bluuebunny/crossref_metadata_2025 huggingface dataset:
α-Adrenoceptors and Age-Dependent Decrease of Plasma Renin Activity in Essential Hypertension
Authors: Salvetti A. , Pedrinelli R. , Arzilli F. , Sassano P. , Leonetti G. , Terzoli L. , Bianchini C. , Fruscio M.
Published: August 2015

1. A stepwise infusion of phentolamine was administered to 26 patients with mild uncomplicated essential hypertension, whose basal renin was inversely related to age.

2. Phentolamine caused a dose-related increase of plasma renin activity, which was independent of mean blood pressure and heart rate changes.

3. The maximum increment of plasma renin activity was inversely related to age and the dose-response curve of plasma renin activity was steeper in the younger group than in older patients.

4. Our data do not support the hypothesis than an increased α-adrenergic tone in elderly people may explain the age-dependent decline of renin in uncomplicated essential hypertension.
Effects of Combined α- and β-Receptor Blockade on Peripheral Circulation in Essential Hypertension
Authors: Heck I. , Trübestein G. , Stumpe K. O.
Published: August 2015

1. Six weeks' treatment with labetalol (600 mg/day) significantly reduced systolic and diastolic blood pressures in 24 patients with essential hypertension. There was a small but not significant decrease in heart rate.

2. After 6 weeks of therapy mean digital arterial blood flow at rest and during reactive hyperaemia had increased by 26%.

3. In nine essential hypertensive patients intravenous administration of 100 mg of labetalol caused prompt and striking reductions of systolic and diastolic blood pressures without significant changes in heart rate. There was a consistent and significant increase in peripheral blood flow by 32% 5 min after administration of the drug.

4. Antagonism of α-receptors in addition to β-receptors might improve peripheral arterial blood flow while achieving antihypertensive control. Thus labetalol, owing to its favourable haemodynamic effects, may have advantages over conventional pure β-receptor-blocking agents.
Comparison of Nasal and Bronchial Mucociliary Clearance in Young Non-Smokers
Authors: Puchelle Edith , Aug F. , Zahm J. M. , Bertrand A.
Published: August 2015

1. Nasal and bronchial mucociliary clearance have been studied in ten non-smokers (aged 19–23 years). Nasal mucociliary transport was evaluated by measuring the transport rate of a single radioactive (99mTc) particle deposited on the nasal mucosa. Bronchial clearance was measured after inhalation of insoluble radioactive anionic particles (diameter 7.4 ± 1.5 μm). The initial deposition of the aerosol and subsequent clearance over 1 h was monitored with a γ-camera

2. The initial particle deposition was concentrated centrally and was similar in all subjects. The percentage of the total deposition located in the central zone was 78.2 ± 5.8. The range for nasal transport rate (0–12.6 mm/min) and bronchial mucociliary clearance (18.1–77.0%) was large

3. An inverse relationship (rs = −0.63, P < 0.05) was observed between nasal transport rate and bronchial clearance, suggesting that, in young non-smokers, the lower the rate of the nasal mucociliary transport the faster the bronchial mucociliary clearance.
Effect of Fasting on the Disappearance of Injected Alanine and 3-Hydroxybutyrate in Obese Subjects
Authors: Swaminathan R. , Morgan D. B. , Wales J. K.
Published: August 2015

1. The blood concentrations of 3-hydroxybutyrate and alanine were measured before and after they were separately injected into obese patients who were taking a 1.68 MJ (400 kcal) diet and again when they had starved for 4 days and 28 days.

2. The disappearance of the injected metabolite was exponential and its half-life and volume of distribution were calculated.

3. The concentration of ketones (both 3-hydroxybutyrate and acetoacetate) was raised in the patients when they were taking the low-calorie diet and increased a further sevenfold during starvation. This further increase was associated with an increase in the half-life of injected 3-hydroxybutyrate.

4. The pre-injection concentration of alanine almost halved during starvation and the half-life of injected alanine increased.

5. If the changes in half-life of exogenous 3-hydroxybutyrate and alanine apply to endogenous metabolites, then these results suggest that the increase in blood ketone concentration during starvation is at least partly due to a decreased clearance of ketones and the decrease in blood alanine concentration is associated with a marked decrease in production rate of alanine.
The Relation between Membrane Cholesterol and Phospholipid and Sodium Efflux in Erythrocytes from Healthy Subjects and Patients with Chronic Cholestasis
Authors: Jackson P. A. , Morgan D. B.
Published: August 2015

1. The cholesterol and phospholipid content of the cell membrane and the efflux of sodium were measured in the erythrocytes of patients with chronic cholestasis and in healthy subjects.

2. The membranes from the patients contained more cholesterol and phospholipid and had a higher cholesterol/phospholipid molar ratio than the membranes from the healthy subjects.

3. The sodium efflux rate constant was reduced in the patients and this was entirely due to a reduction in the frusemide-sensitive efflux rate constant. There was no difference in either the ouabain-sensitive or the ouabain plus frusemide-resistant rate constants.

4. This reduction in the frusemide-sensitive rate constant was associated with a reduction in the erythrocyte sodium content.

5. When erythrocytes were loaded with cholesterol in vitro the frusemide-sensitive efflux rate constant was reduced by an amount similar to that observed in the patients. In addition, however, there was a reduction in the ouabain-sensitive efflux rate constant and an increase in the erythrocyte sodium content; neither of these changes was observed in the patients in vivo.
Zinc Deficiency and Photoreceptor Dysfunction in Chronic Liver Disease
Authors: Keeling P. W. N. , O'Day J. , Ruse W. , Thompson R. P. H.
Published: August 2015

1. In nine patients with chronic liver disease photoreceptor function was tested, by measurement of the B-wave amplitude of dark adaptation by electroretinography, and the leucocyte content and plasma concentration of zinc were determined.

2. Four of the patients were leucocyte zinc-depleted and had impaired photoreceptor function, but this was normal in the five with normal leucocyte zinc content.
Comparative Effect of Diuretics on Renal Water Excretion in Hyponatraemic Oedematous Disorders
Authors: Szatalowicz V. L. , Miller P. D. , Lacher J. W. , Gordon J. A. , Schrier R. W.
Published: August 2015

1. The effects of intravenous chlorthiazide and frusemide on urinary osmolality were compared in 19 hyponatraemic oedamatous patients.

2. Frusemide (1 mg/kg) caused production of a dilute urine (urine/plasma osmolality ratio, Uosm./Posm., 1.64–0.84, P < 0.01) whereas chlorthiazide (10 mg/kg) did not (Uosm./Posm. 1.54–1.34, not significant).

3. The osmolar clearance (Cosm.) was higher after frusemide than after chlorthiazide (11.45 vs 4.99 ml/min, P < 0.01). When the doses of frusemide (0.25–0.5 mg/kg) and chlorthiazide (20 mg/kg) were chosen to give a similar Cosm. (7.25 vs 7.48 ml/min, not significant), the Uosm./Posm. was still lower after frusemide (2.20–1.00, P < 0.001) than after chlorthiazide (1.75–1.26, P < 0.01).

4. Exogenous vasopressin did not increase the low Uosm./Posm. after frusemide (1.00–1.00, not significant) but increased the ratio after chlorthiazide (1.34–1.68, P < 0.001).

5. These results indicate that frusemide, but not chlorthiazide, leads to the excretion of a dilute urine in hyponatraemic oedematous patients. This dilution is not due to a greater solution excretion but is associated with a resistance to the action of vasopressin.
Effect of Locally Applied Subatmospheric Pressure on Subcutaneous Blood Flow during the Course of Acute Myocardial Infarction
Authors: Skagen K.
Published: August 2015

1. The effect of locally applied subatmospheric pressure on subcutaneous blood flow was studied in six patients with acute myocardial infarction.

2. Blood flow was measured by the local 133Xe washout technique.

3. Application of subatmospheric pressures of −80 and −150 mmHg to the labelled area induced no vasoconstriction on day 1. On day 7 pressures of −40, −80 and −150 mmHg induced a decrease in blood flow of about 40–50%.

4. The absence of a vasoconstrictor response to locally applied subatmospheric pressure on day 1 could not be due to decreased venous distensibility. The underlying mechanism may be neuronal inhibition, probably antidromic, in sympathetic fibres.
Bone Mineral Content of the Lumbar Spine in Normal and Osteoporotic Women: Cross-Sectional and Longitudinal Studies
Authors: Krølner B. , Nielsen S. Pors
Published: August 2015

1. Bone mineral content of the second, third and fourth lumbar vertebrae was determined in normal women and women with clinical osteoporosis by using dual-photon (153Gd) absorptiometry.

2. A cross-sectional study of 70 normal women (aged 19–88 years) showed a bone loss of 44% from the age of around 34 years throughout life.

3. Longitudinal data from 59 normal women confirmed that the vertebral bone loss started before the menopause. An accelerated bone loss amounting to nearly 6% per year was seen immediately after the menopause. The bone loss of older women was slower.

4. Mean lumbar bone mineral content of 36 women (aged 48–93 years) with recent fractures of their femoral neck after minor trauma equalled that of age-matched normal women. Lumbar bone mineral content of the women with intratrochanteric femoral neck fractures was lower than that of the women with medial femoral neck fractures.

5. Mean lumbar bone mineral content of 72 women (aged 58–89 years) with primary osteoporosis was 41% lower than that of normal premenopausal women and 18% lower than that of age-matched controls. A weak inverse relationship between lumbar bone mineral content and the number of compression fractures was found. A weak inverse relationship between lumbar bone mineral content and the number of compression fractures was found.

6. Women with lumbar bone mineral content values below the 95% confidence limits for normal premenopausal women are at risk of future vertebral compression fractures, the fracture risk being inversely related to lumbar bone mineral content.
Circadian Variation in Adrenergic Responses in Asthmatic Subjects
Authors: Barnes P. J. , Fitzgerald G. A. , Dollery C. T.
Published: August 2015

1. To determine whether circadian variations in adrenergic responsiveness might underlie nocturnal wheezing in asthma, we measured cardiovascular, airway and plasma adenosine 3′:5′-cyclic monophosphate (cyclic AMP) responses to stepwise infusions of l-adrenaline (0.01, 0.03 and 0.075 μg min−1 kg−1) at 4 h intervals over 24 h in five extrinsic asthmatic men.

2. Peak expiratory flow, blood pressure, heart rate and plasma cyclic AMP showed a significant circadian variation with peak values at 16.00 hours and trough values at 04.00 hours.

3. The β2-adrenoceptor-mediated increases in peak flow and cyclic AMP were similar at all times, but adrenergic responsiveness (measured by response/log dose of infused adrenaline) was greater at 04.00 hours than at 16.00 hours because of the lower baseline values at night.

4. Blood pressure and heart rate responses to adrenaline infusions did not significantly differ over 24 h.

5. Airway responses to inhaled adrenaline were studied on the second day; the mean peak flow after adrenaline was similar at 16.00 hours to that at 04.00 hours and since the pretreatment values were lower at 04.00 hours, the magnitude of response to inhaled adrenaline was greater at night.

6. We conclude that there is no significant circadian change in adrenergic responses in asthma and that adrenoreceptor dysfunction is not important in the pathogenesis of nocturnal asthma.
Increase of Whole-Body Calcium and Skeletal Mass in Normal and Osteoporotic Adult Rats Treated with Parathyroid Hormone
Authors: Hefti E. , Trechsel U. , Bonjour J.-P. , Fleisch H. , Schenk R.
Published: August 2015

1. The effect of long-term administration of parathyroid hormone (PTH) on whole-body calcium and ash weight of individual bones has been studied in normal and osteoporotic adult female rats in order to examine whether such a treatment could induce a positive calcium balance.

2. Osteoporosis was induced by calcium restriction during pregnancy and lactation. Sequential measurements of whole-body calcium were made by neutron activation.

3. In non-osteoporotic intact and thyroparathyroidectomized rats a daily dose of 75 units of human PTH 1–34 given subcutaneously for 3 weeks increased whole-body calcium.

4. In osteoporotic animals 25–50 units of either bovine PTH 1–84 or human PTH 1–34 given subcutaneously twice daily for 6 weeks increased both whole-body calcium and ash weight of individual bones. Microradiographic examination of the tibiae indicates, however, that PTH administration does not result in the restoration of individual trabeculae lost during the development of osteoporosis.

5. The results show that PTH can enhance skeletal mass in both normal and osteoporotic rats. In osteoporotic animals the restoration of whole-body calcium and ash weight of individual bones is not accompanied by a return of the morphological structure of the tibia to normal.
The Effect of Renal Function on Changes in Circulating Concentrations of 1,25-Dihydroxycholecalciferol after An Oral Dose
Authors: Papapoulos S. E. , Clemens T. L. , Sandler L. M. , Fraher L. J. , Winer J. , O'riordan J. L. H.
Published: August 2015

1. 1,25-Dihydroxycholecalciferol [1,25-(OH)2-D3] was administered orally to four normal subjects and six patients with chronic renal failure not on dialysis. The serum concentration of 1,25-(OH)2D3 was measured by radioimmunoassay in both groups from samples taken before, and at regular intervals up to 48 h after, the oral dose.

2. The plasma half-time for the disappearance of the administered 1,25-(OH)2D3 was estimated by determining the time for a 50% reduction from the peak increment of the sterol. In normal subjects the calculated value ranged from 5 to 8 h compared with 18 to 44 h in uraemic patients.

3. It appears from our studies that in uraemic subjects there is impaired ability to metabolize or excrete 1,25-(OH)2D3.
The Effect of Intrarenal Infusion of Bile on Kidney Function in the Dog
Authors: Alon U. , Berant M. , Mordechovitz D. , Better O. S.
Published: August 2015

1. Obstructive jaundice sensitizes the kidney to anoxic damage. To clarify further this phenomenon the effect of unilateral infusion of bile on kidney function was studied. The contralateral intact kidney served as control.

2. Intrarenal infusion of diluted bile (1:10) resulted in an ipsilateral fourfold increase in mean rate of urinary flow (P < 0.01), threefold increase in mean fractional excretion of sodium (P < 0.05) and more than 50% increase in mean rates of potassium excretion (P < 0.05). Urinary flow rate and electrolyte excretion returned to baseline upon cessation of bile infusion. The mean clearances of inulin and p-aminohippurate were unchanged during intrarenal bile infusion.

3. Intrarenal infusion of isotonic taurocholate solution (20 mmol/l) mimicked the diuretic, natriuretic and kaliuretic effects of diluted bile, whereas intrarenal infusion of bilirubin did not cause any change in the excretion of electrolytes.

4. It is concluded that increase in circulating bile acids rather than hyperbilirubinaemia may alter kidney function during obstructive jaundice. Acute cholaemia may cause volume depletion by increasing urinary salt loss. This in turn may aggravate the direct nephrotoxicity of circulating bile compounds.
Effect of Atropine on Alveolar Gas Mixing in Man
Authors: Kox W. , Langley F. , Horsfield K. , Cumming G.
Published: August 2015

1. Atropine is known to diminish broncho-motor tone. In order to investigate the acute effect of atropine on respiration and alveolar gas mixing, a dose of 2.4 mg was given intravenously.

2. Ten normal male volunteers were each studied three times with a nitrogen washout method, once before administration of atropine and then 20 min and 60 min thereafter.

3. After the administration of atropine there was a reduction in tidal volume, a slight increase in frequency of respiration and an increase in series dead space. The tidal mixing volume showed a fall of 25%. In spite of the reduced alveolar dead space the effective mixing volume fell by 29%. Multi-breath alveolar mixing efficiency fell by 3.5%.

4. Multi-breath alveolar mixing efficiency was found to be less with smaller tidal mixing volumes, a fall of 518 ml in the latter causing a reduction of 17.2% in mixing efficiency.

5. A reduction of 100 ml in tidal volume in normal subjects was associated with a decrease of 6.9% in alveolar mixing efficiency. In the subjects receiving atropine tidal volume reduced by 96 ml, but the observed fall in alveolar mixing efficiency was only 3.5%, This suggests an improvement in alveolar mixing of 3.4% due to the administration of atropine. Despite this small improvement, the mixing efficiency is still only 66%. The residual inefficiency of 34% cannot therefore be explained on the basis of broncho-motor tone.
Non-Pancreatic Hydrolysis of N-Benzoyl-l-Tyrosyl-p-Aminobenzoic Acid (PABA-peptide) in the Human Small Intestine
Authors: Sterchi E. E. , Green J. R. , Lentze M. J.
Published: August 2015

1. Hydrolysis of N-benzoyl-l-tyrosyl-p-aminobenzoic acid (PABA-peptide) has been measured in soluble and particulate fractions of human small intestinal mucosa.

2. Both soluble and particulate fractions contained enzymic activity capable of splitting the PABA-peptide. In the paniculate fractions this activity increased threefold towards the distal small intestine.

3. Neither soluble nor paniculate activity was inhibited by the chymotrypsin inhibitor 1-chloro-4-phenyl-3-l-toluene-p-sulphonamidobutan-2-one (TPCK).

4. Column chromatography on Sephacryl S-300 resolved a peak of PABA-peptide hydrolase activity that was clearly distinct from other known brush-border peptide hydrolases and from added chymotrypsin standard.

5. This PABA-peptide hydrolase thus represents a distinct intestinal enzyme, possibly bound to the brush-border membrane, which could account for the residual urinary PABA recovery observed in patients and animal models with exocrine pancreatic insufficiency.
Abnormalities of Bile Acids in Serum and Bile from Patients with Myotonic Muscular Dystrophy
Authors: Tanaka Kaoru , Takeshita Kenzo , Takita Minoru
Published: August 2015

1. Serum bile acids in seven patients with adult type myotonic dystrophy and 22 normal persons were quantitatively analysed by gas—liquid chromatography and gas chromatography—mass spectrometry for cholesterol, γ-glutamyltransferase and bilirubin. There was no bile obstruction in any patient.

2. Deoxycholic acid values in all mothers of patients with congenital type myotonic dystrophy were three times (2.1 μmol/l) that of the control (0.7 μmol/l).

3. Uncommon bile acids were detected in the patients' sera. One of them appeared to be dihydroxymono-oxocholanic acid, having a longer side chain. Another one appeared to be dihydroxycholanic acid, with a steroid-nucleus structure similar to chenodeoxycholic acid and with a longer side chain.

4. Biliary bile acids from three patients and one normal person were also analysed, and this revealed a remarkable decrease in ursodeoxycholic acid in the patients.

5. The presence of bile acid abnormality in patients with myotonic muscular dystrophy is proposed.
Myofibrillar Protein Catabolic Rates in Cirrhotic Patients with and without Muscle Wasting
Authors: Zoli M. , Marchesini G. , Dondi Cristina , Bianchi G. P. , Pisi E.
Published: August 2015

1. The urinary excretion of 3-methylhistidine and creatinine was measured in 15 controls and in two groups of 15 patients with liver cirrhosis, with and without severe muscle wasting. All subjects were on a meat-free diet. The values obtained were used to calculate the fractional catabolic rate of myofibrillar protein.

2. In patients without muscle wasting 3-methylhistidine excretion was high in the presence of normal urinary creatinine. The fractional breakdown rate was significantly increased as compared with that of controls.

3. In patients with severe muscle wasting 3-methylhistidine excretion was normal and urinary creatinine was remarkably reduced. The myofibrillar catabolic rate was further increased compared with that of controls and of the other group of patients.

4. 3-Methylhistidine and creatinine excretion allow a complete evaluation of myofibrillar protein degradation, which appears to be remarkably increased in cirrhotic patients. The relevance of increased myofibrillar protein turnover in muscle wasting of subjects with advanced cirrhosis remains to be determined.
Detection Latency of Added Loads to Breathing
Authors: Burdon J. G. W. , Killian K. J. , Campbell E. J. M.
Published: August 2015

1. Detection latency of a range of added elastic (0·95–4·50 kPa/l) and resistive (0·73–3·29 kPa l−1 s) loads to breathing were measured in five normal subjects. Detection latency was defined as the time from the onset of the breath to detection of the load.

2. Detection latency followed a curvilinear relationship when plotted as a function of the magnitude of the added loads. A similar relationship was found with both elastic and resistive loads although detection latencies to added elastances were longer than for added resistances.

3. When the added load was expressed in terms of comparable magnitude (peak inspiratory pressure) detection latencies for added elastances were found to be consistently longer than for added resistive loads.

4. These studies show that the detection latency to added inspiratory loads follows a reciprocal relationship, that detection latencies for elastic and resistive loads are clearly different and suggest that these loads are detected during the respiratory cycle at a time when the mechanical information regarding muscular pressure is greatest.
Renal Clearance of [14C]oxalate: Comparison of Constant-Infusion with Single-Injection Techniques
Authors: Prenen J. A. C. , Boer P. , Mees E. J. Dorhout , Endeman H. J. , Spoor S. M. , Oei H. Y.
Published: August 2015

1. The renal clearance of [14C]oxalate was assessed by the constant-infusion technique and single-injection technique (plasma sampling only: one-compartment and two-compartment model; plasma and urine sampling). Healthy volunteers and patients with renal stones were studied.

2. Results with the constant-infusion techniques (with and without urine sampling) were not significantly different from each other.

3. The renal clearance of [14C]oxalate measured with the single-injection technique as compared with the constant-infusion technique was overestimated in the single-injection one-compartment model (52%) as well as in the two-compartment model (30%).

4. The calculated level of plasma oxalate in the healthy volunteers ranged from 1·04 to 1·78 μmol/l (mean 1·39).

5. The biological half-life of [14C]oxalate, estimated by the cumulative excretion of 14C in urine after equilibrium had been established, was 128 min (range: 113–142).

6. The oxalate/creatinine clearance ratio in the healthy volunteers ranged from 1·73 to 2·22 (mean 2·01).
Effect of Isolated Cholaemia on Systemic Haemodynamics and Kidney Function in Conscious Dogs
Authors: Alon U. , Berant M. , Mordechovitz D. , Hashmonai M. , Better O. S.
Published: August 2015

1. Systemic haemodynamics and kidney function were studied in the same dogs before and 14 days after choledochocaval anastomosis.

2. All dogs became deeply jaundiced whereas parenchymal liver function remained unchanged as assessed biochemically.

3. After choledochocaval anastomosis there was a decrease in mean arterial pressure (118 ± 18 to 98 ± 13 mmHg, P < 0·005), and total peripheral resistance (4073·8 ± 620·0 to 3327·6 ± 244·9 kPa l−1 s kg, P < 0·01), whereas mean cardiac index and plasma volume corrected for body weight did not change.

4. Despite their disturbed systemic haemodynamics the cholaemic dogs had normal mean glomerular filtration rate and renal plasma flow. Maximal ability to concentrate and dilute the urine was, however, impaired during cholaemia.

5. It is concluded that cholaemia per se cuases peripheral vasodilatation, hypotension and renal tubular dysfunction. Similar phenomena in jaundiced patients may contribute to their susceptibility to postoperative shock and acute renal failure.
Blood Viscosity, Glycaemic Control and Retinopathy in Insulin-Dependent Diabetes
Authors: Poon P. Y. W. , Dornan T. L. , Orde-Peckar C. , Mullins R. , Bron A. J. , Turner R. C.
Published: August 2015

1. In a cross-sectional study, 32 insulin-treated diabetic patients had elevated low shear (27·1 vs 22·1 mPa s, P < 0·05) and high shear blood viscosity (5·4 vs 5·0 mPa s, P < 0·05) when compared with 10 non-diabetic controls. After correction to 45% packed cell volume, the abnormality had a tendency to be greater in patients with proliferative (mean low shear viscosity, 30·8 mPa s) than background (29·2 mPa s) or nil/minimal retinopathy (27·6 mPa s, 0·05 < P < 0·07, permutational trend test).

2. The fibrinogen levels were higher in the diabetic group (P < 0·05) and correlated with the low shear blood viscosity (rs = 0·38, P < 0·05).

3. In a prospective study, 74 insulin-treated diabetic patients with background retinopathy were randomized into two groups. Thirty-six patients were on attempted improved therapy (A group); in these the mean glycosylated haemoglobin (Hb A1c) fell within 1 year (11·6 to 10·1%, P < 0·001). Both the corrected low shear blood and plasma viscosity fell similarly (P < 0·001). The fall was greater than in those patients who were kept on usual therapy (U group) and whose glycosylated haemoglobin did not change significantly (11·7 to 11·4%) over the year.

4. The effect of diabetes on blood viscosity may not be a direct pathological factor, as the same increased viscosity would be produced by a mean increase of 1·7% in packed cell volume, compared with a population range of 14% packed cell volume.
The Effect of Propranolol or Metoprolol on Thermoregulation during Insulin-Induced Hypoglycaemia in Man
Authors: Macdonald I. A. , Bennett T. , Gale E. A. M. , Green J. Hilary , Walford S.
Published: August 2015

1. The effects of metoprolol and propranolol on heat production and body temperature have been studied in six male subjects during insulin-induced hypoglycaemia in a thermoneutral environment. Hypoglycaemia was induced by insulin infusion on three occasions in each subject, accompanied by the infusion of sodium chloride solution (154 mmol/l) (control), metoprolol (β1-selective antagonist) or propranolol (non-selective antagonist).

2. During the period of hypoglycaemia in the control experiments mean heat production (calculated from respiratory gas exchange) increased by 1·07 ± sem 0·13 kJ/min and remained elevated for 30−40 min. This heat production response was reduced by metoprolol and abolished by propranolol. During the recovery period, heat production was significantly reduced in the presence of propranolol.

3. Skin and core temperatures fell during the period of hypoglycaemia in all three experiments. The fall in skin temperature was significantly greater in the presence of propranolol (−2·51 ± 0·47°C). The reductions in core temperature recorded during the three experiments were similar (control −0·73 ± 0·17, metoprolol −0·99 ± 0·21, propranolol −0·88 ± 0·22°C), but core temperature was still falling at the end of the propranolol experiment.

4. The cardiovascular responses to hypoglycaemia were similar in the control and metoprolol experiments but were substantially modified by propranolol. During the period of hypoglycaemia in the control experiments, plasma adrenaline levels rose to 7·78 ± 1·79 nmol/l; significantly higher levels were measured in the metoprolol (10·11 ± 1·64) and propranolol (22·76 ± 7·02) experiments. The very high adrenaline levels may have been responsible for the modified cardiovascular responses to hypoglycaemia observed in the propranolol experiment.
Impaired Pancreatic Polypeptide Release to Insulin Hypoglycaemia in Chronic Autonomic Failure with Postural Hypotension: Evidence for Parasympathetic Dysfunction
Authors: McGrath B. P. , Stern A. I. , Esler M. , Hansky J.
Published: August 2015

1. Release of pancreatic polypeptide (PP) is largely under vagal control and measurement of change in PP after insulin hypoglycaemia offers a non-invasive method of assessing vagal activity.

2. Changes in blood sugar and PP after intravenous insulin (0·2 unit/kg) were examined in six patients with idiopathic chronic autonomic failure (AF) and 12 control subjects. Six of the controls were studied before and after atropine treatment.

3. The PP levels in controls rose from 32 ± 9 (mean ± sem) to 236 ± 54 pmol/l after 45 min. Patients had similar baseline values (23 ± 5 pmol/l) but a markedly reduced and delayed PP response to hypoglycaemia (49 ± 19 pmol/l at 90 min). This impaired PP response was similar to that seen in controls after atropine.

4. The impaired PP response to insulin hypoglycaemia in patients with AF strongly suggests a dysfunction of vagal activity which is often clinically inapparent.
The Effects of Almitrine on the Ventilatory Response to Hypoxia and Hypercapnia in Normal Subjects
Authors: Stradling J. R. , Barnes P. , Pride N. B.
Published: August 2015

1. Almitrine at a dose of 0·5 mg h−1 kg−1 given intravenously over 2 h had no effect on resting ventilation in normal males.

2. There was a small, but insignificant, rise in the hypercapnic drive to breathe as compared with placebo.

3. A large rise in the hypoxic drive to breathe was seen in response to almitrine.

4. These findings support the claim that almitrine has its action on ventilation via the peripheral chemoreceptors.

5. No correlation between blood levels of almitrine and the rise in hypoxic response was seen.
Effects of Temperature and Humidity of Inhaled Air on the Concentration of Ethanol in a Man's Exhaled Breath
Authors: Jones A. W.
Published: August 2015

1. Ten healthy men each drank a moderate dose of ethanol in experiments to test if the temperature and moisture content of inhaled air could alter the concentration of ethanol in exhaled breath.

2. They breathed air at various temperatures and relative humidities (RH) for about 1 min before the concentration of ethanol and the temperature of end-expired breath were determined. Control breaths were analysed after the same men breathed ordinary room air (23°C, 55% RH). All tests were made during the postabsorptive phase of ethanol metabolism and the breath samples were analysed by gas-liquid chromatography.

3. When the men breathed cold dry air (5°C, 0% RH), the expired ethanol concentration decreased by 9·6 ± 0·69% (mean ± se) and breath temperature dropped by 1·40 ± 0·08°C. Cold moist air (5°C, 100% RH) decreased breath ethanol concentration by 6·4 ± 1·02% and breath temperature dropped by 1·1 ± 0·07°C. With hot dry air (80°C, 0% RH) as the breathing medium the concentration of ethanol was lowered by 4·3 ± 1·27% but expired breath temperatures were unchanged from the control tests. On breathing hot moist air (50°C, 100% RH), breath ethanol concentrations decreased by 10·3 ± 0·59%, even though breath temperatures rose by 1·8 ± 0·14°C above that of the controls.

4. Ethanol dissolves in the watery mucous membrane of the upper respiratory tract and can equilibrate with inhaled and exhaled air. It seems likely that during exchanges of heat and water vapour between respired air and the mucus, which largely depends on the temperature and humidity of inhaled air, the equilibrium of ethanol at the breath/mucus interface becomes disrupted. This leads to changes in the concentration of ethanol in expired air.
Liver Coenzyme a Ester Content: Comparison between Reye's Syndrome and Control Subjects
Authors: Kang Ellen S. , Capaci Mary T. , Korones David N. , Tekade Nilima
Published: August 2015

1. The concentrations of the acid soluble and insoluble coenzyme A (CoA) esters were measured in samples of liver obtained at autopsy from Reye's syndrome and control subjects because the long chain fatty CoA compounds which make up the bulk of the acid insoluble CoA esters are known to inhibit a number of mitochondrially located enzymes, several of which may be affected in Reye's syndrome.

2. Concentrations of the acid insoluble esters varied widely in both control and Reye's liver samples. The difference between the mean values was not statistically significant (1·06 ± sem 0·33 nmol/g wet weight in Reye's samples vs 0·88 ± 0·21 in control samples).

3. Concentrations of the acid soluble CoA esters, which include the short chain fatty CoA compounds, were higher in Reye's liver samples than in samples from controls. The mean value for Reye's samples was 104·8 ± sem 29·4 nmol/g of liver compared with 26·4 ± 10·1 nmol/g for control samples (P < 0·05).

4. Studies with rats designed to assess postmortem change indicate that the liver concentration of the acid insoluble CoA compounds does not change during a 4 h period at 4°C. This finding suggests that the observations made in Reye's liver was probably due to a premorbid abnormality.

5. These findings implicate a block in the β-oxidation of fatty acids and could account for the reported relative increase in the concentrations of the short to medium chain fatty acids in the plasma of Reye's syndrome patients.
Inhibition of Adrenaline-Forming Enzyme in the Brain Prevents One-Kidney, One-Clip Hypertension and Deoxycorticosterone Acetate-Salt Hypertension in the Rabbit
Authors: Rosendorff C. , Melamed J. R. , Hurwitz M. L. , Coull A. , Jarvis A.
Published: August 2015

1. Phenylethanolamine N-methyltransferase (PNMT) converts noradrenaline into adrenaline and brain PNMT is elevated in spontaneously hypertensive and deoxycorticosterone acetate (DOCA)-salt hypertensive rats. In view of the evidence for the involvement of central adrenergic neurons in renal hypertension, we measured the blood pressure response in one-clip, one-kidney Goldblatt hypertensive and DOCA-salt hypertensive rabbits to the PNMT inhibitor SK&F 64139, injected into the lateral cerebral ventricles.

2. Intracerebroventricular injection of SK&F 64139 (10 μg/kg) significantly attenuated the mean arterial blood pressure rise in one-clip, one-kidney and DOCA-salt rabbits, at 4 and 8 weeks.

3. These findings support the idea that hypertension in this animal model requires an intact adrenaline biosynthetic process, and that central catecholaminergic neurons may be involved in the pathogenesis of low-renin volume dependent forms of hypertension.
Erythrocyte Membrane and Renal Function in Relation to Hypertension in Rats of the Milan Hypertensive Strain
Authors: Ferrari P. , Cusi D. , Barber B. , Barlassina C. , Vezzoli G. , Duzzi L. , Minotti E. , Bianchi G.
Published: August 2015

1. The aim of this study was to compare certain renal and erythrocyte functions in the Milan hypertensive strain (MHS) of rats and in normotensive control animals (MNS).

2. Under experimental conditions close to those in conscious unmanipulated animals, the glomerular filtration rate (GFR) per g kidney weight was higher and the kidney weight/body weight ratio lower in MHS than in MNS rats (P < 0.001). This suggests that there is increased transtubular ion transport in MHS animals.

3. The MHS rats had a higher rate constant for outward Na+-K+ cotransport than the MNS animals (P < 0.02), their intra-erythrocyte sodium concentrations were lower (P < 0.05) and their erythrocyte volume was smaller (P < 0.001). Therefore, accelerated cell membrane sodium outward cotransport seems to reset the volume and the sodium content of the erythrocytes of MHS rats at a lower level.

4. We speculate that increased transport of ions across the cell membrane may be an abnormality common to erythrocytes and renal tubular cells in MHS rats.
Peripheral Vascular Changes after Treatment of Severe Hypertension
Authors: Gudbrandsson T. , Hansson L. , Herlitz H. , Sivertsson R.
Published: August 2015

1. Blood flow resistance was studied in two peripheral vascular beds in 15 patients with previous malignant hypertension and in a matched group of patients with treated ‘benign’ hypertension and in matched control subjects. Studies were made during rest and after the induction of maximal vasodilatation.

2. In the hand (representing mainly a skin vessel bed), both hypertensive groups had significantly higher resistance at maximal dilatation than the normotensive group (2.5 and 2.5 units respectively as compared with 1.9 units, P < 0.01).

3. In the calf muscle vascular bed the patients with previous malignant hypertension had the most severe changes. Resistance at maximal dilatation was 2.4 units as compared with 1.9 units in the group with ‘benign’ hypertension (P < 0.05) and 1.6 units in the control group (P < 0.001 and P < 0.05 respectively).

4. These findings indicate structural changes in the resistance vessels of both hypertensive groups, which means that, in spite of substantial long-term lowering of blood pressure, arteriolar vascular changes remain. Accordingly, these changes may not be entirely reversible. The degree of reversibility also appears to be different in the two vascular beds studied.
Reduced Synthesis of [Arginine]Vasopressin in Spontaneously Hypertensive Rats
Authors: Rascher W. , Lang R. E. , Fink B. , Ganten D. , Unger TH. , Gross F.
Published: August 2015

1. In 12 week-old stroke-prone spontaneously hypertensive (SPSH) rats and in normotensive Wistar-Kyoto (WKY) rats plasma concentration of [arginine]vasopressin (AVP) and the AVP content in various brain areas were measured by radioimmunoassay.

2. In hydrated SPSH rats plasma AVP was lower than in WKY rats. In the hypothalamus and in the brain stem, but not in the pituitary, the content of AVP was reduced.

3. After a dehydration period of 48 h plasma AVP rose similarly in both SPSH and WKY rats. However, in the pituitary the AVP content was significantly lower in SPSH than in WKY rats. In the hypothalamus and in the brain stem, AVP content was not significantly influenced by dehydration.

4. It is concluded that in the hydrated stage the secretion of AVP and its synthesis in the hypothalamus are reduced in SPSH rats. However, the SPSH rats still respond satisfactorily to the strong stimulus of severe dehydration.
Identification of Bacterial Colonies Expressing Cloned Recombinant DNA Coding for Renin
Authors: Morris B. J. , Catanzaro D. F. , Cam G. R. , Charnock P. P. , Baker A. R. , Shine J.
Published: August 2015

1. Affinity purified anti-renin was used to detect renin-immunoreactive proteins in cloned colonies of Escherichia coli containing recombinant mouse submandibular gland cDNA inserted at the PstI site of plasmid pBR322.

2. Two colonies were detected which reacted positively with anti-renin.

3. These colonies contained a single protein that could be immunoprecipitated with anti-renin and cDNA of more than 500 base-pairs in length which was capable of inter-colony hybridization in the single-stranded form and had similar HinfI restriction sites.

4. Sequencing is being performed on the cDNA after having been subcloned in M13mp 7.1.
Effect of Captopril on the Blood Pressure and Renal Responses to Acute Saline Loading in Normal and Essential Hypertensive Subjects
Authors: Mimran A. , Ribstein J.
Published: August 2015

1. Systemic, humoral and renal responses to isotonic volume expansion (1800 ml in 3 h) were assessed in normal subjects and patients with normal renin essential hypertension before and during captopril administration.

2. Essential hypertensive subjects had a greater natriuretic and diuretic response to volume expansion than had normotensive subjects.

3. Captopril induced a fall in pre-saline mean arterial pressure more marked in hypertensive (20 ± 3 mmHg) than in normotensive subjects (9 ± 2 mmHg) and did not produce any change in sodium balance.

4. Captopril exaggerated the response of arterial pressure to volume expansion since mean arterial pressure increased more markedly after than before captopril in both normotensive (18.7 ± 3.8%) and hypertensive subjects (16.9 ± 3.7%).

5. Captopril blunted the exaggerated natriuretic response to volume expansion observed in patients with essential hypertension, whereas the renal response was unchanged in normotensive subjects.
Research Policies in Mild Hypertension and the Role of the WHO/ISH Liaison Committee
Authors: Strasser T.
Published: August 2015

1. A number of major therapeutic trials in mild hypertension were conducted from 1972 to 1980. With one exception, there was little or no coordination between the trials, although they were dealing with the same problem.

2. A Joint WHO/ISH Mild Hypertension Liaison Committee was set up after most of the trials had started. The objective of the Committee, to promote information exchange and comparisons among the trials, was attained. Certain similarities and disparities between the trials were also identified.

3. Some of the disparities proved useful because they made it possible to analyse the problem from different points of view. Others did not introduce any new elements but, on the contrary, hampered inter-trial comparability.

4. Early standardization of methodological details in such trials is essential, particularly if several studies are to investigate the same problem. This would be possible only if prior agreement were reached concerning research policy, especially in rapidly developing fields of hypertension research.
Captopril: Evaluation of Low Doses, Twice-Daily Doses and the Addition of Diuretic for the Treatment of Mild to Moderate Hypertension
Authors:   Veterans Administration Cooperative Study Group on Antihypertensive Agents, Materson Barry J.
Published: August 2015

1. We randomized 475 men whose diastolic blood pressure was 92–109 mmHg to either placebo- or captopril-treated (37.5, 75 and 150 mg/day) groups for 7 weeks.

2. After 7 weeks, the placebo-treated patients were given hydrochlorothiazide (25 mg twice daily), as were two-thirds of each captopril-treated group, and they were observed for 7 additional weeks.

3. Captopril reduced blood pressure by 12.2 ± 0.8/9.4 ± 0.4 mmHg at 7 weeks (n = 323) and captopril plus placebo by 10.3 ± 1.9/10.2 ± 0.9 at 14 weeks (n = 83); placebo by 20 ± 1.7/3.4 ± 0.8 (n = 76); captopril plus hydrochlorothiazide by 24.4 ± 1.1/16.2 ± 0.6 (n = 173). The effect of low-dose captopril was similar to that of a high dose. The effect of twice-daily captopril appeared to be equal to that of thrice-daily treatment but monitoring studies are needed to confirm this.

4. Only 15 out of 384 (3.9%) of patients were dropped from the study because of adverse effects.

5. Low-dose captopril may be useful in patients with mild to moderate hypertension.
Prevention and Reversal of Malignant Hypertension in Dahl S Rats by Nifedipine
Authors: Garthoff B. , Kazda S. , Luckhaus G. , Nash G.
Published: August 2015

1. Addition of nifedipine to a high salt diet prevented the development of malignant hypertension in the Dahl salt-sensitive strain (Brookhaven) of rats (DS rats).

2. In DS rats with a pre-existent malignant hypertension nifedipine normalized blood pressure, which then correlated with a lower incidence and degree of vasculopathy.

3. Nifedipine appeared to counteract the effect of a supposed humoral pressor agent in DS rats.
Acute Blood Pressure-Lowering Effect of Sublingual Nifedipine: A Clinical Study
Authors: Wasir Harbans S. , Rao Seshagiri P.
Published: August 2015

1. Nifedipine, a slow-channel calcium blocker, causes smooth muscle relaxation and thereby results in falls in peripheral vascular resistance and systemic arterial pressure.

2. In an uncontrolled open study nifedipine was given sublingually to 10 patients with blood pressures of 180/120 mmHg or above.

3. After a single dose of 10 mg, all patients showed a significant reduction in blood pressure within 10 min. The maximum effect was seen at around 1 h and blood pressure was reduced for up to 6 h or more.

4. Two patients with chronic renal failure and one with phaeochromocytoma also showed a similar antihypertensive response.
Effects of Myeloid Leukaemic Blast Cell Extract on Sodium Transport in Human Erythrocytes
Authors: Mir M. Afzal
Published: August 2015

1. Previous studies have shown that leukaemic plasma inhibits sodium efflux from erythrocytes. In this study the effect of an extract of myeloid leukaemic blast cells on sodium efflux was investigated.

2. Blast cell extract decreased the sodium efflux rate constant in erythrocytes from 0.395 ± sem 0.028 to 0.310 ± 0.018 (P < 0.02), whereas a leucocyte extract had no significant effect.

3. The extract had an inhibitory effect after heating at 80° C for 30 min, and in the presence of ouabain and frusemide alone or in combination.

4. These studies suggest that myeloid leukaemic blast cells contain a heat stable factor which inhibits the efflux of sodium at least in part through a pathway which is not inhibited by ouabain or frusemide.
Sex Differences of Hepatic Conjugation of Bilirubin Determine its Maximal Biliary Excretion in Non-Anaesthetized Male and Female Rats
Authors: Muraca Maurizio , De Groote Jan , Fevery Johan
Published: August 2015

1. Hepatic bilirubin UDP-glucuronosyltransferase activity was higher in female than in male rats; gonadectomy decreased enzyme activity in females and increased it in males. This sex difference in bilirubin conjugation was further used to evaluate the effect of differences in conjugation on the maximal biliary excretion of bilirubin in the non-anaesthetized rat.

2. After infusion of bilirubin, the maximal biliary excretory rate (Tm) and maximal concentration of bilirubin in bile were respectively 70% and 40% higher in female than in male rats; these values were decreased in females after ovariectomy and increased in males after orchiectomy. A linear relationship was found (r = 0.86; P < 0.001) between bilirubin Tm and hepatic bilirubin UDP-glucuronosyltransferase activity in the four groups of rats, suggesting that conjugation was the rate-limiting step for the maximal hepatic transport of bilirubin.

3. At the end of bilirubin infusion, bilirubin conjugates in serum, determined by alkaline methanolysis and high-performance liquid chromatography, ranged from 0.5 to 1.4% of total bilirubin. Therefore no significant reflux of conjugated bilirubin occurred during saturation of the hepatic transport of the pigment, once more suggesting that the secretory step was not rate-limiting.

4. The composition of bilirubin conjugates in bile was similar in the four groups of rats, despite significant differences in transferase activity. This suggests that the relative proportion of bilirubin mono- and di-conjugates in bile is affected by factors other than transferase activity alone. Relatively more monoconjugates were excreted under the bilirubin load than in basal conditions.
Whole-Body Protein Turnover before and after Resection of Colorectal Tumours
Authors: Glass R. E. , Fern E. B. , Garlick P. J.
Published: August 2015

1. The rate of whole-body nitrogen flux; protein synthesis and protein breakdown were measured in patients with colorectal cancer (Dukes A—C) just before and 12 weeks after surgical removal of the tumour. The rates were determined from the urinary excretion of 15N in ammonia and in urea over a 9 h period after an oral dose of [15N]glycine.

2. The food intake during the 2 study days was identical for individual patients. The amount each received was determined from measurement of their intake of food ad libitum on the day preceding the pre-operative study and was consumed in six equal portions every 2 h during the experimental period.

3. No significant differences in the rates of nitrogen flux, protein synthesis and protein breakdown were found before and after tumour resection, whether calculated from the excretion of 15N in ammonia or in urea. Some changes in flux, both increases and decreases, were observed in individual patients after tumour removal but these could not be related to classification of the tumour, or to the presence of pre-operative anorexia or weight loss.

4. The results suggest that the primary tumour itself does not alter the overall rate of protein metabolism in the whole body.