bluuebunny/crossref_metadata_2025 huggingface dataset:
Renal Salt and Water Handling in Water Immersion in the Nephrotic Syndrome
Authors: Berlyne G. M. , Sutton J. , Brown C. , Feinroth M. V. , Feinroth M. , Adler A. J. , Friedman E. A.
Published: August 2015

1. Eleven nephrotic patients were immersed up to the neck in 1.3 m of water at 34°C for 4 h.

2. A diuresis began, within the first hour of, and continued throughout, immersion. The urine osmolality fell significantly and decreased to hypotonic levels in the first hour of immersion and increased gradually during the remainder of immersion and postimmersion.

3. Throughout immersion there was a steady increase in urinary sodium and chloride excretion and a sharp fall in the postimmersion hour.

4. Overall fractional excretion of sodium and of chloride increased steadily throughout immersion and fell during the post-immersion hour.

5. There was an increase in urinary potassium excretion on immersion but no change in fractional excretion of potassium. There was an initial increase in distally reabsorbed sodium/chloride on immersion, as expressed by positive values of CH2O in the first hour of immersion.

6. Plasma aldosterone levels were initially elevated in only two out of nine patients. There was a significant fall in plasma aldosterone levels on immersion, but there was no correlation between sodium/chloride handling and aldosterone levels on immersion.
Effects of Thyroparathyroidectomy, Phosphate Depletion and Diphosphonate Therapy on Acute Uraemic Extra-Osseous Calcification in the Rat
Authors: Ibels L. S. , Alfrey A. C.
Published: August 2015

1. The effects of acute uraemia on arterial and visceral calcium concentrations were studied in acutely uraemic rats. The influences of thyroparathyroidectomy, phosphate depletion and diphosphonate therapy on extra-osseous calcium concentrations were assessed in this model.

2. Aortic and visceral calcium concentrations were greater in acutely uraemic rats than in non-uraemic rats. Both prior thyroparathyroidectomy and prior phosphate-depletion resulted in lower aortic and visceral calcium concentrations in non-uraemic rats and prevented the increase in aortic and visceral calcium concentrations with acute uraemia. Diphosphonate given for 5 days before and for 2 days after the induction of acute uraemia resulted in lower tissue calcium concentrations than in non-diphosphonate-treated acutely uraemic rats. In contrast, diphosphonate given only immediately before or only after induction of acute uraemia did not prevent the increase in extra-osseous calcium concentrations with acute uraemia.

3. It is concluded that acute uraemia results in an increase in arterial and visceral calcium concentrations. Both thyroparathyroidectomy and phosphate depletion are effective in preventing the increase in extra-osseous calcium concentrations in acute uraemia. Diphosphonates may have a future role in preventing such calcification.
Body Fluid Volumes in the Spontaneously Hypertensive Rat
Authors: Bianchi M. , Bellini G. , Hessan H. , Kim K. E. , Swartz C. , Fernandes M.
Published: August 2015

1. Plasma volume, packed cell volume (PCV), blood volume, extracellular fluid volume (ECFV) and Evans blue disappearance rate were measured in conscious spontaneously hypertensive rats and in weight-matched Wistar normotensive rats.

2. Over the weight range studied (250-350 g), plasma and blood volumes were significantly lower in the spontaneously hypertensive rat. Extracellular fluid volumes were similar in the two groups. PCV arid Evans blue disappearance rates were significantly higher in the spontaneously hypertensive rat.

3. Negative correlations were obtained between plasma volume and mean arterial pressure and between the plasma/interstitial fluid volume ratio and mean arterial pressure.

4. the normal extracellular fluid volume and the lack of correlation with mean arterial pressure excludes volume expansion as a pressor mechanism during the established phase of hypertension in the spontaneously hypertensive rat.
Respiratory Arterial PH and P
co2 Oscillations in Patients with Chronic Obstructive Airways Disease
Authors: Cochrane G. M. , Prior J. G. , Wolff C. B.
Published: August 2015

1. Arterial pH oscillations have been monitored in vivo in patients with well defined chronic obstructive bronchitis, asthma and clinical emphysema.

2. the patients with clinical emphysema were shown to differ from those with chronic obstructive bronchitis on the basis of a number of clinical and physiological criteria.

3. Patients with asthma showed least attenuation of their pH oscillations as a group, in contrast to emphysematous patients who showed most attenuation. in patients with clinical emphysema the attenuation was relatively homogeneous. the patients with chronic obstructive bronchitis showed the full range from normal oscillations (zero attenuation) to zero (complete attenuation).

4. the amplitude and approximate rate of change of upslope of the Paco2 oscillations in vivo were calculated, from measured pH oscillation amplitudes, using buffer slope values in vitro from Siggaard Anderson [(1962, 1963) Scandinavian Journal of Clinical and Laboratory Investigation, 14, 598–604; 15, 211–217], then dividing the Paco2 amplitude by half the respiratory period.

5. Mean arterial Pco2in vitro showed a very strong correlation with the downslope of the pH oscillation in vivo (calculated as for Paco2 upslope) in patients without clinical emphysema. This correlation would be expected to some extent, owing to the logarithmic relationship of Paco2 oscillations to pH oscillations. However, the mean arterial Pco2 also showed a very strong correlation with the upslope of the calculated Paco2 oscillations, again excluding patients with clinical emphysema.
Blood Pressure and Plasma Sodium and Potassium
Authors: Bulpitt C. J. , Shipley M. J. , Semmence A.
Published: August 2015

1. Two thousand, three hundred and twenty-eight men and 1496 women between the ages of 35 and 64 years were screened for hypertension and their plasma sodium and potassium concentrations measured. Those on antihypertensive or diuretic treatment were excluded from further analysis.

2. After adjusting for age, body mass index and other variables, plasma potassium was negatively associated with both systolic and diastolic pressure in men and women. A decrease in plasma potassium of 1 mmol/l was associated with an increase in systolic pressure in women of 7 mmHg (P < 0.001) and diastolic pressure of 4 mmHg (P < 0.001). In men the corresponding increases were 4 mmHg (P < 0.01) and 2 mmHg (P < 0.05).

3. After adjusting for the other variables as above, plasma sodium was positively related to systolic blood pressure but not to diastolic pressure. An increase in plasma sodium of 1 mmol/l was associated with an increase in systolic pressure of 1 mmHg in both men (P < 0.01) and women (P < 0.05).
Factors Influencing Cardiac Hypertrophy in Hypertensive Patients
Authors: Ibrahim M. Mohsen , Madkour M. Aziz , Mossallam Ragaa
Published: August 2015

1. Seventeen male patients with essential hypertension were studied after 4 weeks of placebo and after 8 weeks of β-adrenoceptor-blockade therapy with atenolol (100 mg/day).

2. The influence of the following factors on left ventricular wall thickness and left ventricular mass index as determined by echocardiography was examined: patient's age, duration of hypertension, arterial pressure, blood pressure variability, supine heart rate, maximal exercise heart rate, left ventricular wall stress and 24 h urinary catecholamines.

3. Left ventricular mass index was related to systolic blood pressure (r = 0.54, P < 0.05) and to extent of increase in heart rate with maximal exercise (r = 0.62, P < 0.05). No significant correlation was present between mass index and other variables.

4. After atenolol therapy, left ventricular mass index decreased by 14 g/m2 (12%). Changes in mass were related to its initial value (r = 0.69, P < 0.01) and to% change in wall stress (r = 0.64, P < 0.05). Patients who had a decrease in mass index of 10% or greater had an initially lower diastolic pressure (P < 0.001). Other factors did not appear to influence significantly the regression of hypertensive left ventricular hypertrophy.
Haemodynamic Changes after Surgical Reversal of Chronic Two-Kidney, One-Clip Hypertension in the Rat
Authors: Russell G. I. , Brice J. M. , Bing R. F. , Swales J. D. , Thurston H.
Published: August 2015

1. Within 24 h of surgical reversal of chronic Goldblatt two-kidney, one-clip hypertension in the rat, of >4 months duration, blood pressure had fallen to normal levels. At this time there was no difference between the effects of removal of the clip or the ischaemic kidney but, at 60 days after reversal, the blood pressure of rats which had been nephrectomized was significantly higher than that of normal controls.

2. The fall in blood pressure was associated with a fall in total peripheral resistance to normal by 24 h despite the previous established fact that structural vascular changes take much longer to reverse. There was a corresponding rise in cardiac output, mainly due to an increase in stroke volume. Nephrectomized rats had a significantly higher stroke volume compared with those unclipped 24 h after operation.

3. As blood pressure can become normal in the presence of structural cardiovascular change by a fall in total peripheral resistance it would seem unlikely that resistance vessel hypertrophy is responsible for the maintenance of blood pressure in this model. Another peripherally acting mechanism therefore has to be postulated.
Plasma Noradrenaline as a Measure of Baroreflex Sensitivity in Hypertensive Man
Authors: Shepherd A. M. M. , Lin M.-S. , Keeton T. K. , McNay J. L.
Published: August 2015

1. Changes in plasma noradrenaline levels and heart rate were used as measures of baroreflex sensitivity in six hypertensive subjects given serial incremental doses of sodium nitroprusside (intravenously) to lower blood pressure.

2. The rises in both heart rate and plasma noradrenaline concentration were linearly related to the decrement in blood pressure and inversely related to the severity of the hypertension.

3. A positive correlation between rise in heart rate and rise in plasma noradrenaline was found for each subject. With increasing severity of hypertension, a greater increase in heart rate occurred for each increment in plasma noradrenaline concentration.

4. Baroreflex sensitivity can be assessed by relating changes in heart rate to change in arterial pressure; however, this method does not distinguish the relative contributions of the vagal and sympathetic components of the autonomic neural response or variations in the chronotropic response to sympathetic stimulation.

5. Changes in plasma noradrenaline levels in response to graded reductions in blood pressure may be a more appropriate measure of baroreflex sensitivity than the methods currently used in clinical investigation.
A Sympathetic Hypertensive Reflex from the Heart of Conscious Dogs
Authors: Pagani M. , Pizzinelli P. , Furlan R. , Guzzetti S. , Rimoldi O. , Malliani A.
Published: August 2015

1. The aim of the present experiments was to study in conscious animals the effect of chemical stimulation of cardiac sensory innervation by bradykinin, a physiological substance known to activate both vagal and sympathetic cardiac sensory nerve endings, at doses devoid of systemic haemodynamic effects.

2. In conscious dogs with implanted catheters bradykinin (100 ng/kg) injected into a cannulated branch of the left coronary artery induced significant (P < 0.01, n = 5) reflex increases in mean arterial pressure and heart rate as well as increases in left ventricular pressure, left ventricular dP/dt max. and coronary blood flow.

3. These changes were obtained in the absence of pain reactions.

4. The concept, derived from experiments on anaesthetized animals, that chemical stimulation of the intact sensory supply of the heart always elicits a cardiovascular depressor reflex mediated by cardiac vagal afferents has to be modified, as pressor sympathetic reflexes may occur after an appropriate stimulus to the fully innervated heart of conscious dogs.
Adrenergic Components of Hypertension after Renal Transplantation
Authors: Smith R. S. , Reid J. L. , Warren D. J.
Published: August 2015

1. Blood volume, total exchangeable sodium and the effects of head-up tilt on plasma noradrenaline were studied in 10 normotensive and 11 hypertensive renal transplant recipients. The blood pressure and heart rate responses to infused noradrenaline and isoprenaline were measured.

2. Blood volume and total exchangeable sodium were significantly greater in hypertensive than in normotensive patients.

3. Resting plasma noradrenaline was significantly higher in both groups of transplantees than in normal subjects, but was similar in normotensive and hypertensive patients.

4. Plasma noradrenaline rose in normotensive but not hypertensive patients in response to head-up tilt.

5. The rise in blood pressure in response to infused noradrenaline was significantly greater in hypertensive than in normotensive transplantees. Both groups of patients showed similar responses to infused isoprenaline.

6. Extracellular fluid volume expansion associated with increased α-receptor sensitivity to noradrenaline may contribute to hypertension in renal transplant recipients.
Blood Pressure, Renal and Metabolic Effects of ACTH in Normotensive Man
Authors: Whitworth Judith A. , Saines Dianne , Thatcher Robyn , Butkus Aldona , Scoggins B. A. , Coghlan J. P.
Published: August 2015

1. The blood pressure, renal and metabolic effects of adrenocorticotropic hormone (ACTH) have been studied in six normotensive subjects and two patients with Addison's disease on maintenance steroid therapy.

2. In normotensive subjects, 5 days ACTH treatment (0.5 mg 12 hourly) was associated with a rise in systolic blood pressure and mean arterial pressure. There was a small rise in diastolic pressure but no consistent change in heart rate. Plasma sodium increased and plasma potassium fell. Serum creatinine and urea concentrations were unchanged. Fluid intake increased and urine output was unchanged but ACTH withdrawal was associated with a diuresis. There was an initial reduction in urinary sodium excretion and a natriuresis after ACTH withdrawal. Plasma volume and body weight rose.

3. ACTH produced increases in plasma cortisol, 11-deoxycortisol, corticosterone, deoxycorticosterone, aldosterone, 17α-hydroxyprogesterone and 17α,20α-dihydroxyprogesterone. Plasma renin concentration fell.

4. Patients with Addison's disease showed no change in blood pressure or in any other metabolic variable studied.

5. The effects of ACTH in man resembled those found in sheep.
Hypertension, Cerebrovascular Disease and Stomach Cancer: Is the Salt Hypothesis True?
Authors: Whelton Paul K. , Goldblatt Peter
Published: August 2015

1. Analysis of age-adjusted death rates from 21 countries over a 20-year period identified the presence of a strong positive association between recorded mortality from stroke, hypertension and stomach cancer. However, the slopes of regression lines for secular trends analyses varied considerably from country to country, suggesting an inconsistency in the pattern of the relationship.

2. A death certificate study of diagnostic concordance correctly identified previously known disease associations but failed to recognise any special relationship between stroke and stomach cancer or hypertension and stomach cancer.

3. Our results fail to confirm the presence of a unique relationship between stroke and stomach cancer. On the basis of these observations, the hypothesis that exposure to salt increases an individual's risk of developing both stroke and stomach cancer seems unlikely.
The Influence of Chronic High Alcohol Intake on Blood Pressure, Plasma Noradrenaline Concentration and Plasma Renin Concentration
Authors: Ibsen H. , Christensen N. J. , Rasmussen S. , Hollnagel Hanne , Nielsen M. Damkjaer , Giese J.
Published: August 2015

1. Sixteen 44-year-old males with chronic high alcohol intake were investigated. Seventeen 44-year-old males with low alcohol intake from the same population served as controls.

2. Plasma noradrenaline concentrations did not differ significantly between individuals with high and low alcohol intake, neither at rest nor after acute stimulation induced by ambulation for 15 min. However, 63% (10 out of 16) of the individuals with high intake showed resting values within the upper quartile range for individuals with low intake.

3. Plasma renin concentration was twice as high (P < 0.01) in the group with high alcohol intake as in the group with low intake.

4. Systolic as well as diastolic blood pressure was significantly higher (P < 0.01) in the group with high intake compared with the group with low intake.

5. Sympathetic nerve activity, as defined from measurements of plasma noradrenaline concentration, is not uniformly increased in individuals with chronic high alcohol intake. The mechanisms behind the increased plasma renin level as well as the possible role of the renin-angiotensin system in alcohol-induced hypertension remain unsettled.
Prizidilol (SKF 92 657) in Primary Hypertension
Authors: Karlberg B. E. , Larsson R. , öhman K. P.
Published: August 2015

1. Prizidilol (SKF 92 657), a new antihypertensive drug with combined precapillary vasodilator and non-selective β-adrenoceptor-blocking actions, was given to 24 patients with essential hypertension in a placebo-controlled, dose-titration study, Incremental doses from 200 to 800 mg were given once daily. Supine and standing blood pressure measured 24–27 h after drug intake was reduced during treatment with prizidilol (400–800 mg/day). Slight but significant decreases in heart rate were seen after moderate doses (mean: 447 mg once daily) of prizidilol. A more pronounced blood pressure reduction was noticed 2–7 h after drug administration.

2. Maximal blood pressure reduction coincided with peak plasma concentration of prizidilol, which was measured by a newly developed assay.

3. Plasma renin activity and 24 h urinary excretion of aldosterone and methoxycatecholamines were reduced after the highest doses (mean: 700 mg once daily) of prizidilol.

4. Prizidilol was well tolerated, although dizziness and tiredness were reported by four patients and oedema by two.
The Antihypertensive Effects of Ketanserin (R 41 468), a Novel 5-Hydroxytryptamine-Blocking Agent, in Patients with Essential Hypertension
Authors: De Crée J. , Leempoels J. , Geukens H. , De Cock W. , Verhaegen H.
Published: August 2015

1. In a double-blind placebo-controlled crossover study a 4 week treatment with ketanserin was shown to reduce systolic and diastolic blood pressure markedly and significantly in 10 patients with essential hypertension. Heart rate remained virtually unchanged during the whole observation period. Systolic time intervals, reflecting cardiac output, did not change during the ketanserin phase, whereas these values deteriorated during the placebo period.

2. Ketanserin, a novel 5-hydroxytryptamine (5HT2)-receptor antagonist with a high selectivity for blood vessels and thrombocytes, most probably acts by decreasing the venous capacitance bed constriction, and by counteraction of the amplifying effects of serotonin on noradrenaline and other vasoactive amines.
Percutaneous Transluminal Dilatation of Renal Artery Stenosis: 2 years' Experience
Authors: Kuhlmann U. , Vetter W. , Grüntzig A. , Schneider E. , Pouliadis G. , Steurer J. , Siegenthaler W.
Published: August 2015

1. Percutaneous transluminal dilatation was performed in 37 patients with renovascular hypertension: 24 had atherosclerotic renal artery stenosis and 13 had fibromuscular dysplasia.

2. Percutaneous transluminal dilatation could not be performed for technical reasons in three (8%) of the 37 patients.

3. In the remaining 34 patients blood pressure fell significantly (P < 0.001) from 201 ± 31/118 ± 14 mmHg to 144 ± 22/91 ± 11 mmHg 3 days after the procedure. The respective values at months 6 and 24 were 148 ± 26/89 ± 12 mmHg (n = 23, P < 0.001) and 143 ± 14/89 ± 6 mmHg (n = 8, P < 0.001).

4. Certain differences between the two subgroups emerged in the response to percutaneous transluminal dilatation (6 months values, n = 23): cure rate was higher in patients with fibromuscular dysplasia than in those with atherosclerotic stenosis (67% vs 35%) and in contrast to atherosclerotic stenosis none of the cases with fibromuscular dysplasia was unimproved.

5. Follow-up angiography performed at month 6 showed recurrence of slight renal artery stenosis in five out of 19 patients (all atherosclerotic).

6. Complications were seen in six (16%) of the 37 patients.

7. Our results show that percutaneous transluminal dilatation is a valid method for the treatment of renovascular hypertension. Patients with fibromuscular dysplasia may show a better response than those with atherosclerotic stenosis. In this study the latter was complicated by a high risk of developing restenosis. Finally a complication rate of 16% requires careful selection of patients.
Synovial Fluid and Plasma Fibronectin Levels in Rheumatoid Arthritis
Authors: Scott D. L. , Farr M. , Crockson A. P. , Walton K. W.
Published: August 2015

1. Plasma fibronectin levels were similar in 60 healthy subjects and 88 with rheumatoid arthritis.

2. In 42 patients with rheumatoid arthritis synovial fluid fibronectin levels were significantly higher than plasma levels (P < 0.001). Intermediate fibronectin levels were found in synovial fluid from six patients with psoriatic arthritis, eight patients with osteoarthritis and seven with seronegative arthritis.

3. Plasma and synovial fluid fibronectin levels were not related to indices of inflammatory activity such as the erythrocyte sedimentation rate, the Ritchie articular index or synovial fluid cell counts. Nor did fibronectin behave as an acute-phase protein.

4. Immunofluorescent studies showed that fibronectin was adsorbed on fibrinous debris in rheumatoid arthritic joints.

5. These findings suggest that there is local production of fibronectin by the synovium and suggest that measurement of fibronectin levels in the synovial fluid may serve as an indicator of the tissue response to rheumatoid arthritis.
β-Adrenoceptor Blockade and Recovery from Hypoglycaemia in Diabetic Subjects: Normalization after Lactate and Glycerol Infusions
Authors: Lager I. , Smith U.
Published: August 2015

1. Previous studies have shown that non-selective β-adrenoceptor blockade attenuates the blood glucose recovery rate after hypoglycaemia in type I diabetes. Apart from possible effects on hepatic glycogenolysis propranolol also inhibits the release of the important gluconeogenic substrates lactate and glycerol.

2. To determine whether the effect of non-selective β-adrenoceptor blockade on glucose recovery could be associated with diminished availability of gluconeogenic substrates, lactate and glycerol were infused during hypoglycaemia in four insulin-dependent diabetic patients. Comparisons were made of the blood glucose recovery on placebo, propranolol and propranolol combined with the infusion.

3. The blood glucose recovery rate after hypoglycaemia was less on propranolol than with placebo but was significantly improved and not different from placebo when propranolol treatment was combined with lactate and glycerol infusions. Thus, at least for type I diabetic patients, in whom gluconeogenesis is proportionally greater than in healthy subjects, non-selective β-adrenoceptor blockade attenuates the glucose recovery rate from hypoglycaemia mainly by reducing the availability of gluconeogenic substrates.
Influence of the Vagus Nerve on Changes in Heart Rate during Sleep Apnoea in Man
Authors: Meanock C. I.
Published: August 2015

1. The changes in heart rate surrounding a period of apnoeic asphyxia, produced by either central or obstructive sleep apnoea, are characteristically a progressive bradycardia during the apnoeic period followed by an abrupt reversal to tachycardia with resumption of lung inflation.

2. In a subject who had undergone bilateral pulmonary vagotomy with sparing of the cardiac branches on the left side, the bradycardia is still present during the apnoeic period; however, there is no abrupt response to lung inflation.

3. A subject who had undergone unilateral right-sided pulmonary vagotomy demonstrated a normal response, the increase in heart rate coinciding with resumption of airflow.

4. These findings are consistent with the hypothesis that the bradycardia of sleep apnoea is a hypoxia-induced chemoreflex and that reversal to tachycardia with resumption of lung inflation is a reflex with afferent fibres in the pulmonary vagus nerves.
Alterations in Haem Biosynthesis during the Human Menstrual Cycle: Studies in Normal Subjects and Patients with Latent and Active Acute Intermittent Porphyria
Authors: McColl K. E. L. , Wallace A. M. , Moore M. R. , Thompson G. G. , Goldberg A.
Published: August 2015

1. The timing of onset of attacks of acute intermittent porphyria (AIP) in relation to the menstrual cycle has been studied in three patients experiencing frequent attacks. Nineteen of their 27 admissions in attack for which no exogenous precipitating causes could be identified were during the 7 days before the onset of menstruation.

2. Haem biosynthesis has been monitored throughout a complete menstrual cycle in six normal females and compared with that in male control subjects. In the females, there was marked fluctuation in the activity of the rate-controlling enzyme of haem biosynthesis, δ-aminolaevulinate (ALA) synthase, which was monitored in peripheral leucocytes. The fluctuation did not show any clear association with menstruation and no association was found between the enzyme activity and ovarian or adrenal steroid production as monitored by measurement of plasma concentrations of androstenedione, dehydroepiandrosterone (DHA), dehydroepiandrosterone sulphate (DHAS), testosterone, oestradiol and progesterone. The activity of uroporphyrinogen I (URO) synthase, the enzyme which is deficient in AIP, was monitored in peripheral erythrocytes of four of the normal female subjects and was similar to that found in four male control subjects. The urinary excretion of ALA and porphobilinogen (PBG) was also similar in the male and female subjects and there was no association with the phase of the menstrual cycle or activity of the enzymes studied.

3. Studies of haem biosynthesis have been made throughout a complete menstrual cycle in a 26 year old female with latent AIP. The activity of leucocyte ALA synthase showed more marked fluctuation than in the normal female subjects and was highest at the time of menstruation. No association was apparent between the activity of ALA synthase and plasma concentrations of androstenedione, DHA and DHAS. The fluctuation in activity of erthrocyte URO synthase was similar to that of the normal subjects. The urinary excretion of ALA and PBG was normal throughout and showed no correlation with fluctuations in enzyme activity.

4. The human menstrual cycle modifies haem biosynthesis in normal subjects as well as in subjects with latent and manifested AIP.

5. The human female menstrual cycle modifies haem biosynthesis in peripheral blood cells as well as in the liver.
Is the Pro-Adhesive Activity of Plasma Von Willebrand Factor Counteracted by a Physiological Inhibitor of Platelet Adhesiveness?
Authors: Porta M. , Cagliero E. , Kohner E. M.
Published: August 2015

1. Abnormal plasma levels of von Willebrand factor are accompanied by abnormal platelet function in some disease states.

2. Platelet retention in glass bead columns, platelet aggregation in vitro, β-thromboglobulin and 6-oxo-prostaglandin F1α were monitored in six normal male volunteers before and after an acute rise of von Willebrand factor, as induced by the intravenous administration of 1-deamino-8-d-arginine vasopressin (DDAVP).

3. After DDAVP a steady twofold rise of von Willebrand factor occurred. Platelet retention increased by 74% immediately after DDAVP but returned to baseline values within 60–120 min. No consistent changes of the other variables were observed.

4. These results suggest that as yet unidentified mechanism(s) inhibits the pro-adhesive activity of von Willebrand factor.
Total Hepatectomy and Hepatic Vascular Exclusion in the Rat: A Comparison, with Special Reference to the Influence of Body Temperature
Authors: Peignoux M. , Bernuau J. , Benhamou J.-P.
Published: August 2015

1. The effects of two procedures for dehepatization, total hepatectomy and complete hepatic vascular exclusion, were compared in the rat, and the influence of decreasing the body temperature from 37.5° to 35.5°C on the course of dehepatization was evaluated.

2. The duration of survival after total hepatectomy was 5.75 ± sd 0.67 h at 37.5°C and 8.51 ± 0.78 h at 35.5°C (P < 0.001). The duration of survival after complete hepatic vascular exclusion was 5.61 ± 1.06 h at 37.5°C and 8.30 ± 0.70 h at 35.5°C (P < 0.001).

3. It is concluded that (a) the duration of survival does not differ after total hepatectomy and after complete vascular exclusion, which suggests that substances released by the necrotic liver have no influence on the course of dehepatization, and (b) the body temperature has an influence on the course of dehepatization and must be carefully monitored in the comparison of the different procedures for dehepatization and in the assessment of experimental therapeutic methods for acute liver failure.
Relationship between Hepatic Cholesterol Synthesis and Biliary Cholesterol Secretion in Man: Hepatic Cholesterol Synthesis is not a Major Regulator of Biliary Lipid Secretion
Authors: Maton P. N. , Reuben A. , Dowling R. H.
Published: August 2015

1. To examine the role of newly synthesized cholesterol as a determinant of bile lipid secretion, both hepatic cholesterol synthesis (as judged by the activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, EC 1.1.1.34; HMGCoAR) and steady state biliary cholesterol output were measured in nine patients.

2. HMGCoAR levels varied four fold (9–40 pmol min−1 mg−1) and biliary cholesterol secretion 2–5-fold (0.60−1.15 μUmol h−1 kg−1) but there was no correlation between these two variables (r = 0.18; P>0.05) nor between biliary bile acid output and HMGCoAR activity (r = 0.34; P>0.05).

3. There was, however, a linear relationship between bile acid and phospholipid secretion (r = 0.77; P<0.001) and between bile acid and cholesterol secretion (r = 0.69; P<0.05).

4. These results suggest that HMGCoAR activity is not a major determinant of cholesterol secretion nor at these secretion rates is HMGCoAR activity related to bile acid return to the liver.
The Autonomic Nervous Tone Abnormalities in the Genesis of the Impaired Baroreflex Responsiveness in Borderline Hypertensive Subjects
Authors: Volpe Massimo , Trimarcoy Bruno , Ricciardelli Bruno , Vigorito Carlo , De Luca Nicola , Rengo Franco , Condorelli Mario
Published: August 2015

1. The effects of intravenous administration of neostigmine and propranolol, individually or in combination, on baroreflex responsiveness have been evaluated in 18 borderline hypertensive subjects and in 14 age-matched control subjects.

2. Baroreceptor sensitivity was tested by evaluating both heart rate response to phenylephrine-induced increase in arterial pressure, and heart rate and blood pressure changes induced by increasing neck-tissue pressure by means of a neck-chamber.

3. In borderline hypertensive subjects a reduced baroreflex responsiveness was demonstrated with both stimuli as compared with normal subjects. Neostigmine administration improved consistently both reflex responses. Similarly, after propranolol treatment, borderline hypertensive subjects showed a significant enhancement of the baroreflex sensitivity. Finally, the combined administration of neostigmine and propranolol restored the baroreflex responses. In fact, both the mean slopes of the regression lines between blood pressure and R-R interval after phenylephrine and the increase in mean arterial pressure and heart rate induced by the reduction in carotid transmural pressure in borderline hypertensive subjects were similar to those observed in normals.

4. These findings indicate that in borderline hypertensive subjects the impairment of baroreflex responsiveness is mainly due to abnormalities of autonomic regulation.
Duodenal Perfusion with Sodium Taurocholate Inhibits Biliary but not Pancreatic Secretion in Man
Authors: Björnsson Ó. G. , Fletcher D. R. , Christofides N. D. , Bloom S. R. , Chadwick V. S.
Published: August 2015

1. A standard duodenal perfusion technique was used to study the effects of luminally perfused sodium taurocholate on basal and stimulated biliary and pancreatic secretion and gastrointestinal hormone release in man.

2. During duodenal perfusion with sodium taurocholate alone, both basal and caerulein/secretin-stimulated bilirubin secretion were suppressed. A successive perfusion with a mixture of the bile salt and essential amino acids in combination overcame the biliary suppression and biliary secretion rose above basal levels. A further increase in bilirubin secretion was not observed in a subsequent perfusion with essential amino acids alone in these studies.

3. No inhibitory effect on basal or caerulein/secretin-stimulated trypsin secretion was observed during the bile salt perfusion; basal trypsin secretion was in fact slightly increased during a prolonged (4 h) perfusion of the bile salt.

4. During bile salt perfusion, basal bicarbonate secretion remained unchanged but caerulein/secretin-stimulated bicarbonate secretion was slightly increased.

5. Plasma levels of pancreatic polypeptide, gastric inhibitory peptide and gastrin did not change significantly during duodenal perfusion with bile salt, but plasma levels of motilin were suppressed.

6. These results support the view that bile salts in the duodenum-5-regulate biliary and pancreatic secretion in man and affect plasma levels of motilin.
A Simple Method for Measuring Thickness of the Mucus Gel Layer Adherent to Rat, Frog and Human Gastric Mucosa: Influence of Feeding, Prostaglandin, N-Acetylcysteine and other Agents
Authors: Kerss Susan , Allen A. , Garner A.
Published: August 2015

1. A technique has been developed for measuring thickness of the gastric surface mucus gel layer. Mucosal sections (1·6 mm) were cut from frog and rat stomach and human antrum, mounted transversely and viewed by an inverse microscope (× 200 magnification) under dark field illumination or phase contrast. The mucus layer was readily distinguishable and its dimensions could be recorded by means of an eyepiece graticule.

2. Mean mucus gel thickness in rat, frog (Rana temporaria and Rana pipiens) and human was 73, 76, 55 and 192 μm respectively. However, there was variation in the average thickness of the gel layer between individual mucosae from the same species (up to twofold). Mucus thickness between adjacent regions of the same mucosal section also varied markedly (up to tenfold).

3. Topical administration of 16,16-dimethylprostaglandin E2 by oral intubation caused a significant increase in thickness in both rat and frog at doses of 5 μg/ml and 0·5 μg/ml respectively. Feeding and exposure of the mucosa to N-acetylcysteine (10–20%, w/v) produced variable effects, whereas pepsin (1 mg/ml) caused a marked reduction in thickness of the surface gel layer in both rat and frog.

4. The technique provides a rapid and simple method for determining gastrointestinal mucus thickness in relation to mucosal morphology. It is ideally suited for studying the control of mucus secretion and effect of drugs.
Exchangeable Sodium in Rats with Goldblatt Two-Kidney One-Clip Hypertension
Authors: McAreavey D. , Brown W. B. , Robertson J. I. S.
Published: August 2015

1. Exchangeable sodium (NaE) was measured serially in rats given a sodium-free diet to eat with sodium chloride solution (85 mmol/l) containing 22Na to drink.

2. After 15 days, nine rats had a left renal artery clip applied; nine had a sham operation.

3. There was no significant difference in NaE between the two groups during the 6 week period after clipping, at the end of which blood pressure was 189 ± 8 mmHg (mean ± sem) in the clipped group and 150 ± 2 mmHg in the sham-operated group (P < 0·001).

4. When the clips were removed blood pressure in the hypertensive group fell to 144 ± 4 mmHg.

5. On the first day after removal of the clip NaE was significantly lower in the clipped group than in the sham-operated group, but there were no significant differences thereafter.

6. Total body sodium (TBNa), measured at death, was consistently higher than NaE by a mean of 1·25 ± 0·08 mmol, in hypertensive and control rats alike.

7. We conclude that changes in sodium balance are not a necessary accompaniment of the development of hypertension in this two-kidney one-clip rat model.
Defective Reflex Control of Heart Rate in Dialysis Patients: Evidence for an Afferent Autonomic Lesion
Authors: Zoccali C. , Ciccarelli M. , Maggiore Q.
Published: August 2015

1. To localize the site of autonomic abnormality in patients undergoing haemodialysis, tests of overall autonomic function based on either changes in blood pressure (posture, sustained handgrip) or heart rate (Valsalva manoeuvre, 30:15 ratio, deep breathing test) were used. Integrity of the sympathetic efferent arc was examined by using the cold pressor test and the parasympathetic efferent arc by the atropine test. Eighteen patients and 12 control subjects were studied.

2. Changes in blood pressure on standing, sustained handgrip and in the cold pressor test were the same in the two groups.

3. In contrast, 11 patients had abnormal results in at least two of the three heart-rate-based tests.

4. Three of the 11 dialysis patients with evidence of autonomic involvement showed abnormal responses to atropine, indicating an efferent parasympathetic lesion, whereas the majority had a normal response to the atropine test, suggesting an afferent lesion only.

5. Evidence of autonomic involvement was not associated with hypertension nor confined to patients with dialysis hypotension.
Abolition, by Dopamine Blockade, of the Natriuretic Response Produced by Lower-Body Positive Pressure
Authors: Bennett E. D. , Tighe D. , Wegg W.
Published: August 2015

1. In a preliminary study, a positive pressure of 25 mmHg applied to the lower body raised right atrial pressure by a mean of 7 mmHg.

2. Sustained application of lower-body positive pressure (LBPP) in six normal adult males increased sodium excretion ([Na]V) from a control level of 126·5 ± 10 μmol/min to 213 ± 21 μmol/min (P = 0·003) and fractional sodium excretion (EfNa) from 0·7 ± 0·1 to 1·2 ± 0·1 (P = 0·001).

3. Urine flow (UF) increased from 0·85 ± 0·07 ml/min to 4·1 ± 0·8 ml/min (P = 0·002), osmolar clearance (Cosm) from 2·6 ± 0·13 ml/min to 4·2 ± 0·4 ml/min (P = 0·003) and free water clearance (CH2O)from −1·75 ± 0·1 ml/min to −0·1 ± 0·01 ml/min (P = 0·001). Creatinine clearance (Ccr) showed no significant change.

4. After dopamine blockade with domperidone, LBPP did not cause a rise in [Na]V or EfNa. However, urine flow, Cosm and CH2O remained significantly above control values, implying persistent suppression of antidiuretic hormone.

5. Dopamine blockade without positive pressure did not affect basal sodium excretion.
Decreased Phosphorylation of Polyphosphoinositides in the Erythrocyte Membrane of Spontaneously Hypertensive Rats
Authors: Marche P. , Koutouzov S. , Meyer P.
Published: August 2015

1. The distribution and metabolism of inositol phospholipids were studied in the erythrocyte membrane of spontaneously hypertensive and normotensive Wistar-Kyoto rats. The incorporation of 32P into these lipids was considered as an index of their turnover, and a reflection of their metabolism.

2. With [γ-32P]ATP as the source of label only the polyphosphoinositides (diphosphoinositide and triphosphoinositide) incorporated 32P. The levels of labelling were lower in hypertensive than in normotensive rats. Our data indicate that, in the hypertensive rats, the kinases responsible for the labelling of polyphosphoinositides exhibited decreased Vmax. for ATP.

3. These changes may be related to those described for calcium binding and transport in the erythrocyte of spontaneously hypertensive rats.
Proteinuria in Patients with Cirrhosis: Relationship between Renal and Hepatic Function
Authors: Milani L. , Gatta A. , Merkel C. , Ruol A.
Published: August 2015

1. In 37 patients with cirrhosis of the liver of different severity (11 in class A, 18 in class B, and 8 in class C, according to Child's criteria modified by Hobbs), inulin and p-aminohippurate clearances, total fractional protein excretion and the fractional clearances of α1-acid glycoprotein, albumin, transferrin, α2-macroglobulin and β2-microglobulin (in 20 patients) were determined.

2. Inulin clearance was lower than 70 ml/min in 19 patients and p-aminohippurate clearance was lower than 300 ml/min in 20 patients. Total fractional protein excretion was above normal in 19 patients; α1-acid glycoprotein fractional clearance was above normal in 11, albumin fractional clearance in 10, transferrin fractional clearance in five, α2-macroglobulin fractional clearance in three, and β2-microglobulin fractional clearance in 10.

3. The increases in protein excretion were independent of any impairment of renal tubular function. An inverse relationship between protein excretion and the clearances of inulin and p-aminohippurate was found. No difference in protein excretion was found between the three groups of patients with different degrees of liver damage.

4. The results suggest that in cirrhosis an increase in glomerular permeability is frequent, though generally slight; it is correlated with an impairment of kidney function and is independent of the severity of the liver damage.
Assessment of Glucose Turnover in Normal Man with the Use of a Non-Radioactive Isotopically Labelled Preparation, [6,6-2H]Glucose, as Tracer
Authors: Haigh J. W. , Johnston D. G. , McCulloch A. J. , Laker M. F. , Welby J. , Evans S.
Published: August 2015

1. Glucose kinetics were assessed in seven normal adult male subjects by an intravenous bolus technique with the use of a non-radioactive isotopically labelled preparation, [6,6-2H]glucose, as tracer. Tracer enrichment in plasma was assessed by gas chromatography-mass spectrometry. For comparison five subjects also received a simultaneous intravenous bolus of [6-3H]glucose and kinetics were assessed by conventional means.

2. Administration of [6,6-2H]glucose did not alter circulating glucose or insulin concentrations.

3. Glucose turnover, assessed by the use of [6,6-2H]glucose, was 11·4 (±0·9) μmol min−1 kg−1 and 11·6 (±0·5) μmol min−1 kg−1 with [6-3H]glucose. The mean metabolic clearance rate of glucose was 2·3 (±0·3) ml min−1 kg−1 with both isotopically labelled tracers. Estimates of mean residence time, glucose pool and glucose space were also similar by each technique.

4. [6,6-2H]Glucose is therefore an effective tracer and allows investigation of glucose kinetics without administration of a radioactive label.
The Effect of Regular Inhaled Salbutamol on the Airway Responsiveness of Normal Subjects
Authors: Higgs C. M. B. , Richardson R. B. , Laszlo G.
Published: August 2015

1. Airway responses to inhaled salbutamol were measured in two groups of six normal non-atopic subjects. In each group there was a dose-dependent increase in specific airways conductance after salbutamol inhaled in cumulative doses from 25 to 600 μg.

2. In the first group these studies were repeated weekly during and after the subjects had taken regular inhaled salbutamol for 4 weeks, in doses increasing to 500 μg four times daily by week 4. Then, while subjects were continuing to receive regular salbutamol, the studies were repeated after 48 h of inhaled sodium cromoglycate (20 mg four times daily) and again after 48 h of beclomethasone dipropionate (200 μg four times daily).

3. In the second group the studies were repeated after 10 days of regular inhaled salbutamol (500 μg four times daily).

4. There was no change in airway response to inhaled salbutamol after 4 weeks or 10 days regular salbutamol therapy, or after 48 h of sodium cromoglycate or beclomethasone dipropionate therapy.

5. This study did not show the development of resistance to β-agonists in the airways of normal subjects. These findings are discussed in the context of other studies which have shown the development of resistance, and we suggest that there may be a spectrum of susceptibility to the development of impaired airway responsiveness following regular treatment with β-adrenergic drugs.
Sodium—Potassium Pump Activity in Mineralocorticoid- and Glucocorticoid-Induced Hypertension
Authors: Wambach G. , Helber A. , Kaufmann W.
Published: August 2015

1. The activity of ouabain-sensitive Na+,K+-dependent ATPase and ouabain-sensitive ATPase was measured in the microsomal fractions of kidney, liver and heart tissue of Sprague-Dawley rats treated with DOCA (10 mg day−1 kg−1 for 6 days, systolic blood pressure 143 ± 13 mmHg, n = 9) or 6 α-methylprednisolone (100 mg day−1 kg−1 for 6 days, systolic blood pressure 140 ± 19 mmHg, n = 9) and of a control group (systolic blood pressure 124 ± 12 mmHg, n = 9).

2. In the kidney, the ouabain-sensitive Na+,K+-ATPase activity (μmol of phosphate h−1 mg−1 of protein) was increased in the DOCA-treated (33.0 ± 6.9) and in the prednisolone-treated groups (30.8 ± 6.9) compared with that in the control group (26.4 ± 3.4) (P < 0.05). In the liver, the ouabain-sensitive Na+,K+-ATPase activity was elevated in the prednisolone-treated animals only (4.8 ± 1.3 vs 3.1 ± 0.8 in the controls, P < 0.025). The ouabain-sensitive Na+,K+-ATPase activity in heart tissue was similar in all three groups. The ouabain-insensitive ATPase activity was not altered by DOCA or prednisolone in the tissues studied.

3. In a separate study, the activity of the ouabain-sensitive Na+,K+-ATPase in erythrocyte ghosts was found to be elevated in 10 patients with Cushing's syndrome (0.91 ± 0.35 μmol of phosphate h−1 mg−1 of protein) compared with five patients with primary aldosteronism and compared with 12 normotensive control subjects (0.38 ± 0.08) (P < 0.005).

4. These data demonstrate an increased Na-K pump activity in the kidney in mineralocorticoid-induced hypertension. Glucocorticoids in addition activate the Na-K pump in a variety of other tissues. This could partially explain the redistribution of volume from the intracellular to the extracellular space.
A Reappraisal of the Diagnostic Criteria for Primary Aldosteronism
Authors: Bravo E. L. , Tarazi R. C. , Fouad F. M. , Textor S. C.
Published: August 2015

1. Results in 80 patients with primary aldosteronism (70 with tumour, 10 with hyperplasia) who underwent stimulation and suppression tests were analysed to assess the usefulness of several screening techniques.

2. On normal dietary sodium, normokalaemia was found in 27.5% of patients; 12.5% remained so despite 3 days of salt loading. Suppressed plasma renin activity (PRA: less than 1.43 pmol/l after stimulated conditions) gave a false-negative rate of 36%. Thus sole reliance on either hypokalaemia (serum potassium less than 3.5 mmol/l) or suppressed PRA as primary screening tests would have overlooked about a third of the patients in this series.

3. The single best diagnostic test for primary aldosteronism was the measurement of aldosterone excretion rate after 3 days of salt loading.

4. An anomalous postural fall in plasma aldosterone concentration when present, coupled with adrenal venous sampling, provided the best indicators of the presence of an aldosterone-producing adenoma.