bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differentiation between the intensity of breathlessness and the distress it evokes in normal subjects during exercise
Authors: Wilson Rachel C. , Jones P. W. 
Published: August 2015

1. This study was designed to examine whether normal subjects could differentiate between the ‘intensity’ of their breathlessness and the amount of ‘distress’ it evoked, by specific wording of the instructions.
2. A preliminary study showed no significant difference between ‘distress’ score during exercise measured on two separate occasions (P = 0.3).
3. Ten subjects each performed two identical incremental cycle-ergometer exercise tests on separate occasions during which they were asked to quantify either ‘intensity’ or ‘distress’ by using modified Borg scales.
4. In all subjects there was a significant correlation (P &lt;0.001) between ‘intensity’ and minute ventilation. In eight subjects there was a significant correlation (P &lt;0.05) between ‘distress’ and minute ventilation. One subject displayed no significant correlation and one registered no distress.
5. Mean ‘intensity’ was greater than the mean ‘distress’ (P = 0.0001). The slope of ‘intensity’/minute ventilation was greater than the slope of ‘distress’/minute ventilation (P = 0.0001).
6. Within individuals there was a significant correlation beween ‘intensity’ and ‘distress’ (P &lt;0.05). There was a wide scatter in the slope of this relationship between subjects and maximum ‘intensity’ and ‘distress’ did not correlate.
7. Different elements of the breathlessness sensation could be identified and selectively measured depending on the wording of the instructions given to the subject.
8. There was a wide intersubject variation in the magnitude of both breathlessness ‘intensity’ and ‘distress’ estimates, but the differences between subjects in these two components of the sensation did not appear to follow a common pattern.
Total body calcium in patients with inflammatory bowel disease: a longitudinal study
Authors: Ryde S. J. S. , Clements D. , Evans W. D. , Motley R. , Morgan W. D. , Evans C. , Rhodes J. , Compston J. E. 
Published: August 2015

1. Serial measurements of total body calcium have been made by prompt γ-neutron activation analysis in 13 patients with inflammatory bowel disease over a mean period of 23 months. Changes in spinal trabecular bone mineral density and radial shaft bone mineral content were also assessed by using quantitative computed tomography and single photon absorptiometry, respectively.
2. The mean annual decreases (95% confidence intervals) were: total body calcium, 7.8% (−12.0 to −3.7%; P &lt;0.001); spinal trabecular bone mineral density, 2.5% (−5.0 to +0.1%; 0.05 &lt;P &lt;0.1), radial bone mineral content, 2.1% (−3.4 to −0.8%; P &lt;0.01).
3. No significant correlations were found between rates of change of the three variables. However, there were significant positive correlations between the baseline values for total body calcium and radial bone mineral content (r = 0.638, P &lt;0.05), spinal bone mineral density and radial bone mineral content (r = 0.854, P &lt;0.01), and total body calcium and spinal bone mineral density (r = 0.876, P &lt;0.001).
4. These results demonstrate rapid decreases in total body calcium in patients with inflammatory bowel disease which, in conjunction with the significant decrease in radial shaft bone mineral content, indicate increased rates of cortical bone loss. Whilst values for bone mass at different skeletal sites showed positive correlations within individuals, no relationship was found between the rates of change in bone mass at these sites.
5. The rapid bone loss observed in some subjects emphasizes the importance of early detection of osteoporosis by bone densitometry and the need for effective prophylactic measures to be established in this group of patients.
Autonomic mechanisms underlying intraocular pressure changes during insulin-induced hypoglycaemia in normal human subjects: effects of pharmacological blockade
Authors: Hepburn D. A. , Fisher B. M. , Thomson I. , Barrie T. , Frier B. M. 
Published: August 2015

1. A fall in intraocular pressure is induced by acute hypoglycaemia in humans. The role of the autonomic nervous system in mediating this response was investigated in 24 normal volunteers in whom hypoglycaemia was induced with intravenous soluble insulin, under four experimental conditions: (1) control (n = 6), (2) nonselective α-adrenoceptor blockade (phentolamine) (n = 6), (3) non-selective β-adrenoceptor blockade (propranolol) (n = 6) and (4) cholinergic blockade (atropine) (n = 6). Intraocular pressure was measured by using an applanation tonometer. In 12 subjects intraocular pressure was measured during each type of pharmacological blockade of similar duration without induction of hypoglycaemia, to assess the effects of individual antagonists.
2. In the control study intraocular pressure fell during hypoglycaemia from 15 ± 1.0 to 10 ± 1.3 mmHg (P &lt;0.01) 10 min after the autonomic reaction. β-Adrenoceptor blockade caused a reduction in intraocular pressure from 15 ± 1.1 to 9 ± 1.0 mmHg (P &lt;0.001) before the administration of insulin, and when hypoglycaemia was induced intraocular pressure decreased further to 7 ± 1.0 mmHg (P &lt;0.05, compared with immediately before insulin). A decrease in intraocular pressure of similar magnitude was observed with propranolol alone (16 ± 1.0 to 10 ± 1.0 mmHg, P &lt;0.05).
3. Cholinergic blockade had no immediate effect on intraocular pressure, and the reduction in intraocular pressure during hypoglycaemia was of similar magnitude to that observed during the control study. α-Adrenoceptor blockade did not affect basal intraocular pressure, but the small reduction induced by hypoglycaemia (from 14 ± 1.4 to 12 ± 1.1 mmHg; P = not significant) was less than the decrement observed in the control experiment. The administration of atropine or phentolamine in the absence of hypoglycaemia had no significant effect on intraocular pressure.
4. In humans the reduction of intraocular pressure induced by acute hypoglycaemia appears to be mediated principally via an α-adrenoceptor-mediated mechanism.
Measurement of whole-body protein turnover in insulin-dependent (type 1) diabetic patients during insulin withdrawal and infusion: comparison of [13C]leucine and [2H5]phenylalanine methodologies
Authors: Pacy P. J. , Thompson G. N. , Halliday D. 
Published: August 2015

1. The aims of this study were twofold: (i) to investigate the ability of a recently described [2H5]phenylalanine method for quantifying whole-body protein turnover during acute physiological perturbation; (ii) to determine specifically whether the previously observed increase in protein synthesis on insulin withdrawal in insulin-dependent (type 1) diabetic patients seen when employing the [13C]leucine technique could be corroborated by using [2H5]phenylalanine.
2. Whole-body protein turnover was measured by both the [2H5]phenylalanine and [13C]leucine primed continuous infusion methods applied simultaneously to six type I post-absorptive diabetic patients during insulin withdrawal and infusion.
3. Values were determined by the [13C]leucine method by measuring either [13C]leucine (primary pool) or α-[13C]ketoisocaproic acid (reciprocal pool) enrichment in plasma.
4. Values of whole-body protein breakdown during insulin withdrawal derived from the [2H5]phenylalanine and primary and reciprocal pool [13C]leucine models respectively were 3.54 ± 0.43, 3.85 ± 0.41 and 4.62 ± 0.44 g day−1 kg−1 (means ± SD). Insulin infusion resulted in a significant reduction (P &lt;0.02) to 3.07 ± 0.34, 3.05 ± 0.26 and 3.82 ± 0.4 g day−1 kg−1, respectively. Synthesis values fell significantly but by a smaller amount than breakdown, resulting in increased (P &lt;0.05) net protein deposition, regardless of the model used.
5. These data demonstrate that the [2H5]phenylalanine and [13C]leucine methods generate similar results both in absolute and relative terms in response to short-term insulin infusion.
6. The confirmation of increased whole-body protein synthesis during insulin withdrawal by two independent methods supports the validity of this observation.
Serum and tissue α-l-fucosidase activity in the pre-clinical and clinical stages of hepatocellular carcinoma
Authors: Hutchinson W. L. , Johnson P. J. , Du M.-Q. , Williams R. 
Published: August 2015

1. To assess the value of serum α-l-fucosidase (EC 3.2.1.51) as a marker for hepatocellular carcinoma, the activity was measured in patients with hepatocellular carcinoma and in control subjects.
2. Mean serum α-l-fucosidase activity was significantly greater in 35 patients with hepatocellular carcinoma (225 ± 69 nkat/l) than in 35 patients with cirrhosis and 20 normal subjects (134 ± 30 and 93 ± 28 nkat/l, respectively). The overlap between hepatocellular carcinoma and cirrhosis, however, was such as to severely limit any value of the enzyme as a diagnostic test.
3. In four cirrhotic patients with hepatocellular carcinoma, an increased enzyme activity was detectable in samples taken up to 66 months before the tumours were diagnosed clinically.
4. The serum activity of α-l-fucosidase fell to within the reference range after liver transplantation for hepatocellular carcinoma in three patients and in one of these a subsequent rise was associated with tumour recurrence which was diagnosed at 8 months after the rise in activity. Ineffective cytotoxic chemotherapy was also associated with a progressive rise in serum α-l-fucosidase activity.
5. α-l-fucosidase activity in tumour tissue was significantly lower than that seen in non-tumour tissue from cirrhotic patients. These reductions may represent increased transport from the tissue and may partly account for the increased serum activity found in some patients with hepatocellular carcinoma.
Effect of changes in inspiratory flow rate on cough responses to inhaled capsaicin
Authors: Barros M. J. , Zammattio S. L. , Rees P. J. 
Published: August 2015

1. Twelve non-smoking subjects inhaled capsaicin at three different inspiratory flow rates: 50, 100 and 150 litres/min. Capsaicin was delivered by a breath-actuated dosimeter; inhalations consisted of 0.21–13.6 nmol of capsaicin in doubling amounts given in random order.
2. The mean number of coughs per challenge decreased with increasing inspiratory flow rate. The difference in cough numbers were significant: 7.7 (95% confidence interval 2.5–12.8) for 50 versus 100 litres/min and 10.9 (95% confidence interval 5.0–16.9) for 100 versus 150 litres/min.
3. On a separate day, a cough threshold was measured by giving increasing doses of citric acid that were inhaled at 50 litres/min. There was a positive correlation between the sensitivity to capsaicin and the cough threshold to citric acid (r = 0.69, P = 0.01), and also between the cough latencies (r = 0.67, P = 0.02).
4. The negative relationship between the cough response and the inspiratory flow rate may be caused by increased laryngeal deposition at lower inspiratory flow rates.
5. These results are compatible with a similar anatomical distribution of cough receptors for capsaicin and citric acid.
6. These results suggest that changes in inspiratory flow rate may affect the results of cough challenges.
Effects of the Fab fragment of digoxin antibody on the natriuresis and increase in blood pressure induced by intracerebroventricular infusion of hypertonic saline solution in rats
Authors: YAMADA Kaoru , GOTO Atsuo , HUI Chen , YAGI Noriko , SUGIMOTO Tsuneaki 
Published: August 2015

1. The effects of intravenous injection of Fab fragments of anti-digoxin IgG (Digibind) on the changes in blood pressure, urine volume and urinary sodium excretion after intracerebroventricular infusion of artificial cerebrospinal fluid with normal or high sodium concentration were examined in anaesthetized rats.
2. The biological efficacy of Digibind was confirmed by experiments in vitro and in vivo, which showed that pre-treatment with Digibind completely abolished or significantly attenuated the aortic contractile response or pressor response to digoxin in guinea-pigs.
3. Infusion of high-sodium cerebrospinal fluid, but not normal-sodium cerebrospinal fluid, into the lateral brain ventricle of rats caused marked increases in blood pressure, urine volume and urinary sodium excretion.
4. Digibind did not significantly affect the increases in blood pressure, urine volume and urinary sodium excretion caused by intracerebroventricular infusion of high-sodium cerebrospinal fluid.
5. Digoxin-like immunoreactive factor may play a minor role, if any, in central nervous system-induced natriuresis in rats.
Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation
Authors: Harris Roger C. , Söderlund Karin , Hultman Eric 
Published: August 2015

1. The present study was undertaken to test whether creatine given as a supplement to normal subjects was absorbed, and if continued resulted in an increase in the total creatine pool in muscle. An additional effect of exercise upon uptake into muscle was also investigated.
2. Low doses (1 g of creatine monohydrate or less in water) produced only a modest rise in the plasma creatine concentration, whereas 5 g resulted in a mean peak after 1 h of 795 (sd 104) μmol/l in three subjects weighing 76–87 kg. Repeated dosing with 5 g every 2 h sustained the plasma concentration at around 1000 μmol/l. A single 5 g dose corresponds to the creatine content of 1.1 kg of fresh, uncooked steak.
3. Supplementation with 5 g of creatine monohydrate, four or six times a day for 2 or more days resulted in a significant increase in the total creatine content of the quadriceps femoris muscle measured in 17 subjects. This was greatest in subjects with a low initial total creatine content and the effect was to raise the content in these subjects closer to the upper limit of the normal range. In some the increase was as much as 50%.
4. Uptake into muscle was greatest during the first 2 days of supplementation accounting for 32% of the dose administered in three subjects receiving 6 × 5 g of creatine monohydrate/day. In these subjects renal excretion was 40, 61 and 68% of the creatine dose over the first 3 days. Approximately 20% or more of the creatine taken up was measured as phosphocreatine. No changes were apparent in the muscle ATP content.
5. No side effects of creatine supplementation were noted.
6. One hour of hard exercise per day using one leg augmented the increase in the total creatine content of the exercised leg, but had no effect in the collateral. In these subjects the mean total creatine content increased from 118.1 (sd 3.0) mmol/kg dry muscle before supplementation to 148.5 (sd 5.2) in the control leg, and to 162.2 (sd 12.5) in the exercised leg. Supplementation and exercise resulted in a total creatine content in one subject of 182.8 mmol/kg dry muscle, of which 112.0 mmol/kg dry muscle was in the form of phosphocreatine.
Glucose-6-phosphatase in normal adult human intestinal mucosa
Authors: Pears John , Jung Roland T. , Jankowski John , Waddell Ian D. , Burchell Ann 
Published: August 2015

1. The existence of specific glucose-6-phosphatase activity in human intestinal mucosa has been somewhat controversial.
2. We have demonstrated the presence of low levels of specific glucose-6-phosphatase activity in normal human adult intestinal mucosa. Activity was found in oesophagus, stomach, duodenum and colon.
3. Immunoblot analysis using antibodies monospecific for the 36.5 kDa liver glucose-6-phosphatase catalytic subunit demonstrated that intestinal mucosa contains low levels of the glucose-6-phosphatase enzyme protein.
4. The low levels of activity together with problems of proteolysis make human intestinal biopsies unsuitable for use in the diagnosis of type 1 glycogen-storage disease.
Dopamine and the Kidney: Ten Years on
Authors: Lee M. R. 
Published: August 2015

Ten years ago the Editorial Board of Clinical Science invited me to write an Editorial Review on dopamine and the kidney. The result was published in 1982 in Volume 62 [1]. It was my hope that it would serve to stimulate other investigators to take up this area of renal physiology and pharmacology and to help to solve some of the problems left unanswered at that time. Since 1982 much has happened: there have been major successes, such as the delineation of the renal and adrenal dopamine receptors, and some relative failures, such as the lack of development of clinically useful peripheral dopamine agonists for use in hypertension and congestive cardiac failure. Nevertheless, continuous progress has been made and it is my task in this Review to try to describe this general advance while not omitting remaining areas of uncertainty.
The areas which I will undertake to describe are:
1. The renal receptors for dopamine. 2. The source of dopamine in the urine and its formation in the kidney. 3. The actions of dopamine upon the kidney. 4. The interaction of renal dopamine with other substances. 5. Dopamine formation in hypertensive and oedematous states. 6. The search for specific peripheral dopaminergic agonists of therapeutic utility. 7. Final conclusions and unanswered questions.
Effects of Oral Alcohol on Superior Mesenteric Artery Blood Flow in Normal Man, Horizontal and Tilted
Authors: Maule S. , Chaudhuri K. Ray , Thomaides T. , Pavitt D. , McCleery J. , Mathias C. J. 
Published: August 2015

1. The cardiovascular effects of oral alcohol (0.5 g/kg body weight diluted to 300 ml in sugar-free orange juice) were compared with those of placebo in 10 normal subjects. Measurements were made while the subjects were supine and horizontal for 45 min and after 10 min of 45° head-up tilt.
2. After alcohol, plasma alcohol levels rose from 1.9 ± 1.3 to 61.6 ± 6.5 mg/100 ml. After placebo, plasma alcohol levels did not increase. After alcohol and placebo, supine blood pressure was unchanged; heart rate, both supine and during tilt, rose after alcohol only.
3. After alcohol, superior mesenteric artery and digital skin blood flow increased and calculated vascular resistances fell. There was no change after placebo.
4. Forearm blood flow, forearm vascular resistance and cardiac index did not change in either phase, except for a fall in cardiac index during tilt but only after alcohol.
5. In conclusion, the acute ingestion of 0.5 g of alcohol/kg body weight in normal subjects raised heart rate and actively dilated the superior mesenteric artery and digital skin vessels. There was no effect on blood pressure, cardiac output and skeletal muscle vascular tone. During head-up tilt after alcohol, there was a tendency for blood pressure to fall with a compensatory rise in heart rate.
Increased Whole Body Protein Breakdown Predominates over Increased Whole Body Protein Synthesis in Multiple Organ Failure
Authors: Arnold J. , Campbell I. T. , Samuels Therese A. , Devlin J. C. , Green Ceri J. , Hipkin L. J. , MacDonald I. A. , Scrimgeour C. M. , Smith K. , Rennie M.J. 
Published: August 2015

1. Whole body protein turnover was measured using a primed-constant infusion of L-[1−13C]leucine with measurement of breath 13CO2 production and plasma 13C α-ketoisocaproate enrichment. Ten fasting patients, requiring mechanical ventilation and suffering from multiple organ failure, and six healthy control subjects were studied.
2. Protein breakdown and leucine removal from the plasma for protein synthesis were significantly higher in the patients than in the control subjects (P &lt;0.01). In addition, leucine oxidation was almost 75% higher in the patients than in the healthy control subjects (P &lt;0.05).
3. Plasma concentrations of glucose, insulin and growth hormone were not different between the two groups, but those of glucagon (not significant), noradrenaline (P &lt;0.05) and cortisol (P &lt;0.01) were almost two- and three-fold higher in the patients than in the control subjects.
4. Mean energy expenditure, measured by indirect calorimetry, was 30% higher in the patients than in the healthy control subjects (P &lt;0.01).
5. Combining the data from both groups of subjects and using multiple regression analysis, cortisol was found to be the most significant predictor of (i) protein breakdown (48% of variance explained), (ii) leucine oxidation (69%) and (iii) hourly energy expenditure (54%).
6. The present investigation using [13C]leucine tracer methods demonstrated, in patients with multiple organ failure, that whole body protein breakdown and synthesis increased concomitantly and were twice as high as rates measured in healthy control subjects. Of the hormones measured in the present study, Cortisol appears to have the most significant effect on whole body protein turnover.
Estimation of the Hepatic Extraction Ratio of Indocyanine Green in Swine
Authors: Kisor David F. , Frye Reginald F. , Kudsk Kenneth A. 
Published: August 2015

1. The hepatic extraction ratio of Indocyanine Green was measured directly by trans-hepatic catheterization in 14 outbred swine (eight well-fed, six malnourished). A specific two-compartment pharmacokinetic model was fitted to the arterial Indocyanine Green concentration-time data and used to estimate the hepatic extraction ratio of Indocyanine Green.
2. The specific two-compartment pharmacokinetic model was modified to represent more accurately the physiological process of Indocyanine Green removal. Simulations were performed using this new model to estimate the hepatic extraction ratio of Indocyanine Green in the swine.
3. Similarly to previous findings, our data showed that the original model consistently overestimated the hepatic extraction ratio of Indocyanine Green (i.e. the model estimate was compared with the true, directly measured value).
4. The comparison of the modified model and the original model clearly indicates the reason for the overprediction of the hepatic extraction ratio of Indocyanine Green by the latter. The simulations using the new model indicate that the percentage of binding of Indocyanine Green to its transport protein (glutathione S-transferase) for removal in the bile will affect the estimation of the hepatic extraction ratio of Indocyanine Green. Thus, the amount of Indocyanine Green available for removal is less than that assumed by the original model.