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Biomedical subjects

J B Leiper

Publications and source records attributed to J B Leiper.

14 recordsLinked to original sources

Comparison of aspiration and scintigraphic techniques for the measurement of gastric emptying rates of liquids in humans.

A comparison was made of two techniques to measure the rate of gastric emptying. A noninvasive scintigraphic technique using a gammacamera and an invasive aspiration technique based on dye dilution were performed simultaneously. Seven healthy male volunteers each consumed two different liquid meals on two separate occasions. Scintigraphic measurements were performed continuously with aspiration every 10 minutes for a total of one hour. Gastric emptying rates were expressed as slope values after semilog linearisation of the emptying curves. Agreement between the two methods was assessed from the individual differences and mean of the two techniques, as well as from the geometric mean, including 95% limits of agreement. The scintigraphic technique gave a 70% slower emptying rate than the dye dilution technique. However, the 95% limits of agreement are large (1.56 to 0.30), reflecting the small sample size and the large coefficient of variation in the techniques used.

Adult

Gastric emptying, absorption, and carbohydrate oxidation during prolonged exercise.

This study was designed to examine aspects of digestive function that may limit assimilation of water and oxidation of orally ingested carbohydrate (CHO) during exercise. Eight males completed a crossover study in which each cycled on four occasions for 80 min at 70% maximal O2 consumption. Beverage was consumed at 0, 20, 40, and 60 min. Beverages were water, 4.5% glucose (4.5G), 17% glucose (17G), and 17% maltodextrin (17MD). CHO beverages contained 20 meq/l NaCl and were 13C enriched to measure exogenous CHO oxidation. Gastric (beverage) volume was measured at 80 min. Water uptake was estimated by including 2H2O in the beverage and measuring 2H accumulation in blood. Jejunal perfusion tests were conducted at rest with the same subjects and beverages. In 60 min, 1,294 +/- 31 (SE) ml were ingested; at 80 min, volumes emptied with H2O (1,257 +/- 32 ml) and 4.5G (1,223 +/- 32 ml) were greater than with 17G (781 +/- 56 ml) and 17MD (864 +/- 71 ml; P less than 0.05). Total CHO oxidized was similar with all beverages, but there was a greater increase in exogenous CHO oxidation over time with 17G and 17MD than with 4.5G; 54, 19, and 18% of the CHO ingested with 4.5G, 17G, and 17MD, respectively, was oxidized. This represents 57, 32, and 27%, respectively, of the CHO emptied from the stomach. 2H accumulation in the blood was more rapid with H2O and 4.5G than with 17G or 17MD. Net jejunal water absorption was greater from 4.5G than from water. Net water absorption was also observed from 17MD, whereas net secretion was observed with 17G.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

The influence of dietary manipulation on plasma ammonia accumulation during incremental exercise in man.

The influence of a pattern of exercise and dietary manipulation, intended to alter carbohydrate (CHO) availability, on pre-exercise acid-base status and plasma ammonia and blood lactate accumulation during incremental exercise was investigated. On three separate occasions, five healthy male subjects underwent a pre-determined incremental exercise test (IET) on an electrically braked cycle ergometer. Each IET involved subjects exercising for 5 min at 30%, 50%, 70% and 95% of their maximal oxygen uptake (VO2max) and workloads were separated by 5 min rest. The first IET took place after 3 days of normal dietary CHO intake. The second and third tests followed 3 days of low or high CHO intake, which was preceded by prolonged exercise to exhaustion in an attempt to deplete muscle and liver glycogen stores. Acid-base status and plasma ammonia and blood lactate levels were measured on arterialised venous blood samples immediately prior to and during the final 15 s of exercise at each workload and for 40 min following the completion of each IET. Three days of low CHO intake resulted in the development of a mild metabolic acidosis in all subjects. Plasma ammonia (NH3) accumulation on the low-CHO diet tended to be greater than normal at each exercise workload. Values returned towards resting levels during each recovery period. After the normal and high-CHO diets plasma NH3 levels did not markedly increase above resting values until after exercise at 95% VO2max. Plasma NH3 levels after the high-CHO diet were similar to those after the normal CHO diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium

Effects of exercise intensity on absorption of ingested fluids in man.

Plasma 2H accumulation was measured in six male volunteers after ingestion of drinks containing trace amounts of 2H2O. Subjects fasted overnight and remained seated at rest or exercised on a cycle ergometer at 42, 61 or 80% of their maximum oxygen uptake (VO2, max). The rate of plasma 2H accumulation was faster at rest than during exercise at 61 or 80% of VO2, max (P less than 0.05), and was faster at 42 and 61% than at 80% of VO2, max (P less than 0.05). The time to peak plasma 2H concentration was longer during exercise than at rest. This suggests that strenuous exercise may reduce the availability of fluid ingested during exercise.

Adult

Studies in human models.

Advances in the development of oral rehydration solutions (ORS) for the treatment of diarrheal disease depend on a knowledge of the disease process itself and of the factors that determine the movement of water and solutes across the gut. The formulation of ORS in current use is based on information derived from a number of different experimental approaches that attempt to take account of these factors. The fate of orally ingested solutions depends first on the processes of gastric emptying that control the rate of entry of fluid to the small intestine and second on the rates of absorption and secretion in the intestine. In the absence of a model that can reliably assess the effects of these two processes together, they are normally investigated separately. The methods of choice for measurement of gastric emptying are gamma scintigraphy and gastric aspiration. Multi-lumen perfusion techniques permit measurement of net flux in short segments of intestine. A promising new technique that takes account of both gastric emptying and intestinal transport involves measurement of accumulation in the circulation of isotopic tracers for water added to ingested solutions. The efficacy of new solutions must, however, ultimately be assessed in clinical trials on patients.

Fluid Therapy

Effects of fluid, electrolyte and substrate ingestion on endurance capacity.

The availability of carbohydrate (CHO) as a substrate for the exercising muscles is known to be a limiting factor in the performance of prolonged cycle exercise, and provision of exogenous CHO in the form of glucose can increase endurance capacity. The present study examined the effects of ingestion of fluids and of CHO in different forms on exercise performance. Six male volunteers exercised to exhaustion on a cycle ergometer at a workload which required approximately 70% of Vo2max. After one preliminary trial, subjects performed this exercise test on six occasions, one week apart. Immediately before exercise, and at 10-min intervals throughout, subjects ingested 100 ml of one of the following: control (no drink), water, glucose syrup, fructose syrup, glucose-fructose syrup or a dilute glucose-electrolyte solution. Each of the syrup solutions contained approximately 36 g CHO per 100 ml; the isotonic glucose-electrolyte solution contained 4 g glucose per 100 ml. A randomised Latin square order of administration of trials was employed. Expired air samples for determination of Vo2, respiratory exchange ratio and rate of CHO oxidation were collected at 15-min intervals. Venous blood samples were obtained before and after exercise. Subjects drinking the isotonic glucose-electrolyte solution exercised longer (90.8 (12.4) min, mean (SEM] than on the control test (70.2 (8.3) min; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Absorption of water and solute from glucose-electrolyte solutions in the human jejunum: effect of citrate or betaine.

The inclusion in oral rehydration solutions of solutes that are actively co-transported with sodium has been suggested as a means of increasing the effect of glucose on water absorption by the small intestine. Using a modified perfusion system we have examined water and solute absorption in the normal human intestine from two effervescent glucose-electrolyte solutions, containing either citrate or betaine hydrochloride, and compared the absorption rates with those from a commonly used bicarbonate-containing oral rehydration solution. Absorption of citrate (355 +/- 87 mumol/cm/h) and betaine (313 +/- 125 mumol/cm/h) occurred from the respective solutions. The inclusion of 46 mmol/l citrate or 36 mmol/l betaine in effervescent oral rehydration solutions had no effect on water or solute absorption.

Betaine

Fluid homoeostasis during prolonged low-intensity walking on consecutive days.

1. The effect on fluid homoeostasis of walking 37 km on each of 4 consecutive relatively cool days was studied in six male subjects. The daily exercise intensity was consistent and was equivalent to 17(1)% [mean (SE)] of maximum oxygen uptake for these subjects. 2. The diet during the study consisted of a mainly carbohydrate breakfast, consumed immediately before each day's exercise, and unrestricted access to a normal mixed diet after completion of each day's exercise. Water was allowed ad libitum during the walk. Food and fluid intake were recorded. 3. Body weight remained constant over the 4-day walk. The difference between total daily fluid intake and the corresponding 24 h urine output was 1684 (250) ml, 1621 (522) ml, 1107 (252) ml and 1406 (208) ml, respectively, on each of the 4 exercise days. 4. There was a calculated increase of 21.3(6.6)% in plasma volume over the 4-day walk; the largest daily change [11.3(2.9)%] occurred during the walk on day 1. The increase in plasma volume was maintained for at least 4 days after completion of the walk. 5. From day 2, serum sodium concentration tended to increase during the exercise period and fell to the pre-exercise concentration during the overnight rest periods. The concentration of the other measured serum constituents remained relatively constant, and serum osmolality did not alter over the study period.

Blood Proteins

Effect of bicarbonate or base precursor on water and solute absorption from a glucose-electrolyte solution in the human jejunum.

A modified perfusion technique was used to examine the effect on water and solute absorption in the healthy human jejunum of replacing bicarbonate (18 mmol/l) by equivalent amounts of different base precursors in a glucose-electrolyte solution. Acetate, citrate and lactate were absorbed from the perfusion solutions. Absorption of these base precursors appeared to have no effect on water uptake, but greater sodium (p less than 0.05) absorption occurred from solutions containing either acetate or lactate compared with the bicarbonate-containing solution. These data suggest that oral rehydration solutions with base precursors other than bicarbonate are as effective as bicarbonate-containing solutions in promoting absorption of water and electrolytes.

Acetates

Experimental models for the investigation of water and solute transport in man. Implications for oral rehydration solutions.

For patients suffering from mild to moderate dehydration, oral rehydration therapy has proved a simple and efficacious treatment. There remains, however, a need to develop improved oral rehydration solutions (ORS), and suitable experimental models are required to develop and assess new formulations. The ideal model for such investigations would take into account rates of gastric emptying, influx and efflux of water and solutes in the intestine, and the consequent changes in body composition. As no such definitive model is currently available, a variety of techniques are used to examine parts of the process of intestinal absorption. Clinical studies which assess the recovery of dehydrated patients during therapy using different ORS will ultimately evaluate the efficacy of treatment. However, ethical considerations, the relative insensitivity of this technique and the exacting nature of such studies make this approach unsuitable for the development of specific ORS. Gastric emptying of solutions can be determined by a variety of techniques, among which the radioactive tracer method offers the advantage of having no direct effect on the emptying rate, giving almost continuous measurement and allowing the use of relatively small volumes of fluids. Perfusion techniques allow measurement of the net flux of water and solute in predetermined sections of the intact human intestine. Measurement of the rate of accumulation in the circulation of orally ingested tracer molecules for water and solutes can estimate unidirectional flux. This method allows for the rates of gastric emptying and intestinal absorption of the test substance, but the rate of efflux of the tracer from the vascular space must be known to calculate net uptake. Each of these models has limitations, and care must be taken in interpreting the results in a clinical context. However, their use in the development of improved formulations is well established.

Fluid Therapy

The effect of dietary carbohydrate intake on the metabolic response to prolonged walking on consecutive days.

Six healthy subjects walked 37 km per day for four consecutive days on two occasions one month apart; on one walk, subjects consumed a high carbohydrate (CHO) diet (85 +/- 1% CHO, Mean +/- SE) and on the other walk an isocaloric low CHO diet (2 +/- 0% CHO) was consumed. Subjects were fasted each day until after the completion of the walk. Blood samples were obtained at rest prior to exercise and after completion of each of three laps of 12.3 km. Exercise intensity corresponded to approximately 17% of VO2max. The first day of each walk demonstrated that the pattern of substrate mobilisation in response to this type of exercise is highly reproducible, there being no difference in any of the parameters measured between the two walks. Circulating glucose, lactate, insulin and triglyceride levels remained essentially unchanged; alanine fell progressively and glycerol, free fatty acid (FFA) and 3-hydroxybutyrate (BHB) rose progressively. After the first day there was a general tendency for the blood glucose concentration to decline as exercise progressed; by the end of the walk on Day 2, blood glucose was lower on the low CHO diet than on the high CHO diet. On Day 4 plasma insulin was higher (p less than 0.05) on the high CHO diet than on the low CHO diet and declined progressively on both diets. Blood lactate and alanine concentrations were generally higher at rest on the high CHO diet, but fell so that no differences existed by the end of exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Ontogeny of mitogenic responsiveness to PHA and sheep erythrocytes and lymphokine production in foetal guinea-pigs.

Pre-culture of spleen cells for 24 h before addition of activator greatly improved the mitogenic response to phytohaemagglutinin (PHA) and sheep erythrocytes (SRBC). Spleen cells were separated into plastic-adherent and non-adherent populations and in some experiments purified further to 'macrophages' and 'lymphocytes' respectively. A critical mixture of lymphocytes and macrophages (10:1) gave twice the mitogenic response of lymphocytes alone to PHA and SRBC in cultures of foetal, juvenile and adult guinea-pig spleen cells. Vigorous mitogenic responses to PHA and SRBC were found at 36 days of gestation. The mitogenic response increased from 46-56 days of gestation to above adult level. Lipopolysaccharide (LPS) obtained by the Westphal method was a superior mitogen to LPS extracted by the Boivin technique. Plaque-forming cells (PFC) could not be induced in vitro at any age even with the addition of LPS. Evidence was obtained for mitogenic and blastogenic lymphokines produced by lymphocytes activated with PHA or produced by lymphocytes activated with PHA or SRBC (but not LPS). These lymphokines were produced by activated splenic lymphocytes of a 40-day-old foetus; older animals showed no evidence for a quantitative increase in lymphokine production. The onset and maturation of mitogenic responsiveness in the guinea-pig and human foetus is compared by age-equivalence.

Animals