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Biomedical subjects

R J Barnes

Publications and source records attributed to R J Barnes.

At least 19 recordsLinked to original sources

Metabolic adaptations for desert survival in the Bedouin goat.

Energy conservation is a key adaptation for desert survival in the Bedouin goat. When food is scarce, metabolism is reduced and body weight can be maintained indefinitely on less than one-half of normal intake. We hypothesized that metabolism would be turned down during both rest and exercise, but it was not. It was low when animals rested and returned to normal during exercise. We expected catecholamines and thyroid hormones would modulate metabolism, but they did not. The reduction in metabolism preceded any change in thyroid hormone concentrations, and infusions of epinephrine did not restore reduced metabolism to normal levels. Finally, we expected the gut would be the major organ system involved in the metabolic reduction because less food is eaten, processed, and absorbed. Contrary to our expectations, we found that muscle is the primary organ system responsible for the reduction. It appears that the adaptations of the Bedouin goat for surviving on limited food supplies involve different organ systems and different modulators to reduce metabolism from those known for other mammals.

Adaptation, Physiological↗

Changes in fetal thyroid hormone levels in adrenalectomized fetal sheep following continuous cortisol infusion 72 h before delivery.

Continuous infusion of cortisol into adrenalectomized fetal sheep during the last 72 h of gestation (term = 145 +/- 2 days) produced a significant (P < 0.05) rise in fetal serum tri-iodothyronine (T3) mean +/- S.E.M. concentrations from 398 +/- 65 to 1340 +/- 238 ng/l. A concurrent decrease in plasma thyroxine (T4) levels was observed in three out of four animals. No significant changes in the concentrations of either hormone were noted prior to the start of cortisol infusion. The plasma concentrations of cortisol, T3 and T4 at term were similar to those in untreated full-term lambs. Adrenalectomized fetuses not given cortisol infusions still had low levels of T3 at term, with no increase being observed. The results suggest that cortisol plays an important role in the increase of fetal plasma T3 observed towards the end of gestation. This is probably achieved by the stimulation of the monodeiodination of T4 to T3 in the peripheral tissues.

Adrenalectomy↗

A modified helium dilution technique for measuring small lung gas volumes.

The present study was undertaken to devise an accurate method for measuring functional residual capacity, FRC, in small and lively newborn animals such as lambs and piglets under flexible laboratory conditions using relatively simple equipment. This was achieved by adapting the standard helium dilution method so that FRC could be calculated from the helium equilibration concentration reached when the subject, having breathed a gas mixture with a high helium concentration, rebreathed from an air-filled spirometer. Using this technique, typical results for test volumes of 10, 20, 30 and 40 ml were measured as 10.7 +/- 0.34, 20.2 +/- 0.19, 30.5 +/- 0.40 and 40.6 +/- 0.75 ml respectively with corresponding coefficients of variation of 6.4%, 1.9%, 2.6% and 3.7%. Repeat measurements made on each of 3 urethane anaesthetised rabbits gave values for FRC of 45.64 +/- 0.9 ml (5 measurements), 37.22 +/- 0.8 ml (8 measurements) and 48.95 +/- 0.99 ml (8 measurements) confirming the reproducibility of results from animal preparations. The FRC of newborn lambs (12 animals) was 81.4 +/- 9.2 ml. The technique also allowed clear recordings of respiratory pattern essential to the analysis of variations in FRC.

Animals↗

Blood flow to and the metabolism of glucose and lactate by the liver in vivo in fetal, newborn and adult sheep.

1. The blood flow to the liver in fetuses near to term, in newborn and in adult sheep was measured in vivo by the Fick principle using radionuclide-labelled plastic microspheres and timed withdrawal of reference organ blood samples. 2. There is a rapid flow of blood, 410.1 +/- 41.8 ml min-1 (100 g liver)-1, mean +/- S.E.M., to the liver in the fetus. Immediately after birth the blood flow is significantly less (172.5 +/- 27.5 ml min-1 (100 g liver)-1), reflecting the loss of the umbilical venous return to the liver following delivery and separation from the placenta. Arterial blood flow to the liver per unit weight of liver was small in the fetus (9.5 +/- 1.2 ml min-1 (100 g liver)-1), significantly greater in the immediate newborn (27.9 +/- 7.9 ml min-1 (100 g)-1) but appeared to decline with age after birth to 12.2 +/- 6.6 ml min-1 (100 g)-1 in lambs at 16 weeks of age. Portal blood flow to the liver, on a weight basis, changed little with age being 126 +/- 20.9 ml min-1 (100 g liver)-1 in the fetus, 144.7 +/- 21.1 ml min-1 (100 g liver)-1 in the immediate newborn and 203.2 +/- 27.8 ml min-1 (100 g liver)-1 in the adult. 3. Oxygen consumption and glucose and lactate fluxes across the sheep liver were determined from 132 days of gestation into adulthood. 4. The oxygen consumption by the fetal liver was 0.11 +/- 0.02 mmol min-1 (100 g)-1 which represents about 6% of the total fetal oxygen metabolism. Immediately after birth there was an apparent increase in liver oxygen consumption but the wide variation in the values recorded means that the change is not statistically significant. There were no significant changes in liver oxygen consumption with age after delivery, oxygen consumption by the adult liver was 0.16 +/- 0.05 mmol min-1 (100 g)-1. 5. The liver at all ages studied consumed lactate. Lactate consumption was particularly high in the fetus (0.13 +/- 0.04 mmol min-1 (100 g)-1 and could account for three times the oxygen consumed by the fetal liver, but the fate of this lactate is not yet known. 6. In the fetus the liver is in approximately zero glucose balance; in contrast postnatal animals release glucose from the liver at rest.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗

Release of glucose from the liver of fetal and postnatal sheep by portal vein infusion of catecholamines or glucagon.

1. The blood flow to the liver in fetuses near term, newborn and adult sheep was measured by the Fick principle, using radionuclide-labelled plastic microspheres, before and during infusion of adrenaline, noradrenaline or glucagon. 2. Glucose output and lactate consumption by the liver in sheep of each age group were calculated by application of the Fick principle using the concentration gradients of these metabolites measured in blood samples obtained, simultaneously with blood flow measurements, from catheters chronically implanted in the inflow and outflow vessels of the liver. 3. Catecholamines were infused into the portal vein of fetuses near term at a rate comparable with that at which they are known to be secreted in the sheep fetus during moderate to severe hypoxia. The cardiovascular and metabolic responses to these infusions were found to be comparable with those that occur in the fetus during hypoxia. 4. Catecholamines increased glucose output from the liver in all except the immediate post-partum animals. Catecholamines were less effective than glucagon in promoting glucose release. The mean increments in glucose output during adrenaline infusion were 0.055 +/- 0.015 mmol min-1 (100 g liver)-1 in the fetus, 0.122 +/- 0.024 mmol min-1 (100 g)-1 in the 2-week-old lambs, 0.078 +/- 0.019 mmol min-1 (100 g)-1 in young lambs and 0.049 +/- 0.012 mmol min-1 (100 g)-1 in the adult sheep. During glucagon infusion the mean glucose output increments were 0.146 +/- 0.023 mmol min-1 (100 g)-1 in the fetus, 0.274 +/- 0.085 mmol min-1 (100 g)-1 in the 2-week-old and young lambs and 0.180 +/- 0.054 mmol min-1 (100 g)-1 in the adult. Adrenaline was more potent than noradrenaline, suggesting that the major glycogenolytic response might be beta-receptor mediated. 5. In the immediate newborn period the output of glucose from the liver was high (0.20 +/- 0.05 mmol min-1 (100 g liver)-1 and was not statistically significantly increased by infusion either of glucagon or of catecholamines which resulted in similar increments of glucose output of about 0.128 +/- 0.133 mmol min-1 (100 g)-1. It is probable that the high output of glucose reflected the high endogenous circulating levels of catecholamines and glucagon in these animals at birth and that further infusions failed to add significantly to the already near-maximal glucose release.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗

Long-term follow up of patients with gastritis associated with Helicobacter pylori infection.

The aim of this study was to evaluate the long-term prognosis for patients suffering from gastritis associated with Helicobacter pylori infection, and in particular the proportion of cases progressing to peptic ulcer. The study was carried out in one urban general practice. One hundred and three patients who had presented with dyspepsia over the 1973-80 period and who were found to have a macroscopically normal endoscopy were reassessed between seven and 14 years later. Gastric antral biopsies had been taken routinely at endoscopy and were subsequently re-examined for the presence of H pylori. The patients' medical records were examined to establish their consulting rates over the follow-up period and whether they suffered from any other medical conditions. Patients were interviewed to assess the course of their dyspeptic symptoms. Comparison of patients who were unequivocally H pylori positive with those who were negative revealed no significant differences in the consultation rate for gastroenterological symptoms, in the proportion of patients referred to a hospital consultant or for further gastroenterological investigations or in the proportion reporting that their symptoms had improved. However, a statistically highly significant relationship was found between H pylori infection and hypertension. The results of this study have shown that there is a good prognosis for non-ulcer dyspepsia whether or not H pylori infection is present. The association between H pylori gastritis and hypertension clearly merits further investigation.

Evaluation Studies as Topic↗

Preferential oxygen supply to the brain and upper body in the fetal pig.

In the fetal pig over 50% of the oxgenated umbilical venous blood bypasses the liver via vascular channels of over 100mu diameter which appear to act as a ductus venosus (DV). In the present experiments the oxygen levels (pO2, SO2 and O2 content) in the fetal carotid (CA) and femoral (FA) arteries were measured to determine whether preferential streaming of the oxygenated blood is maintained from the bypass to the foramen ovale and thence through the left heart to the upper body, as in other species. The results were obtained from 12 piglets catheterized and maintained in utero under sodium pentobarbitone anaesthesia. Significant CA-FA differences in pO2, SO2 and O2 content were observed in these fetuses during both normoxaemia and hypoxaemia showing that a higher level of oxygen can be maintained to the fetal head and brain over a wide range of oxygenation. These results confirm that the hepatic channels in the fetal piglet act as a fully functional DV.

Animals↗

Haemodynamic responses to stimulation of the splanchnic and cardiac sympathetic nerves in the anaesthetized cat.

The changes in cardiac output and mean right atrial pressure (R.A.P.) evoked at different circulating blood volumes by stimulation of the splanchnic sympathetic nerves were investigated in adrenalectomized cats under chloralose anaesthesia, with unopened chests and spontaneous respiration and with active vascular reflexes. The cardiac autonomic nerves were cut or blocked pharmacologically. Stimulation of the distal ends of the splanchnic nerves at 4 Hz caused aortic pressure and R.A.P. to rise to maximum values at 2 min before declining slowly. Cardiac output rose more slowly to a steady state at 3 min; at higher circulating volumes it fell initially. Although the output increments were slower in development they were better sustained than those in total peripheral resistance. The proportionate output increments were largest and the R.A.P. increments least at low circulating volumes whereas at high volumes the R.A.P. increments were large but the output changes were small or negative; the pattern of changes resembled that resulting from infusion of blood. Stimulation of the cardiac sympathetic nerves evoked a rise in output and a fall in R.A.P. related in magnitude to the initial value of R.A.P. On simultaneous stimulation of the splanchnic and cardiac sympathetic nerves the changes in output combined whereas the R.A.P. changes cancelled, to give output increments of 25-50% with little change in R.A.P. at all circulating volumes. At high circulating volumes infusion of blood did not usually alter output or aortic pressure, but splanchnic nerve stimulation increased peripheral resistance and aortic pressure and commonly evoked a rise in left ventricular stroke work which could not be accounted for by known adrenergic mechanisms or by elevation of left ventricular end-diastolic pressure. Portal venous pressure was consistently elevated by splanchnic nerve stimulation; it rose more slowly than did aortic pressure or R.A.P. and was independent of a changing central venous pressure provided this did not exceed +5 mmHg. The cardiac output increments were not related to changes in the ratio between the input and output resistances of the portal vein and it is concluded that displacement blood from the peripheral to the central vasculature was induced by contraction capacitance vessels.

Adrenalectomy↗

Changes in the blood flow to the digestive organs of sheep induced by feeding.

The blood flow to the digestive organs of nine sheep was determined by the use of isotopically labelled microspheres before, during and at 2 h and 4 h after feeding. Within 3 min of the start of feeding, the blood flow to the salivary glands and to the smooth muscle of the rumen and reticulum increased three-fold. The blood flow to the epithelium of the rumen and reticulum also increased before any appreciable effect on ruminal fermentation could have occurred. This increase in flow was greater in absolute but smaller in relative terms than that to the muscle. At 2 h after feeding blood flow to the epithelium of the rumen and reticulum was two to four times greater than before food was taken, while the flow to the smooth muscle of these organs had fallen to the level found before feeding. In the more distal parts of the gastrointestinal tract, blood flow changes in response to feeding were less pronounced and, where they occurred at all, consisted of decreases at different times. Thus blood flow to the omasum decreased during feeding but recovered thereafter, while the flows to abomasum, duodenum and ileum were not changed during feeding but were significantly lower at 2 h and 4 h later. In the rest of the small intestine and in the large intestine there were no significant changes in flow during the period of observation, nor were there any changes in the blood flow to pancreas or spleen. However, the flow to the omental and mesenteric fat declined abruptly on feeding and reached its minimal value 2 h afterwards. These results are in marked contrast to those reported in other species in that the subepithelial capillary plexus of the reticulum and rumen was the only region contributing to the increased hepatic portal blood flow after feeding.

Animals↗

Endoscopic studies of dyspepsia in a general practice.

In an urban general practice serving 7800 patients, all patients presenting over five and a half years with dyspepsia lasting more than two weeks were investigated by fibreoptic endoscopy and cholecystography, and many by barium meal. Of the 393 patients with dyspepsia, 346 completed the investigation: 180 had specific disease of the oesophagus, stomach, duodenum, or gall bladder, including six with carcinoma. Al further 67 had mucosal disease, and only 99 patients had no abnormality. After the first year the number of patients presenting annually and the percentage of patients with specific lesions remained constant. The annual incidence for patients with dyspepsia was about 1% and for patients with specific lesions 0.4%, suggesting that each year those who became symptom free (either spontaneously or because of treatment) were balanced by a similar number who developed symptoms. In contrast to the conclusions of other workers that an "open-access" endoscopy service could not be justified because the number of patients with specific lesins fell during their survey, we suggest that such endoscopy services are indeed worth while for providing an accurate diagnosis of dyspepsia.

Cholecystography↗

Haemodynamic responses to stimulation of the cardiac autonomic nerves in the anaesthetized cat with closed chest.

1. The changes in cardiac output and mean right atrial pressure (R.A.P.) evoked by stimulation of the cardiac autonomic nerves were investigated in cats under chloralose anaesthesia, with unopened chests and spontaneous respiration, and with active vascular reflexes. Cardiac output was measured by thermal dilution; the technique used was calibrated against the direct Fick method.2. The initial values of R.A.P. and output were varied by infusion of dextran-saline solution followed by withdrawal of blood. At positive values of R.A.P. withdrawal of blood caused a fall in R.A.P. with no change in cardiac output. At negative R.A.P. blood withdrawal caused a fall in output with little change in R.A.P.: the linear regression coefficient for output on R.A.P. was 48.2 ml./min.kg.mmHg (S.E. 2.06, n = 63, nine cats).3. Stimulation of the right cardiac sympathetic nerve increased heart rate by 69.2 beats/min (S.E. 4.0) from the resting rate of 158 beats/min (S.E. 6.3, ten cats). The acceleration was accompanied in most instances by a rise in cardiac output and a fall in R.A.P. and the magnitude of the rise in output was related to that of the fall in R.A.P.4. In no experiment could R.A.P. be reduced below -2.5 mmHg either by withdrawal of blood or by sympathetic stimulation. At negative values of R.A.P. the fall in R.A.P. and rise in output evoked by sympathetic stimulation were small; substantial changes could be obtained only from positive initial values of R.A.P. The proportional increase in output evoked by a given proportional increase in heart rate during near-maximal sympathetic stimulation had a linear relationship to the initial value of R.A.P. over the range -2 to +8 mmHg. The output increment was less than proportional to the rate increment at all values of R.A.P. below +3 mmHg.5. In five experiments stimulation of the left cardiac sympathetic nerve evoked a greater increase in output for a given increase in heart rate than did stimulation of the right nerve; on the other hand both nerves gave similar increments of output for a given fall in R.A.P.6. Stimulation of the distal end of the right vagus nerve slowed the heart and caused a fall in cardiac output and a rise in R.A.P. The change in output associated with a given change in R.A.P. was significantly greater (P = 0.05) during sympathetic than during vagal stimulation in 14 out of 18 tests; the difference increased as circulating volume was reduced.7. It is concluded that the relationship between cardiac output and R.A.P. during sympathetic and vagal stimulation is consistent with the hypothesis that neurally evoked changes in cardiac performance vary output mainly, but not exclusively, by inducing changes in R.A.P. which alter the pressure gradient for the return of blood to the right atrium from the periphery.

Animals↗

Pancreatic beta-cell function in the fetal foal and mare.

Insulin secretion and the factors influencing beta-cell function were investigated in the chronically catheterized fetal foal and mare during the second half of gestation. The response of the fetal beta cells to exogenous glucose was also examined. The mean concentration of insulin in the fetal foal was 7.5 +/- 0.5 (S.E.M.) microunit./ml (n = 20) which was significantly less than the corresponding maternal value of 49.0 +/- 5.0 microunit./ml (n = 20, P < 0.01). The insulin concentration in non-pregnant horses was 24.5 +/- 1.5 microunit./ml (n = 5) which was significantly less than the value in the pregnant animals (P < 0.01). However, there was no significant difference in the mean glucose concentration between the groups of adult animals. The insulin concentration was related to the endogenous glucose level in both adult and fetal horses. Wide variation in the maternal insulin concentration was observed above a glucose concentration of about 5.0 mmol/l. The mean concentration of insulin in pregnant mares decreased with increasing gestational age while the mean glucose concentration remained unaltered throughout the second half of gestation. There was no change in the basal concentrations of insulin or glucose in the fetus with gestational age although the fetal beta-cell response to exogenous glucose appeared to increase with increasing fetal age after 270 days of gestation (term 330 days). There was a significant arterio-venous difference in the concentration of insulin across the gravid uterus in the mare when the arterial insulin level was greater than 30 microunits./ml. Below this value, there was no consistent uptake of insulin by the uterus. The observations are discussed in relation to the regulation of insulin release in utero and the effects of pregnancy on maternal beta-cell function.

Animals↗

Prostaglandins in maternal and fetal plasma and in allantoic fluid during the second half of gestation in the mare.

The concentrations of the primary prostaglandins (PG) F-2alpha and E-2 and the metabolite 13,14-dihydro-15-oxo-prostaglandin (PGFM) in maternal and fetal plasma and in allantoic fluid were measured in chronically catheterized mares and fetuses. A gradual rise in all 3 PGs occurred with increasing gestational age. PGE-2 and PGF-2 alpha levels were highest in the allantoic fluid and lowest in the maternal plasma, whereas PGFM concentrations were greatest in maternal plasma. Significant venous-arterial plasma differences in PGFM concentration were detected across the uterine circulation between 180 and 280 days gestation. The 3--5-fold rise in maternal PGFM associated with fasting or intrauterine surgery was virtually abolished by meclofenamic acid, a prostaglandin synthetase inhibitor. Increases in PGE-2 and PGF-2 alpha in the fetal fluids preceded premature delivery of the foal, while PG changes in maternal plasma were minimal even 10--20 h before delivery.

Allantois↗