Incidence of the plateau at V˙O 2max is dependent on the anaerobic capacity.

The purpose of this study was to address if there is an association between the plateau at V˙O (2max) and the anaerobic capacity. 9 well-trained cyclists (age 22.2 ± 3.5 yr, height 182.5 ± 5.0 cm, mass 75.7 ± 8.7 kg, V˙O (2max) 59.3 ± 4.8 ml x kg(-1) x min(-1)completed both an incremental step test of 20 W x min(-1) starting at 120 W for determination of maximal oxygen uptake (MOU) and a maximally accumulated oxygen deficit (MAOD) trial at 125% MOU for estimation of anaerobic capacity. Throughout all trials expired air was recorded on a breath-by-breath basis. A significant inverse relationship was observed between the MAOD and the Δ V˙O (2) during the final 60 s of the MOU test (r=-0.77, p=0.008). Of the 9 participants it was noted that only 4 exhibited a plateau at MOU. There were non-significant differences for V˙O (2) and the associated secondary criteria for those exhibiting a plateau and the non-plateau responders, despite a significant difference for MAOD (p=0.041) between groups. These data suggest that incidence of the plateau at MOU is dependent on anaerobic substrate metabolism and that ranges of responses reported in the literature may be a consequence of variations in anaerobic capacity amongst participants.

Influence of blood donation on oxygen uptake kinetics during moderate and heavy intensity cycle exercise.

The purpose of this study was to determine the effects of a reduced whole body blood volume on the kinetic response of VO(2) during moderate and heavy intensity exercise. Six males and four females (age, 21+/-2 yrs; height, 175.2+/-5.1 cm; weight, 66.4+/-2.8 kg; VO(2)max, 53.0+/-4.1 ml x kg (-1) x min(-1)), completed a square-wave cycling ramp test to determine ventilatory threshold (VT) and VO(2max). Kinetics trials were completed 24 h pre and post donation of 450 cm (3) of blood. The kinetics trials were moderate intensity (80%VT) and heavy intensity (Delta50% VT - VO(2max)). Breath-by-breath gas exchange, heart rate, blood pressure, haemoglobin O(2) saturation, and blood [lactate] were measured throughout the trials. Post-donation haemoglobin, haematocrit and erythrocyte count were all significantly reduced (por= 0.05), or in the amplitude of the slow component. The capacity of the cardiovascular system to meet the metabolic demands of skeletal muscle at the onset of exercise does not limit the oxygen uptake.

Small structural changes of the imidazopyridine diacylglycerol acyltransferase 2 (DGAT2) inhibitors produce an improved safety profile.

Small molecule DGAT2 inhibitors have shown promise for the treatment of metabolic diseases in preclinical models. Herein, we report the first toxicological evaluation of imidazopyridine-based DGAT2 inhibitors and show that the arteriopathy associated with imidazopyridine 1 can be mitigated with small structural modifications, and is thus not mechanism related.

Vertically integrated flows, discharge potential, and the Dupuit-Forchheimer approximation.

We summarize observations made by various researchers regarding the discharge potential, vertically integrated flows, and the Dupuit-Forchheimer approximation. If a regional flow model is formulated in terms of the discharge potential and the boundary conditions can be written in terms of the discharge potential and the boundary discharges, then the discharges are correct throughout the model domain, without embracing any additional simplifying assumptions.

Global storm time depletion of the outer electron belt.

The outer radiation belt consists of relativistic (>0.5 MeV) electrons trapped on closed trajectories around Earth where the magnetic field is nearly dipolar. During increased geomagnetic activity, electron intensities in the belt can vary by orders of magnitude at different spatial and temporal scales. The main phase of geomagnetic storms often produces deep depletions of electron intensities over broad regions of the outer belt. Previous studies identified three possible processes that can contribute to the main-phase depletions: adiabatic inflation of electron drift orbits caused by the ring current growth, electron loss into the atmosphere, and electron escape through the magnetopause boundary. In this paper we investigate the relative importance of the adiabatic effect and magnetopause loss to the rapid depletion of the outer belt observed at the Van Allen Probes spacecraft during the main phase of 17 March 2013 storm. The intensities of >1 MeV electrons were depleted by more than an order of magnitude over the entire radial extent of the belt in less than 6 h after the sudden storm commencement. For the analysis we used three-dimensional test particle simulations of global evolution of the outer belt in the Tsyganenko-Sitnov (TS07D) magnetic field model with an inductive electric field. Comparison of the simulation results with electron measurements from the Magnetic Electron Ion Spectrometer experiment shows that magnetopause loss accounts for most of the observed depletion at L>5, while at lower L shells the depletion is adiabatic. Both magnetopause loss and the adiabatic effect are controlled by the change in global configuration of the magnetic field due to storm time development of the ring current; a simulation of electron evolution without a ring current produces a much weaker depletion.

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.

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.

Foetal and maternal plasma concentrations of 13, 14-dihydro-15-oxo-prostaglandin F in the mare during late pregnancy and at parturition.

The concentrations of 13, 14-dihydro-15-oxo-prostaglandin F(PGFM), the stable metabolite of prostaglandin F, were measured in the plasma of catheterized mares and foetuses and non-catheterized thoroughbred mares and ponies during the last months of gestation. The plasma concentration of PGFM increased gradually towards term in all groups of animals. During the operation for insertion of catheters, maternal and foetal concentrations of PGFM were high, but the values fell to basal levels 24--48 h after the operation. It was found the preoperative starvation (24 h) led to a rise in the concentration of PGFM in the maternal plasma. The raised concentrations of PGFM during the operation were associated with low progestogen and high oestrogen concentrations in umbilical venous plasma. The subsequent survival period of the catheterized foal was inversely related to the maximum concentration of PGFM were studied during normal parturition in thoroughbred mares, during oxytocin-induced delivery in non-catheterized ponies and during premature delivery or abortion in the catheterized animals. The greatest increase in the concentration of PGFM was seen in the thoroughbred animals during second-stage labour; oxytocin also resulted in a very rapid rise in the level of PGFM, which remained high until delivery. In the catheterized animals, the birth of live foetuses was associated with a rise in the concentration of PGFM in both foetal and maternal plasma during the last 2 h before delivery. Less consistent changes were found during abortion.

Single- versus multiple-dose comparative trial of desipramine hydrochloride: a double-placebo method.

In a double-blind comparative trial utilizing the double-placebo method, depressed neurotic patients whose effective titrated dose of desipramine hydrochloride was 75, 100, or 150 mg were maintained, with equal efficacy, on once-a-day or multiple daily dose regimens. The data confirm that the safety of the once-a-day maintenance regimen (as measured by vital signs, laboratory tests, ECGs, and clinical adverse reactions) is comparable to the safety of the multiple daily dose regimen.

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.

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.

Mesoridazine (Serentil) in personality disorders--a controlled trial in adolescent patients.

A double-blind study vs. placebo was carried out over a 6-week period in thirty adolescent patients to determine the efficacy and safety of mesoridazine, in the form of 10 mg tablets, in the treatment of symptoms associated with various personality disorders. The average daily dose for the 15 patients in the mesoridazine group was 27.3 mg in the first and 44.7 mg in the sixth week. Mesoridazine relieved anxiety to a highly significant degree when compared with placebo and proved significantly more effective than placebo also in terms of mean improvement scores for depression and hostility. Significant reductions were likewise achieved in the overall severity of the disorders and in the severity of nearly all the other symptoms. The incidence of adverse reactions did not differ significantly from that following placebo administration. No extrapyramidal symptoms were noted.

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)

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)

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.

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.

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.

Electrocardiographic changes in amitriptyline poisoning.

In imipramine and amitriptyline poisoning the electrocardiographic abnormalities comprise arrhythmias, widening of the QRS complex, and marked changes in die S-T segment. These features were found to be of value in the differential diagnosis of unknown poisoning. The unusual configuration of qR with raised S-T segment in V1, simulating myocardial infarction, was seen in one of our patients and has been noted in four cases reported by other workers.

A follow-up survey of patients with dyspepsia in one general practice.

Eighty-three patients who had been investigated by cholecystogram, barium meal and fibreoptic endoscopy more than two years previously were interviewed to enquire into their reactions to the investigations carried out, their present symptoms, and their present smoking and alcohol consumption. Comparisons were made with previously recorded observations. Those who still complained of severe dyspepsia were asked to attend for a repeat endoscopy. Sixty-three per cent of patients were asymptomatic; 13 per cent had recurrent dyspepsia, and 24 per cent had persistent dyspepsia. Thirty-nine per cent of smokers were found to have stopped altogether following medical advice.Both radiological and endoscopic methods of investigation proved acceptable. A majority of patients preferred endoscopy to barium meal.