bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sources of Bile Pigment Overproduction in Gilbert's Syndrome: Studies with Non-Radioactive Bilirubin Kinetics and with δ-[3,5-3H]Aminolaevulinic Acid and [2-14C]Glycine
Authors: Zeneroli M. L. , Piaggi V. , Cremonini C. , Gozzi C. , Ventura E. 
Published: August 2015

1. The kinetics of non-radioactive bilirubin were investigated in 100 patients with chronic non-haemolytic unconjugated hyperbilirubinaemia and in nine normal volunteers.
2. The patients with Gilbert's syndrome were divided on the basis of a two-compartment model into two distinct groups: group 1 (74 patients) with decreased hepatic uptake and conjugation of bilirubin and a bilirubin turnover rate within the normal range, and group 2 (26 patients) having normal uptake, impaired conjugation and increased bilirubin turnover rate.
3. On the basis of these findings, studies were made of early pigment production in four patients of group 1, in six patients of group 2 and in four of the normal volunteers, with [14C]glycine and ş-[3H]aminolaevulinic acid.
4. After receiving injections of labelled haem precursors, the four patients in group 1 had a normal rate of incorporation of both tracers, whereas abnormalities in incorporation were found in group 2. Four patients showed an increase of the first component of the early peak of [14C]bilirubin as well as of the early peak of [3H]bilirubin, suggesting an increased turnover of hepatic haem. Two patients showed an increased incorporation of [14C]glycine characterized by the fusion of the two early peaks, whereas the incorporation of the δ-[3H]aminolaevulinic acid was normal, indicating the presence of a primary shunt hyperbilirubinaemia.
5. The results confirm that Gilbert's syndrome is a heterogeneous condition with respect to bilirubin turnover rate. The population of Gilbert's syndrome with increased bilirubin turnover rate comprises not only patients with an increased haem erythroid turnover, but also patients with increased metabolism of nonerythroid haem protein in the liver.
Preservation of the Hypoxic Drive to Breathing in Diabetic Autonomic Neuropathy
Authors: Calverley P. M. A. , Ewing D. J. , Campbell I. W. , Wraith P. K. , Brash H. M. , Clarke B. F. , Flenley D. C. 
Published: August 2015

1. Unexplained cardiorespiratory arrests have been reported in patients with diabetic autonomic neuropathy and these could be due to denervation of the carotid chemoreceptors.
2. We have studied the ventilatory response to transient hypoxia () during exercise in 22 male diabetic patients, six with symptomatic and cardiovascular evidence to suggest diabetic autonomic neuropathy (DAN+) and 12 without these features (DAN−).
3. There was no difference in the ventilatory response to transient hypoxia between the different groups of diabetic patients ( in DAN+ patients = −0·9 ± 0·2 litre min−1 kPa−1; in DAN− patients = −1·2 ± 0·6 litres min−1 kPa−1) even allowing for differences in the level of exercise achieved (CO2 production in DAN+ patients = 743 ± 103 ml/min; CO2 production in DAN– patients = 800 ± 144 ml/min). These results fell within our normal range for ventilatory response to transient hypoxia at this level of exercise.
4. The heart rate response to transient hypoxia varied within the groups but was significantly (P &lt; 0·05) less in the patients with established diabetic autonomic neuropathy.
5. We conclude that the peripheral chemoreceptors are intact in diabetic autonomic neuropathy and that other mechanisms must be implicated in the unexpected cardiorespiratory arrests seen in these patients.
Effect of Propranolol on Hepatic Blood Flow in Normal and Portal Hypertensive Rats
Authors: Hillon P. , Blanchet L. , Lebrec D. 
Published: August 2015

1. The effects of propranolol on heart rate, arterial pressure, portal venous pressure and fractional hepatic blood flow were studied in rats with hepatic artery ligature or with portal vein stenosis, and in sham-operated rats. The effect of propranolol on cardiac output was also studied in normal rats.
2. In rats with hepatic artery ligature or with portal vein stenosis, and in sham-operated rats, propranolol decreased heart rate and portal venous pressure significantly and did not alter arterial pressure. Propranolol decreased fractional hepatic blood flow significantly in rats with hepatic artery ligature, but did not change hepatic blood flow in rats with portal vein stenosis or in sham-operated rats.
3. We conclude therefore that: (a) propranolol decreases portal venous pressure in rats; (b) this decrease in portal venous pressure results in a reduction in portal blood flow which is related, in part, to a reduction in cardiac output; (c) propranolol does not alter hepatic blood flow in normal rats or in rats with portal hypertension.
Clinical Effects and Metabolism of Diazepam in Patients with Chronic Liver Disease
Authors: McConnell J. B. , Curry S. H. , Davis M. , Williams Roger 
Published: August 2015

1. After a fixed weight-related dose given intravenously, plasma diazepam concentrations were significantly lower in 11 cirrhotic patients than in controls matched for age and sex, in the 4 h after diazepam administration but not thereafter.
2. When measured at a single fixed time point, a greater proportion of the drug was in the unbound form in the plasma of cirrhotic patients, but non-bound diazepam concentrations were not significantly different in the two groups.
3. Several psychomotor tests showed that cirrhotic patients, although having significantly impaired liver function, did not as a group have increased sensitivity to diazepam compared with their matched controls.
4. Only those cirrhotic patients who at the time of drug administration had impaired cerebral function, as judged by baseline performance of psychomotor tests, showed increased sensitivity to the effects of intravenous diazepam.
5. Psychomotor tests, particularly the Reitan trail test, seem more useful than tests of liver function or drug metabolism for identifying those patients with liver cirrhosis at risk of excessive sedation after diazepam administration.
Low-Frequency Fatigue in Isolated Skeletal Muscles and the Effects of Methylxanthines
Authors: Jones D. A. , Howell S. , Roussos C. , Edwards R. H. T. 
Published: August 2015

1. A form of skeletal muscle fatigue was examined with isolated animal and human muscle preparations. The possibility that methylxanthines could overcome this was investigated.
2. Prolonged contractile activity resulted in a long-lasting impairment of force generation at low frequencies of stimulation at times when the force at higher frequencies had substantially recovered. This was seen with both fast-twitch and slow-twitch animal muscles and with samples of isolated human muscle.
3. The decrease in low-frequency force was due to a decrease in twitch amplitude, suggesting damage to the processes involved in excitation-contraction coupling.
4. Caffeine and theophylline at concentrations of 1 mmol/l rapidly and completely reversed the effects of this form of fatigue in both animal and human muscle preparations.
5. Agents that potentiate muscle force production could be an effective means of counteracting the effects of an important form of skeletal muscle fatigue, but a clinically useful compound would need to be more potent than the methylxanthines currently in use.
Metabolic Response in Different Muscle Types to Reduced Blood Flow during Exercise in Perfused Rat Hindlimb
Authors: Walker Paul M. , Idström Jan-Peter , Schersten Tore , Bylund-Fellenius Ann-Christin 
Published: August 2015

1. In peripheral arterial insufficiency, leg blood flow during exercise is reduced. The aim of this study was to investigate the metabolic response in different muscle types during exercise at reduced versus normal exercise blood flow.
2. A modified rat hindlimb perfusion model was used. Muscle metabolites and distribution of labelled microspheres were analysed in the soleus and the gastrocnemius muscles during exercise induced by sciatic nerve stimulation.
3. Blood flow distribution between the soleus and the gastrocnemius muscles (per unit weight) was 1·7:1 at rest, and this ratio did not change significantly during exercise at reduced flow.
4. There was a more pronounced decrease in the [phosphocreatine], the [glycogen] and the [ATP]/[ADP] ratio as well as a more pronounced increase in the [lactate] and the [lactate]/[pyruvate] ratio in the gastrocnemius muscle during exercise at reduced blood flow as compared with values obtained at normal exercise flow. In the soleus muscle the difference between the two conditions was confined to an increased [lactate]/[pyruvate] ratio.
5. The results show that a muscle composed mainly of fast-twitch fibres with a high glycolytic and low oxidative capacity is much more susceptible to a reduced exercise flow than a muscle composed of slow-twitch, oxidative fibres. It is suggested that claudicating pain is related to these metabolic changes and it is concluded that pain most probably originates in type II fibres.
Arterial Smooth Muscle Effects of Aldosterone: Action on Ionic Fluxes
Authors: Moura Anne-Marie , Worcel Manuel 
Published: August 2015

1. Aldosterone given acutely to male Wistar rats stimulated ouabain-sensitive and ouabain-insensitive 22Na efflux from tail arteries.
2. These effects of aldosterone seem to depend on the activation of specific mineralocorticoid receptors, as they are blocked by antimineralo-corticoid drugs.
3. The results suggest that aldosterone may have a physiological role in the control of vascular tone.
The Effect of Bromocriptine on Circulating Vasopressin
Authors: Robinson Bruce G. , Clifton-Bligh Phillip , Posen Solomon , Morris Brian J. 
Published: August 2015

1. The oral administration of 2·5 mg of the dopamine (3,4-dihydroxyphenethylamine) agonist bromoergocriptine enhanced the osmotically stimulated rise in plasma [arginine]vasopressin ([Arg]VP) concentrations in five normal human subjects.
2. This finding lends support to the suggestion that the osmotically induced release of [Arg]VP is under dopaminergic control in man.
Breathing Pattern during and after Smoking Cigarettes
Authors: Tobin Martin J. , Schneider Anne W. , Sackner Marvin A. 
Published: August 2015

1. The breathing patterns of ten habitual smokers were monitored in the semi-recumbent position with respiratory inductive plethysmography before and after smoking cigarettes. The subjects smoked a high-tar-content (HTC) and a low-tar-content (LTC) cigarette. The mean (±sd) values and frequency histograms of minute ventilation , tidal volume (VT), frequency (fR), inspiratory time (TI), fractional inspiratory time (TI/TTOT) and mean inspiratory flow (VT/TI) during baseline were compared with the values during and after smoking.
2. On a separate occasion, specific airway conductance (sGaw) and multiple-breath nitrogen washout were measured before and after smoking in six of the subjects.
3. One group of smokers (n = 4) had a greatly increased mean (±sd) baseline VT/TI (390 ± 39 ml/s) compared with normal non-smokers and another group (n = 6) a near normal VT/TI (246 ± 36 ml/s). The first group (‘deep inhalers’) had a significantly higher mean inhalation fraction (volume of inhaled smoke and air/vital capacity; 0·25 ± 0·05). The second group had a lower mean inhalation fraction of 0·14 ± 003 (‘moderate inhalers’).
4. VT/TI decreased to 323 ± 33 ml/s in the post-smoking period in the deep inhalers, whereas it increased to 345 ± 65 ml/s in the moderate inhalers during smoking. No systematic difference in VT/TI was noted between smoking high- and low-tar cigarettes, although the high-tar brand tended to have a greater effect on VT/TI. Deep inhalers showed a fall in VT during and after smoking. Moderate inhalers showed a decrease in TI/TTOT during and after smoking.
5. sGaw, measured in four moderate inhalers and two deep inhalers, fell in all subjects after smoking HTC (19 ± 8·7%; P &lt; 0·01) and LTC (13·9 ± 10%) cigarettes.
6. ‘Sham’ smoking with an unlit cigarette produced no change in breathing pattern.
7. In moderate inhalers, the increase in respiratory output (as reflected by increased VT/TI) combined with a reduction in TI/TTOT appears to reflect the respiratory-centre stimulant effect of nicotine directly or indirectly through broncho-constriction. This contrasts with the reduced neural drive in deep inhalers, which may relate to some overriding satiating effect of the smoking.
Seasonal Changes in Serum 25-Hydroxyvitamin D Concentrations among Asian Immigrants
Authors: Stephens W. P. , Klimiuk P. S. , Warrington S. , Taylor J. L. , Mawer E. B. 
Published: August 2015

1. The exposure of Asian immigrants to effective quantities of naturally occurring ultraviolet light was investigated by observing the increase in serum 25-hydroxyvitamin D concentrations during the summer months.
2. The seasonal increase in adult males was greater than in adult females.
3. There was a significant positive correlation between the seasonal increase and the prevailing 25-hydroxyvitamin D concentration, compatible with the view that the accumulation of inadequate stores of 25-hydroxyvitamin D during the summer months results in the low serum concentrations seen in Asian immigrants.
Dissociation between Plasma Prostaglandins E and Fα, Renin and Catecholamines in Hypertensive Patients
Authors: Lijnen P. , Fagard R. , Staessen J. , Amery A. 
Published: August 2015

1. Plasma prostaglandins (PGE and PGFα) and catecholamine concentrations, and plasma renin activity were measured during an uninterrupted graded exercise test on the bicycle ergometer in 11 hypertensive patients. Blood was withdrawn from the brachial and pulmonary artery after 30 min recumbent rest, after 15 min rest sitting and at the final work load of the exercise test, which averaged 143 ± 16.5 W.
2. Exercise did not provoke a significant change in these plasma PGE or PGFα concentrations, but a rise (P &lt; 0.001) in arterial plasma renin activity and (nor)adrenaline concentration was observed. It is thus unlikely that prostaglandins E or Fα are an important determinant of release of plasma renin during exercise.
Effects in Healthy Subjects of a New Non-Thiol-Containing Angiotensin-Converting Enzyme Inhibitor, Enalapril Maleate (MK-421)
Authors: Nakashima Mitsuyoshi , Nishijima Kenji 
Published: August 2015

1. Single doses of enalapril maleate, ranging from 2.5 to 20 mg, were given orally to 12 normotensive volunteers to determine tolerability, activity on the various components of the renin-angiotensin-aldosterone system and initial pharmacokinetics.
2. Enalapril was rapidly absorbed and maximum plasma concentrations of the diacid, the active metabolite of enalapril, occurred at 3–6 h after dosing.
3. Enalapril significantly decreased systolic blood pressure at 4–6 h after the drug and diastolic blood pressure at 3–6 h after the drug. The maximum decrease of systolic blood pressure was observed at 3–4 h, whereas the maximum decrease of diastolic blood pressure was observed at 6 h.
4. Plasma angiotensin-converting enzyme activity was significantly reduced at all doses. The reduction persisted through 24 h after dosage. Plasma renin activity significantly increased after doses of 5 mg and 20 mg. Aldosterone levels significantly decreased after doses of 10 mg and 20 mg.
5. There were no adverse clinical experiences or abnormal laboratory values noted.
Sodium Balance and Adrenergic Activity in ‘Low-Renin’ Hypertension
Authors: De Leeuw P. W. , Van Leeuwen S. J. , Van Soest G. A. W. , Birkenhäger W. H. 
Published: August 2015

1. Fifty patients with uncomplicated essential hypertension were hospitalized and put on a diet containing 55 mmol of sodium daily.
2. Blood pressure was measured at 2 h intervals and averaged for each day. On the first, second, third and seventh days blood samples were drawn for measurement of renin and catecholamines. On the basis of levels on the seventh day patients were divided into a low-renin, normal-renin and a high-renin group.
3. When on balance on their sodium-restricted diet low-renin patients had significantly higher blood pressure, but similar catecholamine levels to the other groups. Cumulative sodium loss on the seventh day was significantly greater in low-renin patients than in the others.
4. It is concluded that low-renin patients exhibit enhanced sensitivity to the effect of sodium. The low-renin state seems to be associated with more severe hypertension, rather than with a disturbance in sympathetic activity.
Effect of Cyclo-Oxygenase Inhibition on Renin, Catecholamine and Blood Pressure Responses to Haemorrhage and Captopril in Conscious Rabbits
Authors: Golub M. S. , Berger M. E. , Vlachakis N. D. , Eggena P. , Sambhi M. P. 
Published: August 2015

1. Changes in plasma renin activity, plasma noradrenaline and adrenaline, and blood pressure were evaluated after mild haemorrhage (6 ml/kg) and subsequent intravenous captopril in conscious, restrained rabbits. Two protocols were followed. In the first, control animals (n = 8) were compared with rabbits receiving indomethacin (n = 8) in their drinking water for 5 days and intravenously during the haemorrhage and captopril study. In the second protocol, animals receiving propranolol in the drinking water and intravenously (n = 7) were compared with a group (n = 7) receiving propranolol plus indomethacin.
2. Urinary prostaglandin E excretion was decreased significantly with the oral administration of indomethacin in both protocols. Plasma renin activity levels were not significantly different at baseline, but the animals receiving indomethacin had significantly (P &lt; 005) lower values after haemorrhage in both studies. The large increases in plasma renin activity after captopril were not influenced by indomethacin in either study.
3. The blood pressure response to captopril was significantly blunted in the indomethacin group in the first experiment.
4. Plasma noradrenaline and adrenaline levels were not affected by indomethacin treatment in either protocol.
5. It is concluded that the plasma renin activity response to haemorrhage in conscious rabbits is mediated in part by a cyclo-oxygenase-dependent component separable from the β-adrenoceptor. The renin response to converting enzyme inhibition is not influenced by cyclo-oxygenase inhibition. A component of the blood pressure response to captopril may involve a cyclo-oxygenase product.
Decreased Prostaglandin E2 Renal Synthesis in Women with Phaeochromocytoma
Authors: Ignatowska-Świtalska H. , Wocial B. , Filipecki S. , Januszewicz W. 
Published: August 2015

1. Urinary excretion of prostaglandins E2 and F2α were determined in 11 women with phaeochromocytoma and in 23 healthy women.
2. In patients with phaeochromocytoma a significant decrease in urinary excretion of PGE2 and a significant increase in urinary excretion of PGF2α were observed in comparison with controls.
3. Decreased urinary PGE2 and increased urinary PGF2α excretion suggest impaired renal prostaglandin synthesis or metabolism.
4. High PGF2α excretion in association with reduced PGE2 excretion may reflect enhanced activity of 9-ketoreductase, probably caused by excess catecholamines.
Different Haemodynamic Reaction Patterns during Noise Exposure in Normotensive Subjects with and without Heredity for Essential Hypertension
Authors: Andrén L. , Piros S. , Hansson L. , Herlitz H. , Jonsson O. 
Published: August 2015

1. Stimulation with noise (100 dBA) for 10 min caused a significant increase in diastolic and mean arterial pressure in normotensive subjects with and without a positive family history of hypertension.
2. The blood pressure response in the group with a positive family history of hypertension was due to a significant increase in total peripheral resistance (9%, P &lt; 0.05); no such change was seen in the group without heredity for hypertension.
3. Systolic blood pressure, heart rate, stroke volume and cardiac output did not change significantly during exposure to noise.
4. There was no difference between the groups in mean intracellular sodium concentration measured in erythrocytes.
Cerebral Blood Flow and Cerebral Metabolism in Normal and Intrauterine Growth Retarded Neonatal Piglets
Authors: Flecknell P. A. , Wootton R. , John Muriel 
Published: August 2015

1. Cerebral blood flow and cerebral metabolism were measured in conscious, normally grown neonatal piglets and in littermates which had undergone intrauterine growth retardation.
2. Cerebral blood flow was measured by the Kety-Schmidt technique using [125I]iodoantipyrine as the tracer. The tissue: blood partition coefficient of this tracer was measured in separate groups of growth retarded and normal animals. Cerebral utilization rates of glucose and oxygen were calculated from the arteriovenous concentration differences on the Fick principle.
3. The mean body weight of the growth retarded animals was about half that of their normally grown littermates, and liver weight was reduced in proportion. Brain weight was slightly but significantly lower in the growth retarded animals.
4. Cerebral blood flow was lower in the growth retarded piglets but the rates of cerebral utilization of oxygen and glucose were not significantly different in the two groups. The fractional extraction of arterial oxygen by the brain was significantly higher in the growth retarded animals.
5. The partition coefficient of ipdoantipyrine was significantly lower in the growth retarded animals, being about 75% of the normal value. It is clear that had the partition coefficients been assumed to have been the same in both groups the calculated cerebral blood flows would have been identical.
6. It is concluded that growth retarded neonatal piglets have relatively normal sized brains, with a rate of glucose and oxygen consumption that is not significantly different from normal, despite a reduction in cerebral blood flow of about 35%. Consequently the fractional extraction rate of arterial oxygen by the brain is increased from 50% to 70%.
The Reliability of the Carbon Dioxide-Rebreathing, Indirect Fick Method of Cardiac Output Determination in Patients with Pulmonary Disease
Authors: Stewart R. I. , Lewis C. M. 
Published: August 2015

1. The CO2-rebreathing indirect Fick method of cardiac-output measurement was compared with the standard invasive direct Fick method for oxygen during rest and treadmill exercise in 15 patients with pulmonary disease characterized by the common feature of expiratory-airflow limitation.
2. The correlation coefficient for all 37 determinations was 0.94 (P &lt; 0.01); in patients who had a Pa-ETco2 (arterial end-tidal Pco2 gradient) of greater than 5 mmHg, the coefficient was 0.69 (P &lt; 0.05), and in the remainder, with a normal Pa-ETco2, 0.98 (P &lt; 0.01).
3. The difference in correlation between these two latter groups is statistically significant.
4. It is concluded that the indirect method is valid in most patients with pulmonary disease, but that the correlation with the direct Fick method is significantly worse when the Pa-ETco2 exceeds 5 mmHg.