. The administration of mestranol to these oophorectomized women for 1 year was associated with significant falls in serum calcium and phosphorus concentrations, a fall in urinary calcium excretion and a rise in relative urinary phosphorus excretion.

3. It is suggested that these results are consistent with an increase in sensitivity to calcitonin and that the relative hyperphosphaturia reflects a compensatory rise in parathyroid hormone activity.
Leg Blood Flow during Exercise in Man
Authors: Jorfeldt L. , Wahren J.
Published: August 2015

1. An indicator-dilution technique was used to determine human leg blood flow at rest and during exercise. The method is based on the infusion of Indocyanine Green into the femoral artery with blood sampling from the femoral vein at the level of the inguinal ligament. Evidence for mixing of dye and blood is presented, based on the finding of equal dye concentrations at two different sampling levels in the femoral vein. The minimum time of infusion required for equilibration at rest is 3 min and during exercise 1 min 20 s.

2. Leg blood flow was measured in eight healthy athletic subjects at rest and during upright exercise on a bicycle ergometer at 400, 800 and 1200 kpm/min. Linear relationships were found between blood flow on the one hand and work intensity and pulmonary oxygen uptake on the other.

3. Leg oxygen uptake was measured as the product of blood flow and femoral arterio-venous oxygen difference. Linear regressions were found for leg oxygen uptake in relation to both work intensity and pulmonary oxygen uptake. Leg mechanical efficiency during exercise averaged 34%.

4. A formula for the approximate calculation of leg blood flow is suggested, based on the pulmonary oxygen uptake and the femoral arterio-venous oxygen difference.
The Excretion of Salicylate in Salicylate Poisoning
Authors: Morgan A. G. , Polak A.
Published: August 2015

1. The renal clearance of salicylate has been measured in two groups of patients undergoing treatment by alkaline diuresis for salicylate poisoning. One group received mannitol and sodium lactate, the other acetazolamide and sodium bicarbonate.

2. The relationship between urine pH and salicylate clearance was found to be the same in both groups and similar to that shown at non-toxic concentrations in the blood by previous workers.

3. The influence of the rate of urine flow on the relationship between salicylate clearance and urine pH was also shown to be similar to that found at non-toxic concentrations in the blood.
Studies on Acid Excretion in Adults with Sickle-Cell Anaemia
Authors: Kong H. HO Ping , Alleyne G. A. O.
Published: August 2015

1. The acid excretion of patients with sickle-cell anaemia has been studied.

2. There is a mild defect in urinary acidification and a decreased H+ excretion in response to ammonium chloride loading.

3. The acidification defect was not corrected by oral administration of a phosphate solution.

4. Infusion of a sodium sulphate solution in subjects who were avidly reabsorbing sodium produced equal degrees of urine acidification in patients and controls.

5. Studies on bicarbonate reabsorption were inconclusive.

6. We conclude that patients with sickle-cell anaemia have a mild form of incomplete distal renal tubular acidosis.
Studies in Man with 18F
Authors: Hosking D. J. , Chamberlain M. J.
Published: August 2015

1. The distribution of intravenously administered 18F was investigated in thirty-one normal human volunteers, seven patients with acute or chronic renal failure and two patients with malignant disease. The object was to define some features of the bodily distribution and handling of 18F in the hope that this will shed some light on fluoride physiology in health and disease.

2. Plasma radioactivity at any given time depends on the degree of diffusion of 18F through the extracellular fluid as well as on the competing effects of renal excretion and tissue uptake. The factors governing these last two functions are discussed.

3. At 1 h after injection 40% of the administered dose of 18F is contained in the extracellular fluid, 20% has been excreted and 40% taken up by the tissues, including 2·5% into erythrocytes.
Total and Nutritional Blood Flow in the Finger
Authors: Coffman J. D.
Published: August 2015

1. Total and nutritional flow in the fingertip were investigated during reflex sympathetic nerve stimulation (total body cooling) or adrenergic nerve transmitter administration. Nutritional flow was measured by the disappearance rate of a local depot of Na131 I, and total fingertip flow by venous occlusion plethysmography.

2. With body cooling the decrease in nutritional flow was not significant, but total and therefore arteriovenous shunt flow decreased significantly.

3. Norepinephrine infused into the brachial artery decreased total and nutritional flow significantly although total flow decreased more than nutritional.

4. It is concluded that sympathetic nervous system activity exerts a greater effect on finger arteriovenous shunt flow than on nutritional flow. Therefore nutritional flow is not adversely affected.
Distribution and Properties of Na+, K+-ATPase in Human Post-Mortem Kidney and the Effects of Diuretics
Authors: Tulloch B. R. , Gibson K. , Harris P.
Published: August 2015

1. Adenosine triphosphatase activity dependent on Mg2+ and activated by Na+ and K+ has been found in a microsomal fraction of homogenates of human postmortem kidneys.

2. Various characteristics of the enzyme system are described.

3. Activity is greater in the medulla than in the cortex.

4. Diuretic drugs inhibit activity in vitro only at high concentrations.
Observations on the Measurement and Regulation of the Sodium Content of Human Erythrocytes
Authors: Smith E. K. M.
Published: August 2015

1. The sodium concentration within the erythrocytes of 159 subjects was found to be 7·35 ± 1·25 (SD) mmol/litre of cells.

2. In 157 normal subjects, the erythrocyte potassium concentration was 99·08 ± 5·3 (SD) mmol/litre of cells.

3. In the erythrocytes from twenty-seven normal subjects there was a striking linear correlation between the rate constant for active sodium efflux and resting sodium concentration.

4. It is concluded that these studies confirm the assumption that the resting concentration of sodium within a cell is determined by the activity of the sodium pump. What is not known is the mechanism by which this precise control is maintained.
Analysis of Changes in the Renin-Angiotensin System during Pregnancy
Authors: Skinner S. L. , Lumbers Eugenie R. , Symonds E. M.
Published: August 2015

1. Determinations of plasma renin activity (PRA), plasma renin concentration (PRC) and renin substrate (RS) were made on single plasma samples from thirty-four women at various stages of pregnancy. Comparisons were made with non-pregnant control subjects.

2. All three variables were elevated above controls throughout pregnancy, but whereas the mean value of PRA was equally high between the first and the second halves of pregnancy, PRC was higher in the first and RS higher in the second half of pregnancy.

3. Kinetic studies indicated that, in spite of high concentrations of RS in late pregnancy, the renin-renin substrate reaction remains substrate dependent when proceeding at physiological pH values.

4. No differences in enzyme-substrate affinity were detected between the plasmas of pregnant and non-pregnant women.

5. In each of three deliveries RS was lower in the foetus than in the mother but PRA and PRC did not display consistent gradients.

6. PRC in uterine venous blood was slightly lower (P = 0·05) than in peripheral blood during caesarian section at term.

7. On deriving PRC from PRA by using the Michaelis-Menten equation, a physiologically inactive component in maternal PRC became apparent. It is suggested that this component is activated by the acid treatment used in the direct PRC methodology. Its concentration is highest in early pregnancy and circumstantial evidence suggests that it originates from foetal chorion.
The Response of Blood Pressure to Infusion of Angiotensin II: Relation to Plasma Concentrations of Renin and Angiotensin II
Authors: Chinn R. H. , Düsterdieck Gisela
Published: August 2015

1. In thirty-nine normotensive and hypertensive human subjects plasma concentrations of angiotensin II during pressor infusions of the peptide were significantly related to the concentrations found before infusion began.

2. When mean diastolic pressure before and during lower rates of angiotensin infusion were plotted against concurrent plasma angiotensin II concentrations, a straight-line relationship was observed. This relationship also held for the higher rates of infusion in some subjects.

3. During infusion at a standard rate of 4 ng min−1 kg−1 the rise in plasma angiotensin II concentration varied widely from subject to subject.

4. There was a significant negative relationship between this increase and the threshold of the pressor response to angiotensin.

5. There was a significant positive relationship between the threshold of the pressor response and the basal concentrations of renin and angiotensin II.

6. These results suggest that angiotensin normally present in blood lies within or close to a range capable of affecting blood pressure.
Carbon Monoxide, Tissue Hypoxia, and Sensory Psychomotor Response in Hypoxaemic Subjects
Authors: Ramsey J. M.
Published: August 2015

1. Twenty normal subjects, twenty patients with emphysema and twenty with anaemia breathed 0·03% carbon monoxide for 45 min. For all sixty the mean increase in carboxyhaemoglobin (COHb) was 4·5%. Patients with emphysema showed a significantly smaller increase than did the other two groups.

2. The mean decrease in oxygen content was 209 vol./100 ml and was significantly less in patients with emphysema than in the other two groups.

3. All sixty subjects showed a significant diminution in reaction speed to a visual stimulus, but no significant change in tests for depth perception and visual discrimination for brightness.

4. No differences among the three groups were observed in respect to these psychological tests.

5. It is concluded that COHb concentrations of 5% may adversely affect reaction time to visual stimuli and that patients with emphysema are less susceptible to accumulation of COHb and decrease in venous oxygen content than normal subjects or patients with anaemia.
Pathogenesis of Arterial Hypertension after the Constriction of the Renal Artery Leaving the opposite Kidney Intact Both in the Anaesthetized and in the Conscious Dog
Authors: Bianchi G. , Baldoli E. , Lucca R. , Barbin P.
Published: August 2015

1. The renal artery was constricted leaving the opposite kidney intact in ten conscious and seven anaesthetized dogs. Intravenous infusion of exogenous renin was done in seven conscious dogs; in four of these the renal artery was constricted 15–17 days later. The following variables were measured in all animals before and after renal artery constriction: plasma renin concentration, blood pressure, cumulative sodium balance, plasma volume, extracellular fluid volume and plasma non-protein nitrogen. Before and after renal artery constriction in the conscious dogs cardiac output, stroke volume, total peripheral resistance and cardiac rate were also measured. In a few dogs angiotensin responsiveness and plasma concentration of renin substrate were also measured.

2. There was no significant difference between the regression of change in blood pressure on change in plasma renin concentration within 2 h from renal artery constriction in the conscious dogs and that observed during intravenous infusion of renin. Comparing the changes of these variables with the ones previously obtained with renal artery constriction to the lone remaining kidney, for a given increase of plasma renin concentration the rise of blood pressure was lower when the contralateral kidney was untouched. The changes of the other variables in the conscious dogs may be divided into three phases: a first phase lasting hours, in which, besides the changes described above, there was an increase of total peripheral resistance while the other variables remain unchanged: a second phase, 24 h after constriction, in which blood pressure, total peripheral resistance and plasma renin clearance decreased while plasma volume, cardiac output and extracellular fluid volume slightly increased; however, only the plasma volume change was statistically significant: and a third phase 6–7 days after constriction, when all the variables returned towards normal values, except that the blood pressure and total peripheral resistance remained significantly higher. Sodium balance remained at equilibrium throughout the study period. It is suggested that these results are compatible with the ‘autoregulation theory’ of renal hypertension.

3. Renal artery constriction in the anaesthetized animals caused a slight but significant sodium retention that very likely influenced the sequence of the events. On the second day after constriction, the plasma renin concentration was significantly increased, whereas the highest values of blood pressure, plasma volume and extracellular fluid volume occurred on the seventh day after constriction.
Exchangeable Potassium Content and Distribution in Normal Subjects and Uraemic Patients on Chronic Haemodialysis
Authors: Rettori V. , Gral T. , Massry S. G. , Villamil M. F.
Published: August 2015

1. Exchangeable potassium, sulphate space and intracellular fluid have been determined in eight normal males and in seven uraemic male patients on a regime of twice weekly 8 h dialysis.

2. Intracellular water was more closely correlated with exchangeable potassium than were body weight or lean body mass.

3. There was no correlation between exchangeable potassium and plasma or erythrocyte potassium.

4. Uraemic patients had a 20% potassium depletion that may have been due to a restricted oral intake (40 mmol/day) and too little potassium (0–1 mmol/l) in the dialysis fluid.
The Effect of Acute Portacaval Shunting in Dogs on Cerebral and Peripheral Blood Flow and Metabolism
Authors: James I. M. , MacDonell Lindsay , Xanalatos C.
Published: August 2015

1. Changes in brain and hind-limb blood flow and metabolism have been studied in six dogs before and after the acute shunting of portal vein blood into the systemic circulation.

2. An initial increase in brain blood flow, oxygen and glucose consumption was found.

3. More prolonged shunting caused a fall in flow and in oxygen and glucose utilization by the brain.

4. Although peripheral blood flow and oxygen consumption were reduced by shunting glucose consumption was increased throughout the period of shunting.

5. The possible mechanisms of these changes is discussed, together with their relevance to the causation of encephalopathy in patients after portacaval shunts.
Elevation of Alcohol Dehydrogenase Activity in the Subclinically Scorbutic Guinea-Pig
Authors: O'keane Maureen , Moore M. R. , Goldberg A.
Published: August 2015

1. Because it has been shown that a majority of alcoholics are subclinically scorbutic, the metabolism of ethanol was studied in subclinically-scorbutic guinea-pigs.

2. Hepatic alcohol dehydrogenase activity was raised maximally by ethanol within 2 days.

3. In twenty-three subclinically-scorbutic guinea-pigs fed ethanol for 2 weeks, the alcohol dehydrogenase activity (±SD) was 11·5 ± 1·2 units/g of liver protein compared with 8·6 ± 0·6 units/g of liver protein in twenty-three healthy animals fed ethanol.

4. The NAD+/NADH ratio in subclinically-scorbutic guinea-pigs and healthy guinea-pigs fed ethanol, shows that there is more NAD+ available for oxidation of alcohol in subclinically-scorbutic guinea-pigs. These results may explain the increased tolerance of alcoholics to alcohol.
Effect of Exercise on the Renal Clearance of Amylase and Lysozyme in Humans
Authors: Poortmans J. R.
Published: August 2015

1. Total protein amount and amylase and lysozyme activities were measured in the serum and urine of healthy women and men before and after strenuous exercise.

2. Exercise produced no major difference in the serum activities of amylase and lysozyme.

3. The renal clearance of amylase was unaffected by strenuous exercise, but total protein excretion was markedly increased.

4. Very high values of renal clearance of lysozyme were observed after exercise. This implies that the proximal tubular function of protein reabsorption was specifically affected.
The Effect of Sub-Threshold Doses of Pentagastrin on the Acid Response to Insulin in Duodenal Ulcer Subjects before and after Truncal Vagotomy
Authors: Elder J. B. , Gillespie G. , Gillespie I. E. , Crean G. P. , Kay A. W. , Campbell E. H. G.
Published: August 2015

1. On the basis of previously described dose-response curves, small doses of pentagastrin were infused in duodenal ulcer patients before and after vagotomy. No increase or decrease in gastric acid output was noted, confirming that the doses of pentagastrin used were sub-threshold.

2. In twenty-six duodenal ulcer patients the effect of sub-threshold doses of pentagastrin on the insulin response resulted in three distinct patterns. (i) In subjects with clearly functioning vagal pathways, no increase in acid output occurred after insulin when a sub-threshold dose of pentagastrin was added; (ii) patients with equivocal acid responses to insulin alone showed augmentation of acid output when given insulin and a sub-threshold pentagastrin infusion; (iii) patients with no response to insulin after truncal vagotomy showed some increase in acid output to the combined agents, and in two patients, criteria for a clearly positive acid response were satisfied.

3. We conclude from these studies that potentiation exists between insulin-induced cholinergic stimulation and infusion of sub-threshold doses of pentagastrin in man.
Uric Acid in Advanced Renal Failure
Authors: Danovitch G. M. , Weinberger J. , Berlyne G. M.
Published: August 2015

1. The results of studies of renal uric acid excretion in eleven patients with advanced chronic renal failure are presented.

2. The pyrazinamide suppression test was used to separate secretion from reabsorption of uric acid in the renal tubule.

3. There is a marked increase in the excretion and clearance of uric acid as renal function deteriorates. This was due to a striking increase in tubular secretion of urate and to incomplete reabsorption of filtered urate.

4. The remarkable functional capacity of the remaining nephrons of the chronically diseased kidney with respect to uric acid transport might be due to a uricosuric factor in uraemic serum.
The Effect of Caloric Intake on Nitrogen Balance in Chronic Renal Failure
Authors: Hyne B. E. B. , Fowell Edna , Lee H. A.
Published: August 2015

1. Nitrogen balance in uraemic patients on similar nitrogen intakes improves with increasing caloric intake in the range of 36–55 cal/kg body weight.

2. The degree of improvement in nitrogen balance is compatible with increased utilization of endogenous nitrogen probably as a result of increased dietary calories.
Uptake of Dipeptides Containing Basic and Acidic Amino Acids by Rat Small Intestine in Vitro
Authors: Burston D. , Addison Jill M. , Matthews D. M.
Published: August 2015

1. The characteristics of transport and hydrolysis of twenty-two dipeptides containing basic and acidic amino acids by rat ileal rings were investigated in vitro. The peptides included combinations of basic and neutral, basic and basic, basic and acidic, acidic and acidic, and acidic and neutral amino acids.

2. All peptides studied were removed intact from the bulk phase of the incubation medium, though, in general, only free amino acids appeared in the tissue. Uptake of one or both constituent amino acids was greater from the peptide than from the equivalent amino acid or amino acid mixture in the case of at least one peptide from each group and in eighteen of the twenty-two peptides studied. In general, there was no relationship between the extent of uptake of amino acids from peptides and the extent of their hydrolysis by the system. The results support the hypothesis that there is more than one mode of uptake of amino acids from peptides.

3. Hydrolysis of γ-glutamyl-l-glutamic acid by intact intestine or intestinal homogenate was slight, and intact peptide was taken up by the tissue. Uptake of free glutamic acid from this peptide was poor. Comparison of γ-glutamyl-l-glutamic acid with three other slowly hydrolysed dipeptides, glycyl-d-valine, sarcosylglycine and glycylsarcosine, suggested that all four were transported into the mucosal cells and hydrolysed intracellularly. The results indicate that the presence of a γ-linkage or a d-amino acid, or methylation of the free amino group as in sarcosylglycine, impair both transport and hydrolysis of peptide, but that attachment of a methyl group to the N of the peptide bond, as in glycylsarcosine, impairs hydrolysis but has no effect on peptide transport.

4. l-Aspartic acid and l-glutamic acid were extensively transaminated by the intestine, whether presented as free amino acids or in peptides. Evidence was obtained suggesting that production of alanine from aspartic acid resulted from direct transamination of aspartic acid with pyruvic acid, rather than from a sequence of two reactions involving aspartate and alanine aminotransferases.

5. The results show that more rapid uptake of amino acids from peptides than from free amino acids is not confined to peptides made up of neutral amino acids, and probably occurs with many small peptides. Uptake of lysine and the dicarboxylic amino acids, which are particularly slowly absorbed from free solution, was much greater from several dipeptides than from the free amino acids. The results suggest the importance of mucosal peptide uptake in protein absorption.
Humoral Immune Responses in the Tropical-Splenomegaly Syndrome in New Guinea
Authors: Crane G. G. , Rowley Merrill J. , Warburton M. F. , Mackay I. R.
Published: August 2015

1. Humoral immune capacity was measured in New Guineans with tropical splenomegaly or who had been splenectomized for this disease, to assess relationships between tropical splenomegaly and immunological function; the test antigens were flagellin and monovalent influenza vaccine.

2. Controls included age- and sex-matched healthy and hospitalized Caucasians, and comparative data on responses to flagellin were available for New Guinean school children.

3. For flagellin, geometric mean titres in the primary immune response in New Guineans with tropical splenomegaly were significantly lower than those of other groups, whereas pre-immunization titres and those obtained during the secondary response were comparable.

4. For influenza vaccine, both pre-inoculation and peak mean post-inoculation titres of antibody were significantly lower in New Guineans, attributable possibly to lack of previous exposure to this antigen.

5. The low primary antibody responses in New Guineans with tropical splenomegaly could result from pre-emption of antibody-producing tissues arising from abnormal demands for antimalarial antibody; this may determine the increased susceptibility to, and high mortality from, bacterial infection in tropical splenomegaly.
Changes in fat and Carbohydrate Metabolism Caused by Moderate Exercise in Patients with Acromegaly
Authors: Johnson R. H. , Rennie M. J.
Published: August 2015

1. Seven patients with acromegaly and nine controls were studied before, during and after 30 min of moderate steady exercise on a bicycle ergometer. Venous blood samples were taken for estimation of growth hormone (HGH), immunoreactive insulin (IRI), pyruvate, lactate, glucose, free fatty acids (FFA), glycerol and ketone bodies.

2. Exercise caused a rise in HGH concentrations in the acromegalic patients, despite their pituitary tumour, and also in control subjects. Concentrations of IRI fell during exercise in control subjects, but rose in the acromegalic patients.

3. Concentrations of glycerol, FFA and ketone bodies rose rapidly to a maximum during exercise in the acromegalics and appeared to be suppressed before the end of exercise: there was no increase in the concentration of ketone bodies after exercise. In control subjects there was a gradual increase in glycerol and FFA concentrations towards the end of exercise, but no change in ketone bodies occurred until the post-exercise period, when ketone-body concentrations rose.

4. We conclude that exercise causes remarkable differences in metabolite concentrations in the blood of acromegalic patients compared with controls, with the concentration of fat metabolites reaching a maximum, then decreasing during the period of constant exercise. There was also elevation, instead of the normal fall, of plasma IRI activity and it is suggested that the decreased concentration of fat metabolites occurred because of the change of insulin concentration. It is further suggested that in acromegaly insulin retains its effect on re-esterification of fat in spite of resistance to its effects on carbohydrate metabolism.
Plasma Zinc in Pre- and Post-Menopausal Women: Its Relationship to Oestrogen Therapy
Authors: Aitken J. M. , Lindsay R. , Hart D. McKay
Published: August 2015

1. The specific gravity and zinc concentration of plasma obtained during fasting were measured in pre- and post-menopausal women. A number of the latter had been taking 20–40 μg of mestranol daily for at least 1 year.

2. A highly significant correlation was found between plasma zinc concentration and plasma specific gravity in the oophorectomized women who were not receiving oestrogens.

3. The mean plasma zinc concentration was 2 μg/100 ml lower in the pre-menopausal women than in the oophorectomized controls, and this was wholly consistent with the associated fall in plasma specific gravity.

4. The mean plasma zinc concentration in the mestranol-treated women was 12 μg/100 ml lower than that found in the oophorectomized controls, and could not be attributed to the small associated change in plasma specific gravity.

5. It is suggested that the fall in plasma zinc concentration associated with mestranol therapy could be due to either a qualitative change in the plasma proteins or to relative zinc depletion.
Long-Term Variation in Plasma Activities of Aspartate Transaminase and Alkaline Phosphatase in Health
Authors: Levin G. E. , McPherson C. K. , Fraser Patricia M. , Baron D. N.
Published: August 2015

1. Plasma aspartate transaminase and alkaline phosphatase activities were measured weekly for approximately 30 weeks in a group of healthy males and females.

2. The magnitude of variation of the enzyme activities within any individual was studied with respect to four criteria: (a) the individual's normal range, (b) the normal range calculated for each sex separately, (c) the clinically accepted normal ranges, (d) the distribution of a derived term which excluded the variation of the predominant enzyme activities between individuals, and the between-batch variation.

3. The main conclusions were: (a) Normal variation for both these enzymes is small. (b) Most of the variability is contributed by analytical variation. Within-individual variation is very small, this applying particularly to the male subjects' activity of alkaline phosphatase, and the aspartate transaminase activity of female subjects. (c) Elevation of the two enzyme activities above clinical normal ranges was infrequent, never of great magnitude, and occurred almost exclusively in males. When elevations of enzyme activity occurred, they tended to be associated either with particular males, or to occur on certain weeks. (d) When the latter effects were allowed for, and a new set of criteria calculated, the resulting ‘abnormal’ values now appeared to be more randomly distributed.
The Measurement of Bidirectional Sodium Fluxes across the Intestinal Wall in Man Using Whole Gut Perfusion
Authors: Love A. H. G. , Rohde J. E. , Abrams M. E. , Veall N.
Published: August 2015

1. Double-tracer studies have been carried out in order to investigate the validity of a whole-gut perfusion technique for the measurement of gut lumen-to-plasma and plasma-to-gut lumen sodium fluxes in man.

2. The use of two tracers permits differentiation between the unabsorbed orally administered sodium in the stools and the sodium which has been absorbed and resecreted. The latter is by no means negligible and may amount to some 30% of the recovered material.

3. The available data do not permit the calculation of the absolute values of the bidirectional fluxes without the introduction of some assumption concerning the reabsorption of the sodium which crosses from the plasma to the gut lumen. It is assumed here that this sodium is absorbed by the gut to the same extent as the orally administered material. Analysis of the kinetics of sodium transfer from mouth to stool direct and via the blood plasma in normal subjects and patients with diarrhoea provided experimental evidence confirming the correctness of this assumption.

4. In eleven normal volunteers the gut lumen-to-plasma flow of sodium averaged 13.0 mmol min−1, implying that the observed absorption averaging 1.65 mmol min−1 represents a relatively small imbalance between the bidirectional fluxes. Although one patient with post-gastrectomy dumping syndrome had high fluxes and another with malabsorption following gut resection gave low values, it is suggested that changes in the fluxes in the same patient are more significant than isolated observations on individuals.

5. Granted the validity of the primary assumption, a considerably simpler technique may be used for clinical and field studies which is sufficiently accurate for most purposes and employs a single tracer.
Bone Metabolism and Composition in the Protein-Deprived Rat
Authors: Le Roith D. , Pimstone B. L.
Published: August 2015

1. Bone and calcium metabolism in protein-deprived 5-week-old male rats who exhibited no biochemical or histological features of rickets were compared with age-and weight-matched control animals.

2. Intestinal calcium absorption was significantly lower in protein-deprived rats. This was associated with a smaller exchangeable calcium pool and lower bone formation as measured by calcium accretion and proline incorporation into hydroxyproline. However, calcium resorption from bone barely changed in this group and a disproportionately high fraction of the calcium pool continued to be excreted.

3. As a consequence, retarded bone growth occurred in the protein-deprived rat, leading to bones which were shorter and lighter than those of age-matched control animals, the epiphyseal regions appearing to bear the brunt of the growth retardation. This was not accompanied by a change in quality of bone, as the percentage ash content of extirpated bone remained normal.

4. Though alternative hypotheses are possible, the data are consistent with a primary disturbance of intestinal, and possibly renal tubular, calcium transport, perhaps associated with impaired synthesis of calcium-binding protein. An independent depression of collagen synthesis is likely.
Urinary Tamm—Horsfall Glycoprotein in Certain Kidney Diseases and its Content in Renal and Bladder Calculi
Authors: Grant Anne M. S. , Baker L. R. I. , Neuberger A.
Published: August 2015

1. Tamm—Horsfall (T—H) glycoprotein has been measured by a specific radioimmunoassay method in the urine of patients with chronic renal failure, cadmium nephropathy and Lignac—Fanconi syndrome, and in renal and bladder calculi.

2. Total T—H glycoprotein excretion/24 h was markedly reduced in patients with chronic renal failure compared with normals. A highly significant correlation was observed between T—H excretion rate and creatinine clearance corrected for surface area, in both normals and patients with renal impairment. However, the mean T—H excretion per functioning nephron unit did not differ significantly in patients with renal failure compared with normals.

3. Total T—H excretion/24 h was in the normal range in patients with cadmium nephropathy despite reduced glomerular filtration rates, owing to a highly significant increase in T—H excretion per functioning nephron unit. Similar findings were obtained in a group of children with Lignac—Fanconi syndrome whose T—H excretion per functioning nephron unit was much higher than that of normal children in the same age range. This indicates an increased T—H glycoprotein excretion per functioning nephron unit in both these conditions.

4. T—H glycoprotein content of bladder and renal calculi ranged from 0002 to 5.07 mg/g of calculus. There was no correlation between T—H glycoprotein content and either the total protein content or the qualitative inorganic composition of the stones.
Two Sites of Cardiovascular Action of Angiotensin II in the Brain of the Dog
Authors: Gildenberg P. L. , Ferrario C. M. , McCubbin J. W.
Published: August 2015

1. Infusion of angiotensin into both vertebral arteries or into a lateral cerebral ventricle of dogs anaesthetized with morphine-chloralose elicited a centrally mediated rise in blood pressure.

2. Heat coagulation of the area postrema and immediately adjacent structures abolished the pressor response to infusion of angiotensin into the circulation of the vertebral arteries, but did not alter the pressor response when the peptide was delivered into a cerebral lateral ventricle; transection of the midbrain eliminated the latter response but not the former.

3. It is concluded that there are at least two areas in the dog's brain that respond to angiotensin by inducing a raised blood pressure.
Impairment of Phenylalanine Hydroxylation in Chronic Renal Insufficiency
Authors: Young G. A. , Parsons F. M.
Published: August 2015

1. Plasma tyrosine and phenylalanine were measured in patients with chronic renal failure and in normal subjects. Plasma tyrosine to phenylalanine ratio was greatly decreased in patients with creatinine clearance less than 16 ml/min, suggesting an impairment of phenylalanine hydroxylation. This ratio correlated with the percentage of essential to total amino nitrogen in the plasma.

2. Phenylalanine hydroxylase from rat liver was inhibited or inactivated (15%) by uraemic plasma but this could not be attributed to the individual effects of urea, creatinine, uric acid, oxalic acid, phenylpyruvic acid, glycine or phosphate. It is unlikely that the degree of inhibition was sufficient to account for the impairment of phenylalanine hydroxylation in chronic renal insufficiency.

3. Phenylalanine hydroxylase was present in rat kidney but at a very low activity relative to that present in liver; consequently, the loss of functional kidney tissue associated with chronic renal insufficiency is unlikely to impair phenylalanine hydroxylation.

4. Plasma tyrosine and liver phenylalanine hydroxylase activity were significantly decreased in partially nephrectomized rats when protein intake was inadequate.
Intestinal Absorption of Stereoisomers of Dipeptides in the Rat
Authors: Asatoor A. M. , Chadha Amrit , Milne M. D. , Prosser D. I.
Published: August 2015

1. Studies have been made of jejunal absorption rates in vivo in the rat of the stereoisomers of alanylphenylalanine, leucyl-leucine and glycyltryptophan. Absorption rates of l-alanyl-l-phenylalanine were about 200 times those of d-alanyl-d-phenylalanine, l-leucyl-l-leucine about 24 times those of the dd-isomer, and glycyl-l-tryptophan 5 times those of glycyl-d-tryptophan. The mixed ld- and ld-isomers were absorbed at intermediate rates.

2. Absorption rates were positively correlated with the rate of hydrolysis of each dipeptide by homogenates of rat intestinal mucosa. The transport rate and rate of hydrolysis of glycyl-d-tryptophan, d-alanyl-d-phenylalanine and d-leucyl-d-leucine were significantly greater in the ileum than in the jejunum.

3. When given by stomach tube the most slowly absorbed dipeptides, d-alanyl-d- phenylalanine, d-leucyl-d-leucine and glycyl-d-tryptophan were the only ones to be excreted in significant amounts in the urine, showing that they were absorbed as the entire molecule and were resistant to hydrolysis by tissue peptidases.

4. There was a close inverse correlation between the rates of transport by rat jejunum of glycine, d-alanine, d-leucine, d-phenylalanine, d-tryptophan, d-alanyl-d- phenylalanine, d-leucyl-d-leucine and glycyl-d-tryptophan and the molecular weight of each compound, suggesting that diffusion mechanisms play an appreciable part in jejunal absorption of these compounds. No such correlation was found in the case of the ileum.