bluuebunny/crossref_metadata_2025_split huggingface dataset:
Paradoxical forearm vasodilatation and haemodynamic improvement during cardiopulmonary baroreceptor unloading in patients with congestive heart failure
Authors: Nishian Katsuhiko , Kawashima Seinosuke , Iwasaki Tadaaki 
Published: August 2015

1. To examine the contribution of paradoxical reflex forearm vasodilatation during unloading of cardiopulmonary baroreceptors to systemic haemodynamics, the responses of central and peripheral haemodynamics during lower-body negative pressure were measured in 24 patients with chronic congestive heart failure (New York Heart Association functional class II-IV) and were compared with those of 10 normal subjects.
2. Lower-body negative pressure of less than −20 mmHg caused a significant forearm vasoconstriction in normal subjects but not in patients with congestive heart failure. In the individual cases, however, eight patients (subgroup A) had a significant forearm vasoconstriction, whereas 10 patients (subgroup B) had a paradoxical forearm vasodilatation. The remaining six patients had a blunted forearm vascular response. Baseline pulmonary capillary wedge pressure (26 ± 3 versus 20 ± 1 mmHg, means ± SEM) and left ventricular wall stress in end-diastole (57 ± 6 versus 37 ± 4 g/cm2) were significantly (P &lt;0.05) higher in subgroup B than in subgroup A.
3. During lower-body negative pressure of −20 mmHg, the plasma level of noradrenaline, systemic vascular resistance and cardiac index did not change significantly in subgroup A. In subgroup B, however, during this orthostatic stimulus systemic vascular resistance fell significantly from a baseline value of 2023 ± 109 to 1740 ± 110 dyns−1 cm−5 (P &lt;0.01) and cardiac index increased significantly from a baseline value of 2.0 ± 0.1 to 2.5 ± 0.21 min−1 m−2 (P &lt;0.01) despite there being no significant change in the plasma level of noradrenaline.
4. After treatment, a second bout of lower-body negative pressure was applied to seven patients in subgroup B. The forearm vascular response to the second bout of lower-body negative pressure was normalized.
5. These data suggest that the patients with more severe heart failure show a paradoxical forearm vasodilatation during mild lower-body negative pressure and that this altered cardiopulmonary baroreflex control of the circulation serves to improve the depressed cardiac performance.
Chronic insulin treatment in rats: Evidence against a role for insulin as a pressor agent
Authors: Vargas Félix , Sabio José Mario , Castillo Miguel Angel , De Dios Luna Juan , Haro José Manuel , García Del Río Cipriano 
Published: August 2015

1. The present study was undertaken to test whether insulin acts as a pressor agent and causes hypertension in rats.
2. Insulin at doses of 10 or 100 units day−1 kg−1 was administered daily by subcutaneous injection to normal rats for 6 weeks. As it has been suggested that sodium retention plays a major role in the putative hypertensive activity of this hormone, insulin was also administered to saline- (1% NaCl) drinking rats according to the same protocol. Water- and saline-drinking rats served as controls.
3. After 6 weeks of insulin treatment, the mean arterial blood pressure did not increase in any of the insulin-treated or the insulin-salt-treated groups. However, in both insulin-salt-treated groups, absolute and relative ventricular and renal hypertrophy with increased ventricular water content as well as increased urine output with reduced osmolality were observed.
4. All insulin-treated groups showed increased plasma levels of glucose, insulin and antidiuretic hormone when compared with their respective controls.
5. These results demonstrate that chronic insulin treatment did not increase blood pressure in rats, even when drinking water was supplemented with NaCl, and suggest that a polyuria-polydipsia syndrome was present in both insulin-salt-treated groups. Moreover, increased plasma levels of antidiuretic hormone were observed in all insulin-treated groups.
Cerebrospinal fluid levels of substance P and calcitonin-gene-related peptide: Correlation with sural nerve levels and neuropathic signs in sensory diabetic polyneuropathy
Authors: Tsigos C. , Diemel L. T. , White A. , Tomlinson D. R. , Young R. J. 
Published: August 2015

1. Lumbar spinal substance P and calcitonin-gene-related peptide derive from spillage out of the dorsal horns associated with activity of small primary sensory afferents (C- and Aδ-fibres). Cerebrospinal fluid and sural nerve levels of substance P and calcitonin-gene-related peptide have been measured in patients with diabetic polyneuropathy to determine whether differences in small primary sensory afferent activity are related to the presence or absence of painful symptoms.
2. Calcitonin-gene-related peptide was undetectable in the cerebrospinal fluid of the majority of diabetic patients (14 out of 22); it was lower overall in diabetic patients as compared with control subjects (P &lt;0.01), it was lower in those diabetic patients with painless neuropathy (100% undetectable) as compared with those with painful neuropathy (50% undetectable; P &lt;0.05) and it correlated conversely with warming threshold (r = 0.50; P &lt;0.01).
3. Substance P showed no overall numerical inter-group differences or correlation with other measured variables, but six diabetic patients as compared with one control subject had undetectable cerebrospinal fluid levels and the proportion of patients with undetectable levels was higher in the group with painless neuropathy than in the group with painful neuropathy (P &lt;0.05).
4. The levels of each peptide in cerebrospinal fluid correlated with its equivalent in sural nerve (P &lt;0.01 for calcitonin-gene-related peptide and P &lt;0.03 for substance P). Calcitonin-gene-related peptide correlated with substance P in the sural nerve (r = 0.84; P &lt;0.002) and in the cerebrospinal fluid (r = 0.30; P &lt;0.03).
5. We conclude that in sensory diabetic polyneuropathy the lumbar cerebrospinal fluid levels of substance P and calcitonin-gene-related peptide relate directly to their levels in sural nerve and appear to be reduced in the painless compared with the painful syndrome, suggesting a relatively spared and/or more active primary sensory afferent fibre population in the latter.
Normal values for handgrip strength in 920 men and women aged over 65 years, and longitudinal changes over 4 years in 620 survivors
Authors: Bassey E. J. , Harries U. J. 
Published: August 2015

1. The maximal grip strength of the hand has been measured in a random sample of 359 men and 561 women aged over 65 years living in their own homes. The response rate was 80% from a representative demographic area of the U.K. Measurements were made of body mass, skeletal size (demispan) and grip strength. Grip strength was measured using a custom-built strain-gauged dynamometer. The best of three attempts was taken as definitive. A structured questionnaire was used to obtain information about customary activity, use of handgrip muscles, health and psychological well-being. This was repeated with 620 survivors 4 years later.
2. The results for strength were normally distributed. The right hand was 10% stronger than the left and men had twice the strength of women. Strength was significantly related to skeletal size and in men to body mass. The gender difference was only partly accounted for by skeletal size and women were substantially disadvantaged in terms of their strength/body mass ratio.
3. There was a significant decline in strength with age of 2%/year for men and women. Strength was also significantly related to customary activity, reported use of the hands and psychological and physical health.
4. After 4 years 620 survivors were re-measured. Grip strength had declined by 12% in men and 19% in women and these losses were significantly related to age. A significant decline was also found in reported use, customary activity and health scores, and in women in body mass and psychological health. The loss of strength was significantly related to the decline in reported use of the hands but not to the other losses.
5. It is concluded that loss of strength over time in old age may be seriously underestimated by cross-sectional studies, especially in women; and that the loss is consistently and predominantly related to lack of use, rather than loss of health.
Antibodies to Human Recombinant Lipocortin-L in Inflammatory Bowel Disease
Authors: Stevens T. R. J. , Smith S. F. , Rampton D. S. 
Published: August 2015

1. Corticosteroid drugs are widely employed for the treatment of active inflammatory bowel disease. Not all patients receiving corticosteroid treatment, however, respond satisfactorily, their disease either remaining active in spite of continued treatment, or relapsing upon corticosteroid withdrawal. Raised levels of autoantibodies to lipocortin-I, a corticosteroid-inducible protein with anti-inflammatory activity in vitro, in patients receiving chronic oral corticosteroid therapy have been associated with poor clinical response in rheumatoid arthritis.
2. To determine whether a similar mechanism is responsible for the variable clinical response to corticosteroids in inflammatory bowel disease, we have measured circulating lipocortin-I antibody levels in sera from affected patients and related them to disease activity, treatment and subsequent outcome.
3. IgM, but not IgG, lipocortin-I antibody levels were elevated in patients with ulcerative colitis and Crohn's disease compared with healthy control subjects. In patients with Crohn's disease not taking corticosteroids, IgM lipocortin-I antibody levels were directly related to disease activity scored clinically.
4. IgM lipocortin-I antibody levels were higher in patients receiving sulphasalazine or no treatment and in patients receiving corticosteroids who responded to treatment within 2 months (steroid responders) than in those patients undergoing long-term corticosteroid therapy because of continued disease activity or repeated relapse on corticosteroid withdrawal (steroid non-responders).
5. The high levels of IgM lipocortin-I antibodies in patients with inflammatory bowel disease not taking corticosteroids provides further evidence of disturbed immunity in inflammatory bowel disease. The low levels of IgM lipocortin-I antibody in patients undergoing long-term corticosteroid therapy (steroid nonresponders) contrasts with previous findings in patients with rheumatoid arthritis and might reflect corticosteroid-induced antibody suppression and/or depressed production of endogenous lipocortin-I antigen.
Changes in Sodium Transport during the Human Menstrual Cycle and Pregnancy
Authors: Webb G. D. , Ashmead G. G. , Al-Mahdi S. , Auletta F. J. , McLaughlin M. K. 
Published: August 2015

1. We have studied the transport of Na+ and K+ by erythrocytes during the follicular and luteal phases of the human menstrual cycle, and in pregnant compared with non-pregnant women. Venous blood was drawn from 10 healthy young women (not taking any medication or hormones) 1-2 days after menstruation and from the same women 7-9 days after ovulation. For the pregnancy part of the study, blood was drawn from eight other normotensive non-pregnant women and from eight age-matched normotensive pregnant women (36-43 weeks gestation).
2. Intracellular erythrocyte and plasma Na+ and K+ concentrations were measured by flame photometry. The increase in the intracellular Na+ concentration during a 1 h 37°C incubation of fresh whole blood with 0.2 mmol/l ouabain (compared with no ouabain) was measured to determine the rate of active Na+ efflux. The Na+-K+ pump rate constant was calculated by dividing the active Na+ efflux rate by the intracellular Na+ concentration.
3. In fresh blood, the intracellular erythrocyte Na+ concentration (P &lt; 0.002) and the plasma K+ concentration (P &lt; 0.01) were both lower in pregnant than in non-pregnant women. The Na+-K+ pump rate constant was higher (P &lt; 0.02) during the luteal phase than during the follicular phase, and in pregnant compared with non-pregnant women.
4. We conclude that short-acting hormones in the plasma most probably account for the changes in the Na+-K+ pump rate constant during the menstrual cycle.
In the Groove: The Fine Detail of Antigen Presentation to Cytotoxic T Lymphocytes
Authors: Moots Robert J. 
Published: August 2015

1. A panel of cells designed to express normal or mutated human HLA-A0201 was constructed and used to investigate the interactions between the peptide antigen, class I major histocompatibility complex, CD8 and cytotoxic T lymphocyte antigen receptor.
2. Analysis of the extensive data generated has revealed that the optimum peptide presented to cytotoxic T lymphocytes by HLA-A0201 contains nine amino acids. It lies in the peptide-binding groove of the class I molecule, orientated from N- to C-termini, and its detailed position within the groove has been deduced. The roles of individual residues in the class I molecule in antigen presentation are described, and the site of the ligand on target cells for interaction with CD8 on cytotoxic T lymphocytes is located.
Repeatability of Transcranial Doppler Measurements of Arterial Blood Flow Velocities in Healthy Subjects
Authors: Demolis Pierre , Chalon Stephan , Giudicelli Jean-François 
Published: August 2015

1. Transcranial Doppler measurements of the mean blood flow velocity and the resistance index in the middle cerebral artery are used to assess cerebral haemodynamics. The prerequisite for the use of these parameters in clinical pharmacology studies is an evaluation of their repeatability and spontaneous variation with time.
2. Repeatability of transcranial Doppler measurements of mean blood flow velocity and resistance index was investigated in healthy subjects by calculation of the repeatability coefficient as defined by the British Standards Institution. Intra-observer repeatability (comparison of two successive determinations by one observer, n = 30 subjects), between-observer repeatability (comparison of two successive measurements each performed by a different observer, n = 30) and long-term repeatability (comparison of two determinations performed at the same hour with a 1 week interval by one observer, n = 14) were assessed. In addition, the spontaneous evolution with time of mean blood flow velocity and resistance index was determined over an 8 h period (n = 14).
3. Repeatability coefficients for intra-observer repeatability, between-observer repeatability and long-term repeatability were 4.83, 4.59 and 3.32 cm/s for mean blood flow velocity (normal value = 61.2 ± 10.2 cm/s) and 2.62, 3.12 and 3.49% for resistance index, respectively (normal value = 53.6 ± 5.9%), indicating that transcranial Doppler measurements are repeatable enough to be used over periods of time of up to 1 week in clinical pharmacology studies.
4. Finally, a time effect was detected for mean blood flow velocity, indicating that this parameter undergoes diurnal variation.
Iso-Oncotic Volume Expansion in the Nephrotic Syndrome
Authors: Rabelink Ton J. , Bijlsma Joost A. , Koomans Hein A. 
Published: August 2015

1. In previous studies we found that albumin infusions caused only a modest natriuresis in the nephrotic syndrome, suggesting that hypovolaemia played no part in the sodium retention of these patients. However, this finding was inconclusive, since the hyperoncocity of the infused albumin probably opposed sodium excretion.
2. In the present study, we examined the effect of sustained (68 h) plasma volume expansion (+18%), by means of iso-oncotic albumin infusions, on renal function, blood pressure, humoral factors and sodium balance.
3. Plasma atrial natriuretic peptide levels increased almost threefold and renin-angiotensin system activity was suppressed. Glomerular filtration rate remained unchanged, whereas estimated renal plasma flow increased, resulting in a further decrease in filtration fraction.
4. The increase in plasma volume expansion was accompanied by a modest increase in sodium excretion, which, however, was less than the amount of sodium daily infused with the albumin solutions and consumed with the diet, so that net sodium was retained.
5. This observation supports the concept that an intrinsic renal defect causes the sodium retention in the nephrotic syndrome, and argues against the therapeutic use of albumin infusions.
A Method for the Continuous Measurement and Display of Pulmonary Resistance in Man
Authors: Lane R. , Freedman S. , Guz A. 
Published: August 2015

1. We have validated a method for the continuous display and ‘on-line’ measurement of total pulmonary resistance in man, using a hybrid digital/analog computer.
2. The basic variables, which are measured by standard techniques, are flow rate of the mouth (V̇) and oesophageal pressure (Poes), and these are the only analog inputs necessary to the computer.
3. Resistance (RL, cont) is calculated continuously as: RL, cont = (Poes - V/C)/V̇ where V is tidal volume and C is the dynamic compliance. RL, cont is continuously displayed as an analog signal on an oscilloscope.
4. Changes in resistance, measured by this method over a wide range of values in three subjects, showed an almost exact correlation with those measured by a standard method (Mead-Whittenberger).
Effect of Chronic Smoking on Endothelium-Dependent Vascular Relaxation in Humans
Authors: Jacobs Marie-Cécile , Lenders Jacques W. M. , Kapma Jan A. , Smits Paul , Thien Theo 
Published: August 2015

1. Cigarette smoking is one of the major risk factors for the development of atherosclerosis. It is not clear, however, whether chronic cigarette smoking impairs the normal physiological function of the endothelium before the development of morphological vascular lesions. To test this, we investigated endothelium-dependent vascular relaxation in young habitual smoking subjects.
2. In 11 non-smokers and 10 habitual smokers we measured the changes in bilateral forearm blood flow, arterial blood pressure and forearm vascular resistance (ratio between mean arterial blood pressure and forearm blood flow) during three interventions: postocclusive forearm hyperaemia, intrabrachial infusion of methacholine which causes vasodilatation by stimulating the release of endothelium-dependent relaxing factor, and intrabrachial infusion of sodium nitroprusside which causes vasodilatation independently from the endothelium by a direct effect on the vascular smooth muscle wall.
3. During infusion of the highest dose of methacholine, forearm vascular resistance decreased by 91.7 ± 1.4% in the smokers and by 89.9 ± 1.8% in the non-smokers. During infusion of sodium nitroprusside, forearm vascular resistance decreased by 80.0 ± 3.8% in the smokers as compared with 80.7 ± 6.1% in the non-smokers. There was no difference in basal forearm vascular resistance or in post-ischaemic reactive hyperaemia between smokers and non-smokers. Thus, vasodilatation induced by both methacholine and sodium nitroprusside was not significantly different between smokers and non-smokers.
4. We conclude that in young habitual cigarette smokers the endothelium-dependent vasodilatation in the forearm seems to be preserved, suggesting that habitual smoking does not result in permanent endothelial dysfunction in the human forearm.
Reduced Renal Papillary Plasma Flow in Non-Ascitic Cirrhotic Rats
Authors: Atuchá Noemí M. , Quesada Tomás , Garcia-Estañ Joaquín 
Published: August 2015

1. The purpose of the present investigation was to determine whether an abnormality of the renal papillary circulation is present in a well-established model of cirrhosis without ascites (carbon tetrachloride/phenobarbital).
2. Compared with the control animals, cirrhotic rats showed a reduced diuretic (61.0 ±5.1 versus 18.0 ±2.5%) and natriuretic (67.8 ±8.3 versus 29.6 ±3.6%) response to a volume expansion (3% body weight infusion of 0.9% NaCl). The volume expansion-induced increase in renal interstitial hydrostatic pressure was also blunted in the cirrhotic rats (control 9.3 ±0.9 versus cirrhotic 6.1±1.0 mmHg) and there were no differences in mean arterial blood pressure, renal blood flow or glomerular filtration rate between control and cirrhotic animals.
3. Papillary plasma flow was determined by the 125I-albumin accumulation technique and expressed as mlmin−1100 g−1. In the basal state, papillary plasma flow was significantly lower in cirrhotic rats (59.1 ±4.4, n = 9) than in the control animals (81.8 ±6.9, n = 9). An isotonic saline expansion similar to the one described above significantly increased papillary plasma flow in control rats (108.4±9.1, n = 7) but did not change it in cirrhotic rats (60.2 ±4.9, n = 6).
4. Our results indicate the existence of a selective alteration in the renal papillary circulation in cirrhotic rats, both in the basal state and after a well-established vasodilatory stimulus. The reduced papillary plasma flow of the cirrhotic animals, probably mediated through changes in renal interstitial hydrostatic pressure, may participate in the sodium and water retention that precedes the development of ascites and may be an important mechanism mediating the blunted renal response to extracellular volume expansion.
Haemodynamic and Hormonal Responses to Losartan (DuP753/MK954) Infusion during Cardiac Catheterization in Conscious Salt-Deplete Dogs
Authors: MacFadyen R. J. , Tree M. , Lever A. F. , Reid J. L. 
Published: August 2015

1. Haemodynamic and hormonal responses to infused angiotensin II were studied in conscious salt-deplete dogs during infusion of D-glucose or losartan (DuP753/MK954).
2. Mean arterial pressure (118±13mmHg) fell rapidly after losartan (60 min 106±18 mmHg) with a rise in heart rate (107±16 beats/min) from baseline (98±17 beats/min). Pressor responses to angiotensin II during D-glucose infusion (6 ng min−1 kg−1, 99±10 mmHg; 18 ng min−1 kg−1, 140±15 mmHg; 54 ng min−1 kg−1, 157±12 mmHg; 162 ng min−1 kg−1, 178±14 mmHg) showed a parallel shift during losartan infusion with very similar pressures in response to higher rates of angiotensin II infusion (54 ng min−1 kg−1,108 ± 17 mmHg;162 ng min−1 kg−1 138±14 mmHg; 486 ng min−1 kg−1, 155±14 mmHg; 1458 ng min−1 kg−1, 177 ± 12 mmHg). Losartan caused a fall in baseline systemic vascular resistance. Despite the similar mean arterial pressure, the rise in systemic vascular resistance after angiotensin II during D-glucose infusion (162 ng min−1 kg−1, 8065± 1967 dyn s cm−5) was reduced during losartan infusion (1458 ng min−1 kg−1, 6645 ±1720 dyn s cm−5. Losartan caused a small rise in cardiac output related to a rise in heart rate and increased stroke volume. Pressure infusions of angiotensin II caused a fall in cardiac output during D-glucose infusion, which was blocked during losartan infusion. The rise in heart rate in response to angiotensin II was similar during both D-glucose and losartan infusion, but with higher absolute values during losartan alone. There was a linear relationship between heart rate and the plasma concentration of angiotensin II, which was unaffected by losartan. Pulmonary pressure was marginally elevated by losartan, related to the rise in cardiac output, and was much less sensitive to angiotensin II infusion, rising only at the highest rate of infusion during both D-glucose and losartan infusion.
3. Losartan infusion alone caused a rise in plasma angiotensin II concentration with a fall in aldosterone concentration. During pressor infusions the measured angiotensin II concentrations suggested that losartan increased the clearance of angiotensin II. 4. Losartan has complex effects on cardiovascular function. The pressor response of mean arterial pressure to angiotensin II shows competitive inhibition, but this marks subtle effects on cardiac output and heart rate, in addition to systemic vascular resistance. In addition to elevating endogenous angiotensin II and suppressing aldosterone, losartan may enhance clearance of infused angiotensin II.