Showing papers in "Clinical Science in 1989"

A comparison of the visual analogue scale and modified Borg scale for the measurement of dyspnoea during exercise.

Abstract: 1. The intensity of breathlessness during exercise was measured in ten normal subjects using a visual analogue scale (VAS) and a Borg scale to compare the use of the scales and their repeatability, both within the duration of a period of exercise and between tests. For each scale, subjects performed two exercise tests separated by a period of 2-6 weeks. Each exercise test consisted of two cycles of progressively increasing and decreasing workload. 2. All subjects felt confidently able to use both scales to quantify their feelings of breathlessness exclusively of other sensation. Equal preference was expressed for use of a particular scale. 3. With both scales there was a large intersubject variation in the relationship between dyspnoea score and minute ventilation (VE) (P less than 0.01), and in the range of the scale used. 4. There was a good correlation between the VAS and Borg scores at each level of VE (r2 = 0.71), but the VAS score was used over a wider range than the Borg score. 5. The relationship between VE and the dyspnoea score measured by the two techniques was predominantly linear. The mean r2 for VAS score/VE was 0.68 (SD 0.19) and for Borg score/VE the mean r2 was 0.75 (SD 0.13). 6. The relationships VAS score/VE and Borg score/VE were unaffected by the direction in which the workload was varied (P greater than 0.05). 7. VE, measured at each work rate, did not differ between the two cycles (P greater than 0.05) or between the 2 days (P greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Possible connections between stress, diabetes, obesity, hypertension and altered lipoprotein metabolism that may result in atherosclerosis.

Abstract: This review has discussed some metabolic and endocrine changes that can be associated with a stress type of metabolism, diabetes, obesity, hypertension, smoking and the consumption of diets rich in fat and refined sugar, or poor in ascorbate. These are some of the risk factors associated with premature atherosclerosis, coronary thrombosis and stroke. It has been proposed that an increased control of metabolism by the 'stress' or counter-regulatory hormones, relative to insulin, is a common feature of these risk factors. Particular emphasis was placed upon the action of the glucocorticoids which can produce insulin insensitivity, leading to hyperglycaemia, hypertriglyceridaemia, hypercholesterolaemia and hyperinsulinaemia. Furthermore, glucocorticoids can decrease energy expenditure and, together with insulin, promote energy deposition. These observations provide a partial explanation for the metabolic changes that can accompany the risk factors and clarify why they interact in promoting atherosclerosis.

Lipoxin A4 and lipoxin B4 inhibit chemotactic responses of human neutrophils stimulated by leukotriene B4 and N-formyl-L-methionyl-L-leucyl-L-phenylalanine.

Abstract: 1. Lipoxin A 4 (LXA 4 ) and lipoxin B 4 (LXB 4 ) have been evaluated for their capacities to modulate neutrophil (PMN) migration and endothelial cell adherence using compounds prepared by total chemical synthesis. 2. Increased PMN migration was seen with concentrations of LXA 4 from 10 −9 mol/l to 10 −7 mol/l. LXA 4 was 100-fold less potent than leukotriene B 4 (LTB 4 ) and it elicited only one-half of the maximal response of LTB 4 . 3. The (5 S ,6 S ,15 S )-isomer of LXA 4 induced only a weak migratory response and LXB 4 was inactive, suggesting that the activity of LXA 4 was stereospecific. 4. Modified chequerboard analysis indicated that LXA 4 was a chemokinetic agent. 5. Preincubation of PMN with increasing concentrations of LXA 4 induced a very similar dose- and time-dependent inhibition of the subsequent response to 10 −7 mol/l LTB 4 or 10 −7 mol/l N -formyl-l-methionyl-l-leucyl-l-phenylalanine (FMLP). The inhibition was observed at 10 −10 mol/l LXA 4 ; the concentration which produced 50% inhibition was 10 −8 mol/l and 100% inhibition of PMN locomotion occurred at 10 −6 mol/l LXA 4 . 6. The (5 S ,6 S ,15 S )-isomers of LXA 4 and LXB 4 were 5- and 100-fold less potent than LXA 4 , respectively, in suppressing LTB 4 - or FMLP-induced PMN migration. 7. Preincubation of PMN with LXA 4 led to a suppression of calcium mobilization, as assessed by Quin2-AM fluorescence, when the cells were subsequently stimulated under optimal conditions by LTB 4 or FMLP. 8. These results suggest that the inhibitory activity of lipoxins may be related to the capacity of these molecules to regulate calcium ion mobilization. 9. LXA 4 and LXB 4 did not promote PMN adherence to human endothelial cell monolayers and they did not modulate FMLP-stimulated PMN-endothelial cell adhesion.

Increase in anterior tibialis muscle protein synthesis in healthy man during mixed amino acid infusion: studies of incorporation of [1-13C]leucine.

Abstract: 1. Anterior tibial muscle protein synthesis in seven healthy postabsorptive men was determined from increases in muscle protein bound leucine enrichment during a primed continuous infusion of L-[1-13C]leucine. Biopsies were taken 30 min after the beginning of leucine infusion (when plasma 13C enrichment was steady), 240 min later during continued fasting and again after 240 min of infusion of a mixed amino acid solution which increased plasma total amino acid concentrations by 37%. The mean enrichment of 13C in plasma alpha-ketoisocaproate was used as an index of the enrichment of the precursor pool for leucine metabolism. 2. Anterior tibial muscle mixed protein synthetic rate during fasting was 0.055 (SD 0.008)%/h and this increased by an average of 35% during infusion of mixed amino acid to 0.074 (SD 0.021)%/h (P less than 0.05). 3. Whole-body protein breakdown (expressed as the rate of endogenous leucine appearance in plasma) was 121 (SD 8) mumol h-1 kg-1 during fasting and decreased (P less than 0.01) by an average of 12% during amino acid infusion. Leucine oxidation was 18 (SD 3) mumol h-1 kg-1 during fasting and increased (P less than 0.001) by 89% during amino acid infusion. Whole-body protein synthesis (non-oxidative leucine disappearance) was 104 (SD 6) mumol h-1 kg-1 during fasting and rose by 13% (P less than 0.001) during mixed amino acid infusion. 4. 13C enrichment of muscle free leucine was only 61 (SD 19)% of that in plasma alpha-ketoisocaproate and this increased to 74 (SD 16)% (P less than 0.02) during mixed amino acid infusion. 5. The results suggest that increased availability of amino acids reverses whole-body protein balance from negative to positive and a major component of this is the increase in muscle protein synthesis.

Circadian rhythm of glomerular filtration rate in normal individuals

Abstract: 1. In a group of 11 normal individuals we measured glomerular filtration rate (GFR) by inulin clearances and effective renal plasma flow (ERPF) by p-aminohippurate clearances during a period of 24 h and a regimen of bedrest, identical food intake per 3 h and normal sleep/wake and light/dark cycles. 2. All subjects had a circadian rhythm for GFR with a maximum of 122 ml/min (SD 22) in the daytime, a minimum of 86 ml/min (SD 12) at night and with a relative amplitude of 33% (SD 15). 3. ERPF had a circadian rhythm with a similar relative amplitude as the GFR rhythm, but with a different phase. Because of this difference in phase, the calculated filtration fraction (GFR/ERPF) followed a circadian rhythm as well. 4. The circadian rhythms of urine volume and sodium excretion were in phase with the GFR rhythm, but the potassium rhythm had a different phase, probably because urinary potassium is largely derived from tubular secretion. 5. Urinary albumin and beta 2-microglobulin excretion had a circadian rhythm in phase with the GFR rhythm. 6. The highest quantity of sodium, water and beta 2-microglobulin was reabsorbed in the daytime; tubular reabsorption, expressed as percentage of the filtered load (fractional reabsorption), had a rhythm with a reversed phase.

The initial responses to cold-water immersion in man.

Abstract: This review is summarized in Fig. 1. It is concluded that the cold-shock response can result in the death or serious incapacitation of an individual long before general hypothermia develops. As such, this response is probably responsible for the majority of annual open-water immersion deaths.

Metabolic characteristics of human adipose tissue in vivo.

Abstract: 1. A method was developed for sampling the venous drainage from the subcutaneous adipose tissue of the anterior abdominal wall. This is a large depot in many subjects, and seems well suited to such studies as it is completely separated from the venous drainage of the underlying muscle by the aponeurosis of the external oblique muscle. 2. Eight normal subjects were studied after an overnight fast, and for 120 min after ingestion of 75 g of glucose. Concentrations of substrates in the abdominal wall drainage were compared with those in arterialized blood and in forearm muscle drainage. 3. Non-esterified fatty acid and glycerol concentrations in the abdominal wall drainage were high (three to four times the arterial level) after overnight fast. After glucose ingestion, arterial and abdominal venous levels fell and the arteriovenous differences narrowed. The forearm showed uptake of non-esterified fatty acids when fasting but not after glucose ingestion, with no significant arteriovenous difference for glycerol at any time. 4. The abdominal wall tissues showed a small arteriovenous difference for glucose uptake during fasting, which increased after glucose ingestion. Although lactate was produced throughout, its molar ratio to glucose uptake was less than that reported for other superficial sites, suggesting only a minor contribution of skin metabolism. Forearm muscle showed a larger and more prolonged increase in arteriovenous difference for glucose uptake after the glucose load, but no consistent release or uptake of lactate. 5. We conclude that the tissue studied by this technique is predominantly adipose. This technique may have wide application in studies of the metabolic basis for body weight regulation in man.

Muscle enzyme adaptation in patients with peripheral arterial insufficiency: spontaneous adaptation, effect of different treatments and consequences on walking performance.

Abstract: 1. The activities of phosphofructokinase (PFK), citrate synthetase (CS), lactate dehydrogenase (LDH), 3-hydroxyacyl-CoA dehydrogenase (ACDH) and cytochrome- c oxidase (Cyt-ox) in the calf muscle tissue were compared in subjects with intermittent claudication ( n = 38) and controls ( n = 20). The activities of CS, ACDH and Cyt-ox were increased and the activity of Cyt-ox was positively correlated to the maximal walking distance (MWD) in the patients. 2. Thirty-three patients with intermittent claudication were randomized to three treatment groups: (1) operative surgery, (2) operative surgery supplemented with physical training and (3) physical training alone. Before and after 6–12 months of treatment, symptom-free walking distance (SFWD), MWD, ankle-brachial blood pressure quotient (ankle index), maximal plethysmographic calf blood flow (MPBF) and the activities of PFK, CS, LDH, ACDH and Cyt-ox were measured. 3. SFWD and MWD increased in all three groups. Ankle index and MPBF increased in groups 1 and 2, but were unchanged in group 3. The activities of Cyt-ox and CS decreased with operation, but the activity of Cyt-ox was further augmented with training in group 3. Overall, the change in ankle index explained 80–90% of the variability in walking performance. In a separate analysis, the increased activity of Cyt-ox in group 3 was positively correlated to, and explained 31% of the variability in, the improvement in SFWD. 4. These findings indicate that both physical activity and a reduced calf blood flow are necessary conditions for the enzymatic adaptation to take place. A causal relationship betweeen metabolic adaptation in the muscle tissue and walking performance is suggested. The possible importance of other factors as determinants of walking ability is also discussed.

Measurement of the rate of protein synthesis in muscle of postabsorptive young men by injection of a 'flooding dose' of [1-13C]leucine.

Abstract: 1. The 'flooding dose' technique for measuring the rate of protein synthesis in tissues in vivo involves the injection of a large amount of unlabelled amino acid together with the tracer to minimize differences in isotopic enrichment of the free amino acid in plasma and tissue compartments. This approach has been investigated in human muscle by taking biopsies from postabsorptive male volunteers given [1-13C]leucine. 2. Intravenous injection of 4 g of unlabelled leucine resulted in a rapid rise in free leucine concentration of seven- to eleven-fold in plasma and five-fold in muscle. Values were still elevated by two-fold after 2 h. 3. Five minutes after injection of [1-13C]leucine (0.05 g/kg) the isotopic enrichment of plasma leucine was 82% that of the injected material, falling to 44% at 120 min. The enrichment of free leucine in sequential muscle biopsies was close to that in plasma and almost identical to that for plasma alpha-ketoisocaproate. 4. The rate of protein synthesis was determined from the increase in leucine enrichment in protein of muscle biopsies taken before and 90 min after injection of [1-13C]leucine (0.05 g/kg; 19 or 39 atom% excess) and the average plasma alpha-ketoisocaproate enrichment over this period (taken to represent muscle free leucine). The mean rate of muscle protein synthesis in 10 subjects was 1.95 (SEM 0.12) %/day. Rates of protein synthesis calculated from plasma leucine as precursor enrichment were only 5% lower than those calculated from plasma alpha-ketoisocaproate.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial natriuretic peptide release during sleep in patients with obstructive sleep apnoea before and during treatment with nasal continuous positive airway pressure.

Abstract: 1. Plasma levels of atrial natriuretic peptide (ANP) were measured in seven patients with obstructive sleep apnoea (OSA) while they were awake, during repetitive apnoea and during treatment with nasal continuous positive airway pressure (CPAP). 2. ANP levels in both pulmonary artery and peripheral venous samples were elevated during apnoeic sleep and reduced when apnoea was prevented by nasal CPAP. Mean values of pulmonary artery ANP were 116.3 +/- 17.9 pg/ml during apnoea and 64.8 +/- 15.2 pg/ml (P less than 0.05) on nasal CPAP. 3. It is concluded that there is increased ANP release during sleep in patients with OSA and that CPAP treatment normalizes ANP secretion. These findings may explain previously identified urinary abnormalities in OSA.

Altered platelet function during mental stress and adrenaline infusion in humans: evidence for an increased aggregability in vivo as measured by filtragometry.

Abstract: 1 The effects of mental stress induced by a colour word conflict test (CWT; n = 9) or 3 h infusions of placebo or adrenaline (04 nmol min-1 kg-1; n = 9) on platelet function in vivo were studied in 16 healthy male volunteers 2 Platelet function was assessed by a filtragometry technique, which reflects aggregability in vivo, and by measurements of the plasma levels of beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4) 3 Adrenaline and CWT induced marked cardiovascular responses as expected Venous plasma adrenaline increased from 01-02 nmol/l at rest to 487 +/- 042 nmol/l during adrenaline infusion and to 046 +/- 010 nmol/l during CWT 4 Filtragometry measurements were reproducible within individuals with coefficients of variation of 79% during placebo infusion and 54% for resting measurements between days 5 Platelet aggregability, as measured by filtragometry, was similarly increased during both adrenaline infusion (P less than 005) and CWT (P less than 001) 6 The coefficients of variation for beta-TG and PF4 levels were 173% for log beta-TG and 279% for log PF4 between days, but could not be calculated for within-day variability Both beta-TG (P less than 005) and PF4 (P less than 001) levels decreased time-dependently during placebo infusion, indicating that long resting periods (hours) are needed to attain basal levels Artefactual results could not be identified by evaluating beta TG/PF4 ratios 7 beta-TG and PF4 levels did not decrease time-dependently during adrenaline infusion There were no significant changes of beta-TG or PF4 during CWT(ABSTRACT TRUNCATED AT 250 WORDS)

Capillary permeability and extracellular fluid volumes in pregnancy-induced hypertension.

Abstract: 1. Capillary permeability was determined by the disappearance rate of Evans Blue dye from plasma in healthy non-pregnant women, normal third-trimester primigravidae and primigravidae with pregnancy-induced hypertension. 2. Extracellular fluid volume was determined from the disappearance curves of injected mannitol in the same subjects and the plasma volume was measured by the Evans Blue dye dilution technique. 3. In normal pregnancy capillary permeability was not altered from that of non-pregnant subjects. Although extracellular fluid volume and plasma volume were increased in normal pregnant compared with non-pregnant women, the distribution of fluid between plasma volume and interstitial fluid volume was unaltered. 4. Women with established pregnancy-induced hypertension had a more rapid Evans Blue disappearance rate and a lower plasma volume than normal pregnant women, independent of the presence of proteinuria. Maternal plasma volume correlated positively and significantly with fetal birth weight in women with pregnancy-induced hypertension, emphasizing the important relationship between maternal plasma volume and fetal outcome. 5. The increased capillary permeability in women with pregnancy-induced hypertension was associated with a reduction in the plasma volume/interstitial fluid volume ratio but a normal extracellular fluid volume, suggesting that the reduced plasma volume did not result from sodium loss but rather from a redistribution of the total extracellular fluid volume. These changes did not differ significantly in subgroups with and without oedema.

Cardiac autonomic dysfunction in obese subjects

Abstract: 1. The prevalence of cardiac autonomic alterations was evaluated in 23 obese subjects with body mass index 37.2 +/- 3.03 kg/m2 (mean +/- SD), compared with 78 controls with body mass index 22.5 +/- 2.6 kg/m2 (P less than 0.001). 2. Cardiac autonomic function was assessed by four standard tests (heart rate response to deep breathing and to the Valsalva manoeuvre, systolic blood pressure fall after standing and diastolic pressure rise during handgrip) and by the cross-correlation test, a new method of computerized analysis of respiratory sinus arrhythmia based on spectral analysis of electrocardiographic and respiratory signal. 3. Considering tests indicative of parasympathetic function, only the heart rate response to the deep breathing and the cross-correlation test were significantly lower in the obese than in the control group [deep breathing = 13.95 +/- 8.65 beats/min (mean +/- SD) vs 24.5 +/- 7.65, P less than 0.001; cross-correlation 4.28 +/- 0.74 units vs 5.14 +/- 0.63, P less than 0.001]. Deep breathing and/or cross-correlation were abnormal in 10 (43.5%) obese subjects (deep breathing: seven subjects, cross-correlation: eight subjects). No significant difference between groups was found for the response to the Valsalva manoeuvre: the Valsalva ratio was 1.69 +/- 0.45 in obese subjects and 1.88 +/- 0.33 in controls (P = NS). The Valsalva ratio was abnormal in three obese subjects. 4. No significant differences were found between groups for tests indicative of sympathetic function.(ABSTRACT TRUNCATED AT 250 WORDS)

Ascorbic acid: a factor concentrated in human gastric juice.

Abstract: 1. Concentrations of ascorbic acid (ascorbic and dehydro-ascorbic; A+D; measured by the 2,4-dinitrophenylhydrazine method) of nearly three times those of plasma are present in gastric juice samples from patients with normal gastric histology. 2. A significant reduction in gastric juice ascorbic acid (A+D) was observed in patients with chronic gastritis. This reduction in concentration was independent of the grade of gastritis. 3. Concentrations of ascorbic acid (A+D) in gastric biopsy specimens were consistently higher in the antrum than in the body of the stomach. 4. These data demonstrate that considerable quantities of ascorbic acid (A+D) are normally ‘secreted’ into the stomach. 5. Ascorbic acid (ascorbic only; A; measured by h.p.l.c.) was present predominantly in its biologically active form in the patients with normal gastric histology. However, in patients with gastritis, independent of grade, ascorbic acid was present predominantly in its oxidized, biologically inactive form.

Effects of insulin on human adipose tissue metabolism in vivo.

Abstract: 1. The metabolic effects of insulin on human adipose tissue were studied by combining the euglycaemic clamp technique with measurement of arteriovenous differences across the subcutaneous adipose tissue of the anterior abdominal wall. 2. Eight normal subjects were studied after an overnight fast, and for 120 min during infusion of insulin (mean arterialized plasma insulin 50-55 m-units/l). 3. During the insulin infusion, the arterialized and abdominal venous levels of both non-esterified fatty acids and glycerol fell, and the arteriovenous differences for the release of these substances narrowed. The fractional rate of re-esterification of fatty acids was around 20% in the fasting state and increased to almost 100% during hyperinsulinaemia. 4. In the fasting state the uptake of glucose and 3-hydroxybutyrate by adipose tissue could account for only 20% of the oxygen uptake. During insulin infusion, adipose tissue glucose uptake increased and could account for more than 100% of oxygen uptake, implying storage of glucose. 5. Net balances of different substrates across adipose tissue were examined by calculating fluxes in terms of microgram-atoms of carbon. In the fasting state adipose tissue was in marked negative carbon balance (because of the export of non-esterified fatty acids); during insulin infusion it just reached 'carbon balance'. These results were in contrast to those from a previous study of glucose ingestion, in which the adipose tissue showed marked positive carbon balance (net substrate deposition).

Urinary albumin excretion and blood pressure in the general population.

Abstract: 1. Twenty-four hour urinary albumin excretion rate was measured by a sensitive radioimmunoassay in 99 male and 100 female randomly selected factory workers, aged between 20 and 60 years. 2. The median (range) albumin excretion rates for men and women of 4.67 (1.0-25.8) and 5.25 (0.2-33.0) mg/24 h, respectively, were not significantly different. 3. No correlation was established between diastolic, systolic or mean arterial blood pressure and albumin excretion rate for the whole group. 4. Twenty-eight subjects with systolic and/or diastolic blood pressures greater than or equal to 140/90 mmHg (18.7/12.0 kPa) showed a positive correlation between mean arterial blood pressure and albumin excretion rate (r = 0.412, P less than 0.01). 5. There was no significant relationship between number of cigarettes smoked, age or alcohol intake and albumin excretion rate. 6. The data suggest that in the general population albumin excretion rate is variable and not dependent on blood pressure, but at blood pressures greater than 140/90 mmHg (18.7/12.0 kPa) albumin excretion rate may become pressure dependent, although high albumin excretion rates were sometimes found in subjects with blood pressures less than 140/90 mmHg (18.7/12.0 kPa).

Effects of meal composition on the postprandial blood pressure, catecholamine and insulin changes in elderly subjects.

Abstract: 1. The effects of four meals of similar energy, but different nutritional, composition on postprandial blood pressure, heart rate, autonomic function, catecholamines, insulin and packed cell volume levels were studied in seven fit elderly subjects. 2. The high carbohydrate and high protein meals led to a significant overall fall in supine systolic and diastolic blood pressure compared either with no change or a rise after the normal (i.e. mixed) and high fat meals. Similar between-meal differences were seen with erect diastolic but not erect systolic blood pressure. No significant postural blood pressure fall occurred after any of the meals. Supine heart rate was unaffected by meal type or by time, and although erect heart rate showed a small increase during the study there was no between-meal difference. 3. Parasympathetic function was unaffected by meal type. Plasma noradrenaline rose after the high carbohydrate and mixed meals only, remaining elevated for 120 min after meal consumption. This increase was not related to the changes in blood pressure or plasma insulin levels. 4. Plasma insulin and glucose rose after the high carbohydrate and mixed meals, but were unchanged after the high protein and high fat meals. Packed cell volume showed a small decrease towards the end of the study, although there was no between-meal variation. 5. The differences in the cardiovascular changes after the different meals could not be ascribed to alterations in autonomic function, insulin release or fall in plasma volume. We propose that the postprandial changes in blood pressure are due to the nutrient composition of the meal rather than the actual energy load.

Reduced selenium status of patients with asthma.

Abstract: 1. Selenium is an essential component of glutathione peroxidase (GSH-Px, EC 1.11.1.9), an enzyme which helps protect cells against damage caused by free radicals and hydroperoxides. 2. We report the plasma, whole blood and platelet concentrations of selenium, and whole blood and platelet activities of GSH-Px, in 49 patients with asthma, 23 of whom had coexisting eczema, and 76 healthy control subjects. 3. The asthmatic patients had significantly lower concentrations of selenium measured in plasma ( P P 4. No overall decrease in platelet or whole blood GSH-Px activity was found when the asthmatic and control groups were compared. 5. Although patients with symptomatic asthma have a reduced selenium status, this does not appear to influence the antioxidant capacity of their circulating blood cells.

Transamination of methionine in humans

Abstract: 1. This study was designed to investigate the transamination pathway of methionine in humans. 2. Evidence is provided that methanethiol and its metabolites are formed via transamination of methionine. 3. Gas-liquid chromatography was used to measure serum and urinary transamination metabolites of methionine: 2-keto-4-methylthiobutyrate, 3-methylthiopropionate and methanethiol, and the metabolites of methanethiol, dimethylsulphide, protein—S—S—CH3 (a mixed disulphide of blood proteins and methanethiol) and X—S—S—CH3 (a mixed disulphide of methanethiol and another thiol with an unknown component X). 4. Methionine and the transamination intermediates were measured in 10 normal subjects, in six normal subjects after L-methionine loading (0.1 g/kg body weight) and in a male patient with hepatic methionine adenosyltransferase (EC 2.5.1.6) deficiency. 5. In the patient with methionine adenosyltransferase deficiency, at least 20% of methionine was degraded via transamination. In normal subjects transamination of methionine did exist but was quantitatively not important in methionine catabolism, not even after methionine loading. 6. The results of this study might be of importance for future studies on the role of methanethiol in hepatic encephalopathy.

Whole body protein turnover and resting metabolic rate in homozygous sickle cell disease.

Abstract: 1. Whole body protein turnover and resting metabolic rate were measured in six adults with homozygous sickle cell disease (genotype HbSS) and in six normal adults (genotype HbAA) of similar age. 2. Turnover was measured with prime/intermittent oral doses of [15N]glycine over 18 h and resting energy expenditure was measured by indirect calorimetry. 3. In HbSS, nitrogen flux (0.9 +/- 0.08 g day-1), protein synthesis (6.0 +/- 0.5 g day-1 kg-1) and protein degradation (5.6 +/- 0.5 g day-1 kg-1) were significantly increased compared with HbAA nitrogen (flux 0.5 +/- 0.02 g day-1 kg-1, protein synthesis 3.2 +/- 0.2 g day-1 kg-1 and protein degradation 2.8 +/- 0.2 g day-1 kg-1). 4. Resting energy expenditure was significantly higher in HbSS compared with HbAA when expressed per unit of body weight (115 +/- 3 and 94 +/- 4 kJ day-1 kg-1, respectively) or weight 0.75(317 +/- 6 and 269 +/- 8 kJ day-1 kg-0.75, respectively). 5. The increase in protein turnover and energy expenditure suggest that patients with HbSS exist in a hypermetabolic state that requires greater dietary energy compared with HbAA.

Pulmonary endothelium-derived relaxing factor is impaired in hypoxia.

Abstract: 1. The vasoconstrictor and vasodilator activity of cultured bovine pulmonary artery endothelial cells was measured to determine how exposure to different partial pressures of O2 [PO2 142,42 and 15 mmHg (18.9, 5.6 and 2 kPa)] affects the production of endothelial-derived relaxing and constrictor factors. 2. A de-endothelialized rat aortic ring [maintained at a PO2 of 142 mmHg (18.9 kPa)] was used to bioassay the effluent from a perfused column of bovine endothelial cells grown on microcarrier beads. The endothelial cells were stimulated by 10(-7) mol/l bradykinin given for 1 min at 12 min intervals. 3. At the start, middle and end of the experiment the bovine endothelial cells were exposed to a PO2 of 142 mmHg (18.9 kPa) and when stimulated by bradykinin the perfusate caused respectively a 70 +/- 4%, 63 +/- 6% and 63 +/- 6% (mean +/- SEM) relaxation of an aortic ring which had been pre-contracted by 10(-6) mol/l phenylephrine. At a PO2 of 42 mmHg (5.6 kPa) the relaxation induced by the cells was not significantly altered, but this tailed to zero after 26-38 min exposure of the cells to a PO2 of 15 mmHg (2 kPa). 4. These responses were unaltered by the presence of 10(-5) mol/l indomethacin, suggesting that prostacyclin is not a significant vasodilator in this system. 5. Reduced production of endothelium-derived relaxant factor rather than production of a constrictor factor, or a direct effect on the smooth muscle, may be involved in pulmonary hypoxic vasoconstriction.

Availability of amino acids supplied by constant intravenous infusion of synthetic dipeptides in healthy man.

Abstract: 1. A commercial amino acid solution supplemented with two synthetic dipeptides, L-alanyl-L-glutamine (Ala-Gln) and glycyl-L-tyrosine (Gly-Tyr), or alternatively with isonitrogenous amounts of free alanine and glycine has been continuously infused over 4 h in six apparently healthy volunteers. 2. The infusion of the solutions was not accompanied by any side effects and the volunteers reported no complaints. 3. Infusion of the alanine- and glycine-supplemented control solution resulted in an increase of the concentration of these amino acids, while no appreciable change in free glutamine concentration was observed and free tyrosine revealed a steady decrease throughout the infusion. 4. Infusion of the peptide-supplemented solution resulted in a prompt equimolar liberation of the constituent free amino acids (glutamine, alanine, tyrosine and glycine), approaching steady state after about 30 min infusion, while only trace but stable concentrations of the two dipeptides were measured throughout the infusion. No peptides were detectable in urine. The findings suggest a nearly quantitative extracellular hydrolysis of the infused dipeptides and indicate a subsequent utilization of the liberated free amino acids. 5. The estimated metabolic clearance rates and total body plasma clearances were very similar for the two dipeptides (Ala-Gln 35.9 +/- 9.5 ml min-1 kg-1 and 2.9 +/- 0.9 l/min, respectively; Gly-Tyr 33.7 +/- 9.5 ml min-1 kg-1 and 2.7 +/- 0.9 l/min, respectively); thus there is little difference in the metabolic handling of these dipeptides.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevention of glucose-induced hypotension by the somatostatin analogue octreotide (SMS 201-995) in chronic autonomic failure: haemodynamic and hormonal changes.

Abstract: 1. The haemodynamic and hormonal changes following glucose ingestion (1 g/kg) were determined before and after pretreatment with either placebo or the somatostatin analogue, octreotide (SMS 201-995, 50 μg sub-cutaneously), in seven patients with chronic autonomic failure 2. In the placebo phase, after glucose, there was a marked and prolonged fall in blood pressure with no change in cardiac index and peripheral blood flow. Plasma insulin and neurotensin levels increased, whereas glucagon, vasoactive intestinal polypeptide, noradrenaline and adrenaline levels were unchanged 3. Octreotide transiently raised blood pressure and prevented glucose-induced hypotension. There were no changes in cardiac index or peripheral blood flow. Plasma insulin and neurotensin levels did not rise. Plasma glucose levels increased more slowly but reached a similar level to the placebo phase 4. We conclude that in autonomic failure patients, glucose-induced hypotension was not accompanied by changes in cardiac index or peripheral blood flow, indicating a lack of compensation to probable splanchnic vasodilatation. The hypotension was prevented by the peptide release inhibitor, octreotide, with no change in cardiac index or in peripheral blood flow, suggesting an effect on the splanchnic vasculature, probably through inhibiting release of vasodilatatory pancreatic and gut peptides.

Urinary excretion of dihydroxyphenylalanine and dopamine during alterations of dietary salt intake in humans.

Abstract: 1. Urinary excretion of dopamine (DA) increases during dietary salt loading. The majority of urinary DA is derived from circulating dihydroxyphenylalanine (dopa). Whether the increase in urinary DA excretion during salt loading results from increased efficiency of uptake of dopa by proximal tubular cells of the kidney, facilitation of intracellular conversion of dopa to DA, or increased delivery of dopa to tubular uptake sites, has been unknown. 2. In 10 inpatient normal volunteers on a constant diet, daily excretion of dopa and DA was assessed during normal sodium intake (109 mmol/day) for 1 week, low sodium intake (9 mmol/day) for 1 week and high sodium intake (249 mmol/day) for 1 week. 3. Urinary DA excretion exceeded urinary dopa excretion by about tenfold, and the excretion of both DA and dopa increased by about twofold between the low and high salt diets, with similar proportionate changes. Plasma dopa was unchanged by dietary salt manipulation. 4. The results indicate that increases in urinary DA excretion during dietary salt loading can be accounted for by increased delivery of dopa to sites of uptake by proximal tubular cells. Since dopa is released into the bloodstream by sympathetic nerve endings and by the brain, and since interference with decarboxylation of dopa attenuates natriuretic responses, dopa may function indirectly as a neurohormone involved in homoeostatic regulation of sodium balance.

Plasma dihydroxyphenylglycol for estimation of noradrenaline neuronal re-uptake in the sympathetic nervous system in vivo.

Abstract: 1. Neuronal re-uptake is the primary means for terminating the actions of endogenously released noradrenaline. A portion of the recaptured noradrenaline is deaminated to form dihydroxyphenylglycol. The present report describes a technique using plasma dihydroxyphenylglycol for estimation of the rate of neuronal reuptake of endogenous noradrenaline in vivo. 2. Neuronal re-uptake of noradrenaline in the sympathetic nervous system of the rat was estimated from the effects of neuronal uptake blockade with desipramine on three variables: (i) the plasma clearance of intravenously infused 3H-labelled noradrenaline, (ii) the plasma concentration of endogenous dihydroxyphenylglycol, and (iii) the plasma concentration of 3H-labelled dihydroxyphenylglycol formed from infused 3H-labelled noradrenaline. 3. Desipramine decreased plasma dihydroxyphenylglycol by 36%, this representing the fraction of dihydroxyphenylglycol in plasma that was derived from recaptured noradrenaline. After desipramine, the decrease in the rate of neuronal uptake of 3H-labelled noradrenaline was 9.7 times that of the decrease in the plasma spillover of 3H-labelled dihydroxyphenylglycol. Since the appearances in plasma of dihydroxyphenylglycol from unlabelled and 3H-labelled noradrenaline were similar, the neuronal re-uptake of endogenous noradrenaline could be assumed to be 9.7 times as much as the plasma spillover of dihydroxyphenylglycol that was derived from recaptured noradrenaline (0.15 nmol min-1 kg-1). 4. The rate of neuronal re-uptake of endogenous noradrenaline was estimated to be 1.45 nmol min-1 kg-1, whereas the plasma spillover of noradrenaline was 0.127 nmol min-1 kg-1. Thus, only a small fraction (less than 9%) of the noradrenaline released into the synaptic cleft spills over into the circulation.

The E1 α and β Subunits of the Pyruvate Dehydrogenase Complex are M2‘d’ and M2‘e’ Autoantigens in Primary Biliary Cirrhosis

Abstract: 1. Sera from 76 patients with primary biliary cirrhosis (PBC) and 66 control subjects (53 with chronic liver disease and 13 healthy normal women) were immuno-blotted against purified E1 component of bovine pyruvate dehydrogenase complex (PDC) and bacterial PDC. 2. Thirty-one out of seventy-six (41%) sera from PBC patients showed a positive response to bovine E1 alpha, and five of these 31 (7% of total) reacted with bovine E1 beta. None of the control sera reacted with bovine E1 alpha or beta. 3. None of the PBC sera that recognized bovine E1 subunits reacted with bacterial PDC E1. 4. In the PBC patients there was no correlation between presence of antibodies to E1 alpha and beta subunits and histological stage of the disease. 5. Our data demonstrate that the E1 alpha and beta components of mammalian PDC are the M2'd' and 'e' mitochondrial autoantigens, respectively.

Cardiovascular reflex responses in patients with unexplained syncope.

Abstract: 1. This study was undertaken to determine whether, in a group of patients complaining of recurrent syncopal attacks but with no apparent cause, there was evidence of abnormal cardiovascular reflex control. 2. The steady-state responses of blood pressure, heart rate and cardiac output to head-up tilting were determined in 67 patients using entirely ‘non-invasive’ methods. In some patients we also studied the immediate response of pulse interval to carotid baroreceptor stimulation by neck suction. 3. Two of the patients developed vasovagal attacks during the 20 min test period of head-up tilting. Eighteen others showed postural hypotension, defined as a fall in blood pressure to outside the limits of two sds from the mean values of age-related control subjects. 4. Patients who showed postural hypotension had a mean fall in cardiac output significantly larger than that in age-related control subjects. Responses in the non-hypotensive patients did not differ significantly from controls. 5. Stimulation of carotid baroreceptors resulted in significantly smaller responses of pulse interval in the patients defined as having postural hypotension compared with the non-hypotensive patients and with the age-related control subjects. 6. In some of the patients who did not show postural hypotension during the standard test, the duration of tilt was prolonged for up to 1 h. Five out of 26 patients developed vasovagal attacks. All the vasovagal patients showed an initial tachycardia and the response of pulse interval to neck suction was significantly larger than in the controls. 7. This study has shown that simple non-invasive tests of cardiovascular reflex function can divide patients with poor orthostatic tolerance into two groups: those with evidence of small reflex responses, associated with abnormally large falls in cardiac output during tilting, and those with evidence of overactive reflexes associated with the tendency to develop vasovagal syncope.

Effects of an olive-oil-rich diet on erythrocyte membrane lipid composition and cation transport systems.

Abstract: 1. In this study we sought to test the possibility that an olive-oil-rich diet might influence the membrane lipid composition and cation transport mechanisms in erythrocytes. 2. To this end, 11 normotensive normolipidaemic healthy volunteers were given a standard relatively low fat diet (28% of total energy) for 3 weeks, followed by a high fat (38% of total energy), olive-oil (100 g/day)-enriched diet for the 3 subsequent weeks, in a metabolic ward. The two diets contained the same amount of cholesterol (400 mg), and the polyunsaturated fatty acid/saturated fatty acid ratio was similar and comparatively low (0.35 on the standard vs 0.36 on the olive oil diet). 3. At the end of the study the lipid composition of the erythrocyte membranes showed the following changes: the oleic acid content increased by 15.7% and the amount of saturated fatty acid decreased by 3.2%. The polyunsaturated fatty acid content tended to decrease, while the polyunsaturated fatty acid/saturated fatty acid ratio did not change significantly. The cholesterol/phospholipid molar ratio increased significantly by 7.8%, still remaining within the reference range. 4. At the same time, the mean values of the maximum rates of the cation fluxes mediated by the Na+ -K+ pump, and by Na+ -K+ co-transport rose significantly, while the maximal rate of Na+ -L+ countertransport showed a non-significant trend towards lower values. 5. Urinary excretion of Na+ and K+, body weight and blood pressure did not change significantly.

Chronobiological study of the relationship between dyspnoea and airway obstruction in symptomatic asthmatic subjects.

Abstract: 1. We performed a chronobiological study of the relationship between peak expiratory flow rate (PEFR) and magnitude of dyspnoea in 35 symptomatic asthmatic patients to determine how accurately asthmatic subjects assess spontaneous airway obstruction and whether this accuracy varies throughout the 24 h period and depends on characteristics of the subjects or asthma. 2. At 07.00, 11.00, 15.00, 19.00 and 23.00 hours on 8 consecutive days in their ordinary environment and under their usual drug regimen, the subjects first rated their dyspnoea with a visual analogue scale and immediately after recorded their PEFR. 3. The linear regression coefficients between dyspnoea score and PEFR for the 35 subjects were continuously distributed between -0.93 and +0.21, with most r values ranging from -0.9 to -0.5. The group median r values calculated at each time point showed that strongest correlation between dyspnoea score and PEFR occurred at 7 h. which coincided with the lowest PEFR values. 4. We chose r = -0.7 (r2 = 0.5) as a limit to distinguish good perceivers (-1 less than r less than or equal to -0.7) from bad perceivers of airway obstruction. These two populations differed only by a higher variability of both PEFR and dyspnoea score in good than in bad perceivers, but not for severity, duration or treatment of asthma, absolute value of dyspnoea score, age or sex. 5. Our study quantified an important intra- and between-subject variability in the accuracy of perception of spontaneous airway obstruction in asthmatic subjects which seems to be unrelated to most characteristics of asthma.