bluuebunny/crossref_metadata_2025 huggingface dataset:
The use of Minoxidil in the Treatment of Severe Essential Hypertension: A Report on 100 Patients
Authors: Jacomb R. G. , Brunnberg F. J.
Published: August 2015

1. One hundred patients with severe essential hypertension have been treated with minoxidil for a mean period of 8·4 months in a study involving eleven European centres. Seventy-two males and twenty-eight females were included in the group; the mean age was 55 years and the initial supine systolic and diastolic pressures averaged 212 (range 150–270) and 125 (range 90–150) mmHg respectively.

2. Reduction of supine diastolic pressure to less than 100 mmHg occurred in 94% of patients within 4 weeks. After the average follow-up period of 8·4 months the mean pressures were 151/91 mmHg. Concomitant therapy with β-receptor-blocking agents and diuretics resulted in satisfactory control of heart rate and weight gain.

3. Side effects included increased hair growth, nausea, fatigue, rash and darkening of the skin. ECG showed mainly T-wave changes and echocardiographic examination indicated improved ventricular emptying.
Treatment of Severe and Moderate Hypertension with Minoxidil: Experience in Twenty-Eight Patients
Authors: Dunea G. , Mamdani B. , Mahurkar S. D.
Published: August 2015

1. Twenty patients with severe or moderate hypertension were treated with minoxidil for 284 patient-months.

2. The blood pressure was controlled in all patients, including those refractory to maximal doses of conventional anti-hypertensive agents.

3. In patients with moderate hypertension control with minoxidil was achieved earlier and more easily than with hydrallazine.

4. Three patients developed secondary resistance and required addition of guanethidine or increased doses of diuretics.

5. Fluid retention and hypertrichosis were the main side effects with minoxidil.
Clinical and Haemodynamic Study of Minoxidil in Moderately Hypertensive Patients
Authors: Jensen H. Ærenlund , Rasmussen K. , Mosbæk N.
Published: August 2015

1. We have evaluated the effectiveness and safety of minoxidil in moderately hypertensive out-patients. Eight patients were treated with hydrochlorothiazide and minoxidil for 5 months. The only female patient developed slight, reversible facial hair growth. In the other seven patients there was a moderate decrease in blood pressure. There were only minimal side-effects. Mild exertional tachycardia and a mean increase in body weight of 0·5 kg was found, but no oedema or signs of cardiac insufficiency were observed. No abnormalities were seen during routine blood tests.

2. This study shows that minoxidil combined with a diuretic may be successfully used in treating moderately hypertensive male patients.
Treatment of Hypertension in Middle-Aged Men: A Feasibility Study in a Community
Authors: Åberg H. , Hedstrand H.
Published: August 2015

1. In a health examination survey of 2322 men, aged 49–50 years, the prevalence of hypertension was 7·5%. All men with a supine diastolic blood pressure ≥ 105 mmHg were invited to a hypertension clinic.

2. Two years' treatment in eighty-six men achieved a blood pressure reduction of 31/16 mmHg, which was maintained for a 4 years period and considered satisfactory in 80% of the subjects. Propranolol was used in more than 80% of the cases.

3. The study indicates that it is possible to obtain acceptable blood pressure control in the community.
Pharmacokinetic and Pharmacological Studies with Clonidine in Normal Subjects
Authors: Davies D. S. , Wing L. M. H. , Reid J. L. , Tippett P. , Dollery C. T.
Published: August 2015

1. A highly specific and sensitive assay based on stable isotope dilution and mass fragmentography has been developed to measure clonidine in plasma.

2. Plasma half-lives of clonidine ranged from 6·9 to 9·4 h in five normotensive subjects.

3. Plasma clonidine concentration correlated with reduction in salivary flow and degree of sedation but not with change in blood pressure.
Haemodynamic and Endocrine Changes during Antihypertensive Treatment with Clonidine and its Derivative St 600
Authors: Kho T. L. , Zaal G. A. , Wester A. , De Leeuw P. W. , Birkenhäger W. H.
Published: August 2015

1. The cardio-renal haemodynamic and endocrine effects of the anti-hypertensive agents 2-(2,6-dichlorophenylamine)-2-imidazoline hydrochloride (clonidine, St 155) and 2-(5-fluor-o-toluidine)-2-imidazoline hydrochloride (St 600) were investigated in twelve patients with essential hypertension.

2. The anti-hypertensive action of both compounds was similar and was accompanied by a reduction in heart rate and in cardiac output, total peripheral resistance being unchanged. There was no alteration in renal blood flow and glomerular filtration rate, and renal vascular resistance showed a significant decrease. Blood volume and plasma renin concentration did not change significantly. An inverse relation between changes in plasma volume and plasma aldosterone concentration was observed. In the face of similar reductions in blood pressure, no differences were observed between systemic and renal haemodynamic and endocrine responses after clonidine and St 600.
Characteristics and Prognosis for Women with Hypertension in a Community: Results of a Longitudinal Study in Göteborg, Sweden
Authors: Bengtsson C. , Lindquist O.
Published: August 2015

1. During the years 1968–69 a population study of 1462 women aged 38–60 years was carried out in Göteborg, Sweden. A total of 126 women were classified as hypertensive.

2. Hypertensive women reported a history of albuminuria and hypertension during pregnancy more often than women in the general population. Albuminuria, alterations of the eye-ground vessels and ECG changes indicating left ventricular strain were more often found in hypertensive women. Hypertensive women were on average heavier.

3. The same population sample was re-studied 6 years later. Two of the 126 women classified as hypertensive had died during the 6 years interval since the first examination, both from myocardial infarction. The death rate was similar to the population sample as a whole.
Blood Pressure and its Spontaneous Variations in a Northern Italian Population
Authors: Ambrosio G. B. , Bugaro L. , Gabaldo S. , Pigato R. , Zamboni S. , Dal Palù C.
Published: August 2015

1. Blood pressure has been measured in a random sample of 5852 subjects (both sexes, 20–64 years old). The prevalence of hypertension (blood pressure ≥ 160 mmHg and/or 95 mmHg; 150 mmHg and/or 90 mmHg under the age of 30 years) was 29·5%.

2. In a cohort of 972 detected hypertensive subjects, longitudinal changes (2 and 5 months after the initial examination) were evaluated. The phenomenon of regression toward the mean value was evident.

3. The implications of the variability of blood pressure in a community control programme of hypertension are discussed.
Reversed Diurnal Blood Pressure Rhythm in Hypertensive Pregnancies
Authors: Redman C. W. G. , Beilin L. J. , Bonnar J.
Published: August 2015

1. Reversal of the normal diurnal blood pressure pattern has been demonstrated in women with severe hypertension and renal impairment in pregnancy (pre-eclampsia).

2. Maximum arterial pressure occurred at night in these women. The phenomenon was not due to hypotensive drug therapy or posture. Patients with uncomplicated essential hypertension in pregnancy retained a normal diurnal blood pressure pattern.

3. Nocturnal hypertension in pre-eclampsia is of theoretical interest and practical importance.
Biosynthesis of Folate Polyglutamate in the Rat with Different Tracers
Authors: Reed B. , Weir D. G. , Scott J. M.
Published: August 2015

1. The recent suggestions that folate polyglutamate biosynthesis demonstrated in vivo with [3′5′9(n)-3H]folic acid is due to exchange and cannot be achieved with [2-14C]folic acid has been demonstrated to be untrue.

2. The compounds formed with both types of radioactive tracer have been shown to be folate polyglutamates from their elution position from precalibrated ion-exchange columns and their susceptibility to hydrolysis by a γ-carboxypeptidase (conjugase) from human sera.

3. By the use of the methods involving [2-14C]folic acid, reported by others to give only folate monoglutamates, we have been able to demonstrate clearly the presence of folate polyglutamates.
The Forms of Vitamin B12 on the Transcobalamins
Authors: MacDonald Caroline M. L. A. , Farquharson J. , Bessent R. G. , Adams J. F.
Published: August 2015

1. The transcobalamins from normal serum were obtained in two fractions. One contained transcobalamin I and transcobalamin III: the other contained transcobalamin II. The forms of vitamin B12 in the two fractions were then examined.

2. Methylcobalamin and adenosylcobalamin were found in both fractions. Hydroxocobalamin was found in the fraction containing transcobalamin I and transcobalamin III. Cyanocobalamin was found in both fractions in two cases, in the transcobalamin III fraction only in one case and was absent in one case.
The Role of the False Neurotransmitter Octopamine in the Hypotension of Fulminant Hepatic Failure
Authors: Trewby P. N. , Chase R. A. , Davis M. , Williams R.
Published: August 2015

1. An investigation was carried out into the mechanism of unexplained hypotension in patients with fulminant hepatic failure. The cardiac output and peripheral resistance were compared in normotensive and hypotensive patients. In addition, the serum concentration of the false neurotransmitter octopamine and the pressor response to noradrenaline, and to the indirectly acting sympathomimetic agent tyramine, were measured in hypotensive and normotensive patients with fulminant hepatic failure and in healthy subjects.

2. The cardiac output and the peripheral resistance were decreased in the hypotensive patients, and their mean heart rate was slower than in the normotensive patients. Although the serum octopamine concentration was significantly elevated in the patients compared with the control subjects, the highest octopamine concentrations were unexpectedly found in the normotensive patients and a significant positive correlation could be demonstrated between the resting blood pressure and the serum octopamine concentration. The pressor response to tyramine and noradrenaline were similar in the hypotensive patients, the normotensive patients and control subjects.

3. These results suggest that neither increased serum concentrations of the false neurotransmitter octopamine, nor end-organ insensitivity to released noradrenaline are responsible for the hypotension. A more likely explanation is toxic depression of the vasomotor centre. The opening of peripheral arteriovenous shunts, possibly as a result of endotoxaemia, might be an additional factor.
Functional and Structural Changes after Disuse of Human Muscle
Authors: Sargeant A. J. , Davies C. T. M. , Edwards R. H. T. , Maunder C. , Young A.
Published: August 2015

1. Seven patients who had suffered unilateral leg fracture were studied after removal of immobilizing plaster casts.

2. Leg volume measured anthropometrically was reduced by 12% in the injured leg (5·68 ± 1·05 litres) compared with the uninjured (6·43 ± 0·87 litres). Associated with this loss was a similar reduction in the net maximum oxygen uptake achieved in one-leg cycling, from 1·89 ± 0·21 l/min in the uninjured leg to 1·57±0·18 l/min in the injured.

3. Measured by a percutaneous needle biopsy technique, a reduction of 42% was found in the cross-sectional area of the muscle fibres sampled from the vastus lateralis of the injured compared with the uninjured leg.

4. Staining for myosin adenosine triphosphatase activity showed that both type I and II fibres were affected, being reduced respectively from 3410 to 1840 μm2 and from 3810 to 2390 μm2 cross-sectional area.

5. Possible reasons and implications are discussed for the discrepancy between the magnitude of the difference observed in the gross measurement of leg function (maximum oxygen uptake) and structure (leg volume) as compared with the cellular level (cross-sectional fibre area).
Suppression of Plasma Renin Activity by Intravenous Infusion of Antidiuretic Hormone in Man
Authors: Hesse B. , Nielsen I.
Published: August 2015

1. Ten patients on maintenance diuretic treatment received an intravenous infusion of antidiuretic hormone at a low rate for 1 h.

2. A gradual reduction in mean plasma renin activity was observed and this was significant at 60 min.

3. There was a significant correlation between the initial value and the extent of the fall in plasma renin activity. There was no consistent change in blood pressure, heart rate and blood volume.

4. The results point to an intrarenal site of action of antidiuretic hormone.
Erythrocyte Adenosine Triphosphate and 2,3-Diphosphoglycerate after Human Renal Transplantation: Dissociation from Hypophosphataemia
Authors: Barcenas C. G. , Paez P. , Uyeda K. , Peters P. C. , Hull A. R.
Published: August 2015

1. Erythrocyte 2,3-diphosphoglycerate (2,3-DPG) and adenosine triphosphate (ATP) were determined in normal individuals, uraemic patients on chronic haemodialysis and patients who underwent renal transplantation, and correlated with plasma phosphate and arterial blood pH.

2. Significant increases in the 2,3-DPG and ATP content were found in the uraemic patients and these persisted after transplantation in spite of marked hypophosphataemia.

3. No correlation was established with plasma phosphate for either of the compounds but 2,3-DPG had a significant correlation with arterial blood pH.

4. Normal values for ATP and 2,3-DPG were observed in post-transplant patients with normal haematological values. The high amounts of erythrocyte 2,3-DPG and ATP in the early post-transplant period are independent of the circulating concentration of inorganic phosphate, and might represent the response of erythrocyte glycolysis to changing arterial blood pH.
Plasma Noradrenaline Concentrations in Experimental Renovascular Hypertension in the Rat
Authors: Dargie H. J. , Franklin S. S. , Reid J. L.
Published: August 2015

1. Plasma noradrenaline concentrations and dopamine β-hydroxylase activity have been measured at various stages in the development of hypertension in the one-kidney Goldblatt rat (unilateral renal arterial constriction and contralateral nephrectomy).

2. Although plasma noradrenaline concentrations were significantly elevated from control values at 7, 14 and 28 days, plasma dopamine β-hydroxylase activity was not significantly different from control values except at 24 h.

3. These findings suggest that peripheral sympathetic activity is increased in the one-kidney Goldblatt model of experimental hypertension but that plasma dopamine β-hydroxylase activity is a poor index of this increase.

4. Both the rise in blood pressure and the rise in plasma noradrenaline concentrations were prevented by pretreatment with intracisternal 6-hydroxydopamine, suggesting that the increased sympathetic activity is at least in part centrally mediated.
Intrarenal Role of Angiotensin II in Controlling Sodium Excretion during Dehydration in Dogs
Authors: Trippodo N. C. , Hall J. E. , Lohmeier T. E. , Guyton A. C.
Published: August 2015

1. The intrarenal role of angiotensin II in controlling sodium excretion was examined in anaesthetized, dehydrated dogs by infusing the angiotensin II antagonist Sar1-Ile8-angiotensin II directly into the renal artery. Comparisons were made with dehydrated dogs receiving only sodium chloride solution intrarenally.

2. Intrarenal angiotensin II blockade resulted in significant increases in urinary sodium excretion and urine flow rate.

3. The results indicate that during the high-renin state of dehydration endogenous angiotensin II has intrarenal effects which lead to salt and water retention.
Studies on the Kinetics of Unconjugated [14C]Bilirubin Metabolism in Normal Subjects and Patients with Compensated Cirrhosis
Authors: Owens D. , Jones E. A. , Carson E. R.
Published: August 2015

1. The kinetics of unconjugated [14C]-bilirubin metabolism have been investigated and analysed in terms of a three-pool model in a group of seven normal subjects and in a group of eight cirrhotic patients who had appreciable impairment of liver cell function.

2. In the patients with cirrhosis, the plasma unconjugated bilirubin was either normal or only slightly increased but the metabolism of unconjugated bilirubin was deranged.

3. The mean volume of distribution, the mean 4 h retention, and the mean mass of the rapidly mixing pool were all significantly greater than in the normal subjects. In contrast, mean fractional clearance rate and mean estimated erythrocyte life-span were significantly less than in the normal subjects.

4. The mean fractional transfer rates and fluxes from pool 1 (rapidly mixing pool—‘plasma’) to pool 3 (‘extravascular’) and vice versa were significantly greater than the corresponding values in the normal subjects.

5. The results indicate that, in patients with compensated cirrhosis, the efficiency of the liver in extracting unconjugated bilirubin from plasma against a concentration gradient is impaired, even though the liver's capacity to conjugate bilirubin may be normal. As a consequence of the increased volume of distribution, the absolute hepatic clearance of unconjugated bilirubin is relatively well maintained.
The Assessment of Left Ventricular Ejection Fraction in Patients with Ischaemic Heart Disease by Contrast Ventriculography and Nuclear Angiography
Authors: Muir A. L. , Hannan W. J. , Brash H. M. , Baldwa V. , Miller H. C. , Ogilvie B.
Published: August 2015

1. In 18 patients with ischaemic heart disease left ventricular ejection fraction, measured by two different nuclear angiographic methods, has been compared with ejection fraction measured by single-plane contrast angiography.

2. The first nuclear angiographic technique involves detection of variation in the radioactivity from the left ventricle during the initial passage of a bolus of 99Tcm-labelled human serum albumin injected intravenously; the second is our own modification of a ‘gated’ method, which accumulates the radioactivity detected during the continuing recirculation of the plasma bound radioisotope, so presenting an ‘averaged’ ventricular volume curve.

3. Ejection fraction, measured by the ‘bolus’ method, is lower than that measured either by contrast ventriculography or by the ‘gated’ method. This may be due to a damping effect.

4. Ejection fraction measured by the ‘gated’ method is well correlated with that measured by contrast ventriculography (r = 0·89).

5. Our modification of the ‘gated’ method, which presents the changes in ventricular volume throughout the cardiac cycle, without needing computer facilities, is a useful non-invasive means for assessment of left ventricular function.
Effects of Hexachlorobenzene Feeding and Iron Overload on Enzymes of Haem Biosynthesis and Cytochrome P450 in Rat Liver
Authors: Louw M. , Neethling A. C. , Percy V. A. , Carstens M. , Shanley B. C.
Published: August 2015

1. The effect of hexachlorobenzene feeding on liver δ-aminolaevulinate synthase, uroporphyrinogen decarboxylase and cytochrome P450 was studied at various time-intervals in siderotic and non-siderotic rats.

2. In the non-siderotic group hexachlorobenzene feeding led to a progressive decrease in liver uroporphyrinogen decarboxylase activity, accompanied by a progressive increase in δ-aminolaevulinate synthase activity. Cytochrome P450 concentrations were above normal throughout but fell toward the end of the experiment.

3. Similar but more marked changes were found in the siderotic animals. The fall in uroporphyrinogen decarboxylase activity occurred earlier and was significantly greater in these animals, whereas the increase in δ-aminolaevulinate synthase activity was consistently larger. Liver cytochrome P450 concentration also rose but to a lesser extent than that in the non-siderotic rats.

4. Hexachlorobenzene-induced porphyria would seem to be attributable to inhibition or inactivation of hepatic uroporphyrinogen decarboxylase. Hepatic siderosis has a synergistic effect with hexachlorobenzene on this enzyme and may exert additional effects by promoting cytochrome P450 turnover.
Failure of Loading with Sodium Bicarbonate to Protect against Acute Renal Failure Induced by Mercuric Chloride in the Rat
Authors: Beaumont J. E. , Kotchen T. A. , Galla J. H. , Luke R. G.
Published: August 2015

1. To investigate the mechanism by which sodium loading protects against acute renal failure we compared the effects of prior chronic loading with NaCl, or with NaHCO3, on renal function after injection of HgCl2.

2. Twenty-four male Sprague-Dawley rats were divided into three groups of eight rats. One group drank isotonic NaCl solution, a second drank isotonic NaHCO3 solution and the third control group drank deionized water. Acute renal failure was induced by HgCl2 on day 9, and the rats were killed 48 h after injection.

3. Net sodium balances and plasma volumes were similar in both groups of sodium-loaded rats. After HgCl2 serum creatinine was significantly less and urinary volume was greater in NaCl-loaded than in both NaHCO3-loaded and water-drinking animals.

4. Plasma renin activity of both NaCl- and NaHCO3-loaded animals was less than that of control rats. However, renal renin content was suppressed by NaCl but not by NaHCO3 loading.

5. Loading with NaCl afforded greater protection against HgCl2-induced acute renal failure than NaHCO3. Since this difference was not related to changes in sodium balance or plasma volume before HgCl2, or plasma renin activity after HgCl2, the results support the hypothesis that intrarenal renin plays a role in the pathogenesis of HgCl2-induced acute renal failure in the rat.
The Effect of Disuse Muscular Atrophy on the Forces Generated in Dynamic Exercise
Authors: Sargeant A. J. , Davies C. T. M.
Published: August 2015

1. Six patients were studied after prolonged immobilization of an injured leg resulting in muscle atrophy.

2. The forces exerted by the atrophied and normal legs during continuous dynamic exercise (one- and two-leg cycling) were examined by a specially adapted ergometer.

3. In one-leg cycling the peak force exerted on the crank at a given work rate, the net work rate performed on the crank, and the proportion of work rate performed in leg extension and flexion phases of the cycle were the same whether the atrophied or normal limb was used.

4. Despite these similarities there was an unexplained reduction in efficiency when using the atrophied leg to perform one-leg cycling.

5. In two-leg cycling the peak force exerted at a given work rate by the atrophied leg was reduced by about 40% as compared with the normal leg, which reflected a similar reduction in the contribution of that leg to the total net work rate. Possible reasons and implications for this disproportionate sharing of work between the normal and atrophied leg are discussed.
Evidence that ‘Inactive’ Renin is Produced outside the Kidney of the Rat
Authors: Vandongen R. , Poessée Marianne , Strang K. D. , Birkenhäger W. H.
Published: August 2015

1. Inactive renin, which can be converted into an active form by acidification to pH 3·3, represents 4–63% of the total renin in rat peripheral plasma.

2. No inactive component could be found in the blood-free venous effluent of the perfused rat kidney before and after stimulation with isoprenaline.

3. This suggests a possible extrarenal source for inactive renin and may explain the presence of this component in anephric patients.
Influence of Ethanol on Non-Esterified Fatty Acid and Carbohydrate Metabolism during Exercise in Man
Authors: Juhlin-Dannfelt A. , Jorfeldt L. , Hagenfeldt L. , Hulten B.
Published: August 2015

1. The influence of ethanol administration on the metabolism of non-esterified fatty acids (NEFA) and on the utilization of blood-borne substrates and stored glycogen by leg muscles was examined in nine young healthy subjects at rest and during 40 min bicycle ergometer exercise at 50% of maximal capacity. Ethanol was administered by a constant-rate intravenous infusion (6 mmol/min), giving an arterial concentration within the range of 9·3–15·6 mmol/l. Turnover of NEFA and regional exchange were evaluated with [14C]oleic acid, and muscle metabolites were analysed from needle biopsy samples.

2. Leg blood flow was not altered by ethanol. Alanine in arterial blood was reduced by approximately 25% after ethanol administration during exercise. A slight decrease in the concentration of NEFA in arterial plasma was observed after ethanol, associated with an increase in the fractional turnover of oleic acid, indicating an increased removal of NEFA from the plasma. The rate of uptake of NEFA in the leg was only slightly decreased.

3. The total glycogen depletion in leg muscle during exercise was not influenced by ethanol. The pattern of glycogen utilization in different muscle fibres was changed by ethanol and found to be dependent on the fibre composition of the respective subject. In the control experiments, but not after ethanol administration, a negative correlation was observed between glycogen utilization during exercise and the fraction of type I fibres.

4. It is concluded that ethanol administration during exercise (a) decreases leg uptake of NEFA due to a lower concentration of NEFA in plasma, although this lower uptake is compensated by an increased fractional oxidation, (b) does not influence total glycogen depletion in leg muscle, (c) changes the pattern of glycogen utilization in different muscle fibres, (d) influences only to a small extent the energy supply to working muscles, the most predominant isolated effect being on inhibition of the lactate release.
Intracellular Potassium and Steroidogenesis of Isolated Rat Adrenal Cells: Effect of Potassium Ions and Angiotensin II on Purified Zona Glomerulosa Cells
Authors: Mackie C. M. , Simpson E. R. , Mee M. S. R. , Tait S. A. S. , Tait J. F.
Published: August 2015

1. A method involving centrifugation through phthalate ester oils is described for the rapid separation of isolated cells from suspending medium. Intracellular potassium concentrations and intracellular water space values for isolated adrenal zona glomerulosa and zona fasciculata cells are given.

2. The effects of angiotensin II and a high external potassium concentration (8·4 mmol/l) on intracellular potassium contents, intracellular water spaces and hence intracellular potassium concentrations of purified glomerulosa cells have been investigated. Corticosterone secretion was also measured. Previously reported results showing a significant increase in potassium content with high external potassium were confirmed. However, angiotensin II slightly, but significantly, decreased potassium content. No significant change in intracellular water space or intracellular potassium concentration was observed with either stimulus.

3. Both stimuli significantly increased corticosterone production. There was no correlation between the percentage increase in potassium content or concentration and the percentage increase in steroid output after stimulation with high external potassium.

4. It is concluded that angiotensin II does not stimulate steroidogenesis in adrenal glomerulosa cells by raising the intracellular potassium concentration. The small, but statistically insignificant, increase caused by high-potassium medium is unlikely to be causally linked to steroidogenesis.
Plasma Catecholamines and the Pressor Response to Sar1-Ala8-Angiotensin II in Man
Authors: McGrath B. P. , Ledingham J. G. G. , Benedict C. R.
Published: August 2015

1. The initial blood pressure response to saralasin (Sar1-Ala8-angiotensin II) infusion was examined in 15 normal subjects, eight patients with untreated essential hypertension and 65 patients established on chronic haemodialysis (including six anephric patients), and related to measurements of plasma renin activity (PRA), angiotensin II, plasma catecholamines (noradrenaline and adrenaline), blood volume and extracellular fluid volume ([35S]sulphate space or exchangeable sodium).

2. A transient rise in arterial pressure, maximum after 5–6 min, occurred in all normal subjects, patients with essential hypertension and anephric patients, and in 41 of the 59 dialysis patients with kidneys.

3. In the normal subjects, saralasin infusion resulted in a significant rise in plasma noradrenaline (mean increase 360%, P < 0·02) without change in plasma adrenaline concentration. The change in noradrenaline was significantly related to the change in mean blood pressure (P < 0·05) and was similar to the response to 5 min of a 40° head-up tilt.

4. An increase in plasma noradrenaline also occurred in dialysis patients (P < 0·005) but the change in mean blood pressure with saralasin in this group was inversely related to PRA (P < 0·001) and angiotensin II (P < 0·001), directly related to blood volume (P < 0·001), but unrelated to the change in plasma noradrenaline.

5. The pressor response to saralasin may be mediated not only by angiotensin-like action on vascular receptors but also by an action on the central or peripheral autonomic nervous system.
The Treatment of Acute Intermittent Porphyria with Laevulose
Authors: Brodie M. J. , Moore M. R. , Thompson G. G. , Goldberg A.
Published: August 2015

1. The activities of the enzymes of haem biosynthesis were studied in 23 patients with acute intermittent porphyria. The mitochondrial enzymes δ-aminolaevulinate synthase, coproporphyrinogen oxidase and ferrochelatase were measured in leucocytes and the cytosolic enzymes δ-aminolaevulinate dehydratase, porphobilinogen deaminase and uroporphyrinogen decarboxylase in erythrocytes.

2. Leucocyte δ-aminolaevulinate synthase activity was elevated (P < 0·001), with marked diminution of porphobilinogen deaminase activity (P < 0·001) and reduction in the activities of δ-aminolaevulinate dehydratase (P < 0·01) and uroporphyrinogen decarboxylase (P < 0·005).

3. A therapeutic regimen based on intravenous laevulose infusion was studied. In four patients in acute attack and one in remission laevulose treatment was associated with a fall in δ-aminolaevulinate synthase activity, a rise in porphobilinogen deaminase and uroporphyrinogen decarboxylase activities, and a fall in urinary porphyrin precursor excretion (P < 0·001). These studies provide a basis for the evaluation of the use of sugars in acute intermittent porphyria.
Effects of Renal Dopamine Receptor and β-Adrenoreceptor Blockade on Rises in Blood Angiotensin after Haemorrhage, Renal Ischaemia and Frusemide Diuresis in the Dog
Authors: Bell C. , Lang W. J.
Published: August 2015

1. In chloralose-anaesthetized dogs, central venous and arterial angiotensin (AII) levels were monitored by blood-bathed bioassay during venous haemorrhage of 20 ml/kg, acute renal ischaemia induced by suprarenal aortic stenosis and frusemide-induced diuresis.

2. Blockade of intrarenal dopamine receptors with ergometrine reduced markedly the increments in arterial AII associated with haemorrhage or suprarenal aortic stenosis, but did not consistently affect the corresponding increments in venous AII.

3. Ergometrine or renal denervation did not affect the increases of blood AII associated with frusemide diuresis.

4. Blockade of β-adrenoreceptors with propranolol, by contrast, reduced blood AII increments associated with all three procedures.

5. It is suggested that renin release during moderate haemorrhage and acute suprarenal aortic stenosis is, in the dog, partly due to activation of intrarenal dopaminergic nerves.

6. The possibility is discussed that propranolol may depress renin release in the dog by an action other than that of blocking β-adrenoreceptors.
Motion of the Rib Cage and the Abdomen in Tetraplegic Patients
Authors: Mortola J. P. , Ambrogio G. Sant'
Published: August 2015

1. We have studied the motion of the abdomen and the rib cage in patients with a transection of the lower cervical spinal cord during normal breathing both in the supine and sitting posture, and compared it with that of normal subjects.

2. In the supine posture the rib cage of a patient moves paradoxically inward, therefore his chest wall is deformed, which explains the high work of breathing.

3. During expiration, beside the recoil of the respiratory system, there is also the recoil of the deformed chest wall, toward its passive configuration, with an expansion of the rib cage above its resting position during the first part of expiration and an alteration of the expiratory flow profile.

4. In a sitting ‘relaxed’ posture the paradoxical inward motion disappears in the lower rib cage, and it is reduced but still present in the higher rib cage.

5. We conclude that contraction of the diaphragm constricts the ‘passive rib cage’, either directly through its insertions or indirectly through the reduction of intrathoracic pressure. In seated subjects the diaphragm causes some expansion of the rib cage at its lower level. Therefore the motion of the rib cage is not only related to the balance between the forces developed by the diaphragm and the intercostal muscles, but also to the diaphragm dome configuration, the geometry of the rib cage and the lung volume.
Elimination of Porcine Secretin in Pigs
Authors: Fahrenkrug J. , de Muckadell O. B. Schaffalitzky , Holst J. J.
Published: August 2015

1. The elimination of immunoreactive secretin was studied in anaesthetized pigs by using constant infusions of pure natural porcine secretin.

2. The mean metabolic clearance rate was 15·4 ml min—1 kg—1, and was independent of the level at which it was determined. The mean distribution space was 64·4 ml/kg. The half-life of secretin after termination of the infusion averaged 2·6 min.

3. During intravenous infusion of secretin in a dose of 27·8 pmol h—1 kg—1 the renal extraction was 52%. Exclusion of the kidneys increased plasma secretin concentration from 26·5 pmol/l to 47·3 pmol/l and increased the half-life to 4·4 min.

4. Exclusion of the liver during infusion of secretin in a dose of 27·8 pmol h—1 kg—1 resulted in an increment in plasma secretin concentration of 7·8 pmol/l and an increase of the half-life to 3·6 min.

5. A gradient of endogenous secretin across the liver was present but no arteriovenous difference was found across the foreleg.

6. Incubation of secretin with whole blood or serum for 20 min at 37°C did not result in any degradation of secretin.
The Metabolic Response to Galactose as a Measure of Hepatic Glucose Release in Man
Authors: Royle G. , Kettlewell M. G. W. , Ilic Vera , Williamson D. H.
Published: August 2015

1. Galactose utilization after intravenous injection was measured in fed and fasted man together with changes in blood glucose, lactate and insulin.

2. Feeding did not alter blood galactose half-life.

3. The mean increases in blood glucose and lactate were greater in the fasted subjects but their concentrations reached similar values in both fed and fasted states.

4. Plasma insulin increased after galactose in the fasted state, but there was no change in the fed state, indicating that galactose is not insulinogenic.

5. After an intravenous galactose load in the fed state insulin appears to inhibit hepatic glucose release.

6. An intravenous galactose test might be a useful measure of hepatic glucose release under different physiological and pathological conditions.
Bartter's Syndrome: Contrasting Patterns of Prostaglandin Excretion in Children and Adults
Authors: Dray F.
Published: August 2015

1. The daily urine excretion has been studied of prostaglandins (PG) E2 and F2α, as measured by radioimmunoassay, in eight children and seven adults with Bartter's syndrome.

2. Excretion of both PGE2 and PGF2α was significantly higher in the patients with Bartter's syndrome than in 17 normal children.

3. Twelve normal adults excreted significantly more PGE2 and PGF2α than did the normal children. In contrast, adults with Bartter's syndrome did not show an increase in prostaglandin excretion.
The Relation between Plasma Androstenedione, Plasma Oestrone and Androstenedione to Oestrone Conversion Rates in Postmenopausal Women with and without Fractures
Authors: Pelc B. , Marshall D. H. , Guha P. , Khan M. Y. , Nordin B. E. C.
Published: August 2015

1. Plasma androstenedione, plasma oestrone and the conversion of plasma androstenedione into oestrone were measured in 19 post-menopausal women without fractures (six of them oophorectomized) and 18 with vertebral or femoral neck fractures (four of them oophorectomized).

2. In the series as a whole, the main determinant of the plasma oestrone level was the plasma androstenedione concentration. Only in the small oophorectomized group did the variation in conversion rate make a significant contribution to the variation in plasma oestrone.

3. The conversion rates were not different as between non-fracture and fracture cases but the mean plasma androstenedione and oestrone concentrations were lower (though not significantly) in the latter.
Effect of Cyclo-Alkyl Lactamimides upon Human Pepsins and Pepsinogens
Authors: Roberts N. B. , Taylor W. H.
Published: August 2015

1. Eight cyclo-alkyl lactamimides have been investigated for potential inhibitory action upon the pepsins and pepsinogens.

2. Human pepsins 1, 3 and 5 and swine pepsin were inhibited only slightly.

3. Human and swine pepsinogens were inactivated progressively by lactamimides as the number of methylene groups in the nitrogen-containing ring increased. The most potent in activator studied was N-(cis-2-phenylcyclopentyl)azacyclotridecan-2-imine hydrochloride.

4. Substitution of benzyl and tertiary butyl groups in the N-containing ring increased the pepsinogen-inactivating property of the cyclo-alkyl lactamimides.

5. N-(cis-2-Phenylcyclopentyl)azacyclotridecan-2-imine hydrochloride may be of potential importance as a therapeutic agent in peptic ulcer, and modifications to the molecule which might increase its pepsinogen-inactivating ability are suggested.
The Role of Sodium Depletion in Hydrochlorothiazide-Induced Antidiuresis in Brattleboro Rats with Diabetes Insipidus
Authors: Shirley D. G. , Walter S. J. , Laycock J. F.
Published: August 2015

1. The mechanism of the antidiuretic effect of hydrochlorothiazide in diabetes insipidus was studied in anaesthetized Brattleboro rats with the hereditary hypothalamic form of the disease.

2. The antidiuresis caused by acute administration of hydrochlorothiazide followed an increase in sodium excretion and was associated with a significant fall in the plasma sodium concentration. There were concomitant falls in effective renal plasma flow and glomerular filtration rate.

3. When sodium depletion was prevented by adjusting the infusion of sodium chloride, the falls in plasma sodium concentration, effective renal plasma flow and glomerular filtration rate were abolished. Under these circumstances there was an increase in urine volume, which suggests that hydrochlorothiazide may inhibit fractional fluid reabsorption in the proximal convoluted tubule.

4. The results indicate that the antidiuresis caused by hydrochlorothiazide in diabetes insipidus results, at least in part, from falls in effective renal plasma flow and glomerular filtration rate. These in turn seem to be entirely secondary to the drug-induced sodium depletion.
The Metabolism of Tartrate in Man and the Rat
Authors: Chadwick V. S. , Vince A. , Killingley M. , Wrong O. M.
Published: August 2015

1. Sodium tartrate labelled with 14C was given orally and parenterally to man and rats, and by direct injection into the caecum in rats. From the differences in urinary excretion after oral and parenteral administration intestinal absorption of tartrate was calculated as 18% of the dose in man and 81% in rats. Urinary tartrate was equivalent to 14% of the dose in man and 70% in rats, the difference between absorption and urinary excretion representing metabolism in body tissues.

2. Both man and the rat excreted part of the 14C as respiratory carbon dioxide. This occurred to a small extent after parenteral injection, suggesting metabolism of tartrate by body tissues, but was greater after oral or intracaecal administration, indicating that the main site of tartrate metabolism is the intestine.

3. Several genera of intestinal bacteria were shown to liberate [14C]carbon dioxide from labelled tartrate, and in a faecal incubation system l-tartrate, the natural isomer, was metabolized five times as rapidly as d-tartrate.

4. Oral sodium l-tartrate, 1·5 mmol day—1 kg—1, was given to two subjects and was shown to alkalinize the urine like sodium salts of other organic acids which are metabolized in the body. The reduction in renal hydrogen ion excretion showed that an average of 84% of the dose was metabolized.

5. Only 5% of labelled tartrate given by mouth appeared in faeces, and pharmacological doses of unlabelled l-tartrate had little or no aperient effect.

6. No evidence of toxicity of l-tartrate was encountered.
The Interpretation of Different Measurements of Airways Obstruction in the Presence of Lung Volume Changes in Bronchial Asthma
Authors: Saunders K. B. , Rudolf M.
Published: August 2015

1. We measured changes in peak expiratory flow rate (PEFR), forced expiratory volume in 1 s (FEV1·0), airways resistance (Raw), specific conductance (sGaw), residual volume (RV), functional residual capacity (FRC) and total lung capacity (TLC) in 44 patients with asthma.

2. When asthma was induced by exercise in five patients there were large changes in volumes, but these did not obscure changes in PEFR, which adequately defined the time course of the response.

3. In 70 comparisons before and after inhalation of bronchodilator drug in 33 asthmatic subjects, the responses were classified by the size of the change in lung volumes, which showed a concordant improvement, or no change, in 61 comparisons. Despite these lung volume changes, measurement of both PEFR and FEV1·0, would have detected a bronchodilator response in all but two cases.

4. In 81 comparisons in 23 subjects over time intervals varying from 1 day to 11 months, lung volumes changed in concordance with PEFR and FEV1·0 in 59. In eight of these comparisons, measurement of lung volumes would have altered our interpretation of the changes in PEFR and FEV1·0.

5. In the same 81 comparisons changes in airways resistance were concordant with changes in PEFR and FEV1·0 on 44 occasions, with minor discordant changes in 19. We could not explain the remaining 18 cases showing major discordance between these two types of measurement of airway calibre.

6. We conclude that both FEV1·0, and PEFR should be used for detection of a bronchodilator response, and that measurement of lung volumes will rarely contribute to the interpretation. Over longer periods, lung volumes should be measured if possible. We found no practical use for routine measurement of airways resistance in patients with asthma.
Comparison of Human Myofibrillar Protein Catabolic Rate Derived from 3-Methylhistidine Excretion with Synthetic Rate from Muscle Biopsies during l-[α-15N]Lysine Infusion
Authors: McKeran R. O. , Halliday D. , Purkiss P.
Published: August 2015

1. Urine was collected in five healthy men over 10–14 days, with fasting blood samples on days 1, 5 and 10, whilst they consumed a standard creatine-free diet, which was quantitatively related to their body surface area.

2. The urinary excretion of 3-methylhistidine fell to a plateau by day 5 in all subjects. Myofibrillar protein catabolic rate calculated from the mean value of 3-methylhistidine excretion from day 5 to day 10 averaged 1·21 g day−1 kg−1 body weight. The average turnover of muscle myofibrillar protein was calculated to be 2·16%/day.

3. From a previous study using continuous intravenous infusion of l-[α-15N]lysine with serial muscle biopsies on the same subjects, the mean myofibrillar protein synthetic rate was calculated to be 0·82 g day−1 kg−1 body weight, and the mean turnover rate was 1·47%/day of total muscle myofibrillar protein.

4. The estimations of myofibrillar protein turnover rate derived from the two methods are compared and the differences discussed.
Total Body Water, Total Exchangeable Sodium and Related Variables in the Ghanaian
Authors: Addae S. Kojo , Dakubu S. , Larmie E. T. , Boatin R. , Belcher E. H.
Published: August 2015

1. Standard radioisotope dilution techniques employing [3H]water and [22Na]sodium chloride have been used to determine the total body water and total exchangeable sodium of 20 male and 10 female normal Ghanaians (Africans) aged 19–25 years.

2. Lean body mass and total body fat are calculated as a percentage of body weight; the total exchangeable sodium values have been expressed in relation to lean body mass.

3. Comparison of the data for Ghanaian subjects with published figures for Caucasian subjects of similar age shows that the Ghanaian men have much less total body fat and the women a little less total body fat than their Caucasian counterparts.

4. Total exchangeable sodium expressed in terms of lean body mass shows close agreement in both men and women.
Renal Vascular Response to Haemorrhage in the Rabbit after Pentobarbitone, Chloralose–Urethane and Ether Anaesthesia
Authors: Warren D. J. , Ledingham J. G. G.
Published: August 2015

1. Total renal blood flow and its cortical distribution were measured by the microsphere technique before and after haemorrhage in conscious rabbits, and after haemorrhage in rabbits anaesthetized with pentobarbitone, chloralose—urethane or ether.

2. The average blood loss necessary to achieve a fall in systolic blood pressure to about 65 mmHg was 101 ml in conscious rabbits and 38, 90 and 118 ml in weight-matched groups of rabbits anaesthetized with pentobarbitone, chloralose—urethane and ether respectively.

3. After haemorrhage in conscious rabbits total renal blood flow fell by 25%, this fall being confined to the superficial renal cortex.

4. In rabbits subject to haemorrhage under pentobarbitone anaesthesia renal blood flow fell by a further 23% when compared with the conscious bled rabbits. This reduction in blood flow was confined to the superficial cortex.

5. Haemorrhage in the rabbits subjected to chloralose—urethane anaesthesia caused no significant change in renal blood flow, as compared with conscious bled rabbits.

6. Haemorrhage under ether anaesthesia was associated with a further 33% fall in total renal blood flow, as compared with conscious bled rabbits. This was associated with a fall of 32% and 34% in superficial and deep cortical blood flow respectively.

7. Animals subjected to general anaesthesia may be particularly susceptible to the renal haemodynamic effects of haemorrhage.
An Evaluation of Bilirubin Kinetics with Respect to the Diagnosis of Gilbert's Syndrome
Authors: Okolicsanyi L. , Ghidini O. , Orlando R. , Cortelazzo S. , Benedetti G. , Naccarato R. , Manitto P.
Published: August 2015

1. The kinetics of the plasma disappearance of bilirubin (2 mg/kg intravenously) were studied in 106 patients with Gilbert's syndrome and in 13 normal subjects.

2. All patients had significant decreases in hepatic bilirubin clearance and transfer rates from plasma to liver, resulting in increased values for plasma retention at 4 h. The calculated value for unconjugated bilirubin production was normal in 40% of patients and increased in the remainder.

3. In 29 of the Gilbert's patients their bromosulphthalein kinetics were studied 1 week before the bilirubin test. These results were essentially normal and it was concluded that the hepatic clearance mechanisms for bilirubin and bromosulphthalein are different.

4. In 10 patients the bilirubin transport maximum (Tm) was found to be low whereas the relative storage capacity (S) was normal. Phenobarbitone treatment in four patients resulted in an increase in Tm, and S decreased in two patients and remained unchanged in the other two.

5. These results support the hypothesis that there are several variants of Gilbert's syndrome and that the bilirubin tolerance test is a useful diagnostic test.
The Organelle Pathology and Demonstration of Mitochondrial Superoxide Dismutase Deficiency in Two Patients with Dubin–Johnson–Sprinz Syndrome
Authors: Peters T. J. , Seymour Carol A.
Published: August 2015

1. Liver biopsies from two patients with the Dubin—Johnson—Sprinz syndrome were subjected to analytical subcellular fractionation by sucrose-density-gradient centrifugation and enzymic micro-assays.

2. A selective deficiency of mitochondrial superoxide dismutase has been demonstrated in these patients.

3. The significance of this enzyme deficiency is discussed in relation to the organelle pathology of the syndrome.