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Biomedical subjects

I T Campbell

Publications and source records attributed to I T Campbell.

At least 19 recordsLinked to original sources
PubMed2002

Acceptability and tolerance of a low tyrosine and phenylalanine diet in patients with advanced cancer -- a pilot study.

BACKGROUND: Low phenylalanine (phe) and tyrosine (tyr) diets limit tumour growth in animal models and may offer a novel cancer therapy. We studied the efficacy and acceptability of a low phe and tyr diet in patients with advanced cancer. METHODS: Patients with advanced metastatic melanoma (n=22) and metastatic breast cancer (n=15) were invited to follow a low phe and tyr diet (10 mg kg-1 phe and tyr per day) for 1 month. In those individuals who followed the diet for 1 month, we attempted to establish the effects on nutritional status (body weight, fat free mass, percentage body fat, serum albumin), immune cell function (white cell count, lymphocytes and neutrophils), plasma levels of phe-tyr and tryptophan and quality of life (Hospital Anxiety and Depression score). RESULTS: Only three of the 22 patients with metastatic melanoma and three of the 15 patients with metastatic breast cancer agreed to start the diet. All patients experienced problems and side-effects and increases in anxiety and depression. There were declines in weight, with loss of fat and fat free mass but slight increases in white cell counts and neutrophils. CONCLUSIONS: Low phe and tyr diets do not appear to be a viable treatment option for patients with advanced cancer.

Adult↗
PubMed2002

Physiological and metabolic responses to a hill walk.

The physiological and metabolic demands of hill walking have not been studied systematically in the field despite the potentially deleterious physiological consequences of activity sustained over an entire day. On separate occasions, 13 subjects completed a self-paced hill walk over 12 km, consisting of a range of gradients and terrain typical of a mountainous walk. During the hill walk, continuous measurements of rectal (T(re)) and skin (T(sk)) temperatures and of respiratory gas exchange were made to calculate the total energy expenditure. Blood samples, for the analysis of metabolites and hormones, were taken before breakfast and lunch and immediately after the hill walk. During the first 5 km of the walk (100- to 902-m elevation), T(re) increased (36.9 +/- 0.2 to 38.5 +/- 0.4 degrees C) with a subsequent decrease in mean T(sk) from this time point. T(re) decreased by approximately 1.0 degrees C during a 30-min stop for lunch, and it continued to decrease a further 0.5 degrees C after walking recommenced. The total energy intake from both breakfast and lunch [5.6 +/- 0.7 (SE) MJ] was lower than the energy expended [14.5 +/- 0.5 (SE) MJ; P < 0.001] during the 12-km hill walk. Despite the difference in energy intake and expenditure, blood glucose concentration was maintained. The major source of energy was an enhanced fat oxidation, probably from adipose tissue lipolysis reflected in high plasma nonesterified fatty acid concentrations. The major observations were the varying thermoregulatory responses and the negative energy balance incurred during the hill walk. It is concluded that recreational hill walking can constitute a significant metabolic and thermoregulatory strain on participants.

Adolescent↗
PubMed2002

Metabolic and appetite responses to prolonged walking under three isoenergetic diets.

The effects of three isoenergetic diets on metabolic and appetite responses to prolonged intermittent walking were investigated. Eight men undertook three 450-min walks at intensities varying between 25-30 and 50-55% of maximal O2 uptake. In a balanced design, the subjects were given breakfast, snacks, and lunch containing total carbohydrate (CHO), protein (P), and fat (F) in the following amounts (g/70 kg body mass): mixed diet, 302 CHO, 50 P, 84 F; high-CHO diet, 438 CHO, 46 P, 35 F; high-fat diet, 63 CHO, 44 P, 196 F. Substrate balance was calculated by indirect calorimetry over the 450-min exercise period. Blood samples were taken before exercise and every 45 min during the exercise period. The high-fat diet resulted in a negative total CHO balance (-140 +/- 1 g) and a lower negative fat balance (-110 +/- 33 g) than the other two diets (P < 0.05). Plasma glucagon, nonesterified fatty acids, glycerol, and 3-hydroxybutyrate were higher with the high-fat diet (P < 0.05 vs. high CHO), whereas plasma insulin was lower after high fat (P < 0.05 vs. mixed and high CHO). Subjective ratings of fatigue and appetite showed no differences between the three trials. Although diet influenced the degree of total CHO and fat oxidation, fat was the main source of energy in all trials.

3-Hydroxybutyric Acid↗
PubMed2002

Energy balance, metabolism, hydration, and performance during strenuous hill walking: the effect of age.

We aimed to examine the effect of age on energy balance, metabolism, hydration, and performance during 10 days of strenuous hill walking. Seventeen male subjects were divided into two groups according to their age. The nine subjects in group 1 constituted the younger group (age 24 +/- 3 yr), whereas eight older subjects were in group 2 (age 56 +/- 3 yr). Both groups completed 10 consecutive days of high-intensity hill walking. Mean (range) daily walking distances and ascent were 21 km (10-35 km) and 1,160 m (800-2,540 m), respectively. Energy intake was calculated from weighed food intake, and energy expenditure was measured by the doubly labeled water method. Blood and urine were sampled on alternative days to determine any changes in metabolism and hydration during the 10 days. Subjects also completed a battery of tests that included muscular strength (handgrip), jump performance, cognitive processing time, and flexibility. The younger group remained hydrated, whereas the older group became progressively dehydrated, indicated by a near twofold increase in urine osmolality concentration on day 11. This increased urine osmolality in the older group was highly correlated with impairment in vertical-jump performance (r = -0.86; P < 0.05) and decreased cognitive processing time (r = 0.79; P < 0.05). Despite energy expenditure of approximately 21 MJ/day, body mass was well maintained in both groups. Both groups displayed a marked increase in fat mobilization, reflected in significantly lowered prewalk insulin concentrations and elevated postwalk glycerol and nonesterified fatty acid concentrations. Despite the dehydration and impaired performance in the older group, blood glucose concentrations were well maintained in both groups, probably mediated via the increased mobilization of fat.

Adult↗
PubMed2000

Human erythrocyte and plasma amino acid concentrations during exercise.

PURPOSE: This investigation examined the effects of exercise and maltodextrin (Md) or placebo (Pl) ingestion on plasma and erythrocyte concentrations of amino acids. METHODS: The erythrocyte and plasma concentrations of 17 amino acids, as well as plasma glucose and insulin, were analyzed in eight healthy trained male subjects before, during, and 25 min after 90-min cycle ergometer exercise at 65% peak oxygen uptake. The two treatments involved ingestion of orange-flavored water (Pl) or orange-flavored 10% maltodextrin solution (Md). RESULTS: Two-way ANOVA revealed 1) that plasma concentrations of alanine and tyrosine changed significantly during the treatments, 2) that the plasma concentrations were significantly different between treatments for glycine and threonine, 3) that all erythrocyte concentrations increased significantly throughout the treatments except for arginine and tyrosine, and 4) that there were no significant differences in erythrocyte concentrations between the treatments. Three-way ANOVA highlighted the significant differences in the time responses between plasma and erythrocyte concentrations; the changes in erythrocyte levels from rest being significantly different from plasma for all amino acids except aspartic acid, glycine, and ornithine. Plasma glucose concentrations became elevated and remained above rest values in Md but fell below rest values in Pl: the differences in concentration between treatments were significant. Correspondingly, plasma insulin was significantly higher in Md during exercise. CONCLUSION: These results highlight that far from being slow in the uptake of amino acids, the erythrocyte in fact sequesters amino acids at an appreciable rate during exercise without a corresponding elevation in the plasma amino acids. For a greater understanding of amino acid changes during exercise, the analysis of both plasma and erythrocytes is recommended.

Administration, Oral↗
PubMed1999

The role of depression in pain, psychophysiological syndromes and medically unexplained symptoms associated with chronic fatigue syndrome.

BACKGROUND: The association between depression and pain, function, medically unexplained symptoms and psychophysiological syndromes such as irritable bowel syndrome has not been explored before in chronic fatigue syndrome. METHODS: Cross-sectional controlled study of the current prevalence of psychophysiological syndromes, pain, function and lifetime prevalence of medically unexplained symptoms in 77 out-patients with chronic fatigue syndrome (CFS) without DSM-III-R depression, 42 CFS out-patients with DSM-III-R depression and 26 out-patient with primary DSM-III-R depression. RESULTS: Both CFS groups differed significantly from the primary depression group but not each other in the prevalence of tension headaches (P < 0.001), reporting of widespread bodily pain (P < 0.001) and the number of lifetime medically unexplained symptoms (P < 0.001). The three groups did not significantly differ in the prevalence of irritable bowel syndrome or fibromyalgia. CFS patients with depression were more impaired in social function than other CFS patients. CONCLUSION: Depression is not associated with the reporting of pain, psychophysiological syndromes and medically unexplained symptoms in CFS patients. Depression is associated with decreased social function in CFS patients. LIMITATIONS: Study depended on recall of symptoms, not confirmed by medical records and current investigations. Patients with depression were taking antidepressants. CLINICAL RELEVANCE: Treating depression in chronic fatigue syndrome is unlikely to diminish reporting of pain and medically unexplained symptoms but may improve social function.

Adult↗
PubMed1999

Limitations of nutrient intake. The effect of stressors: trauma, sepsis and multiple organ failure.

The response to injury includes a diminution in appetite, a decrease in nutrient intake, an acute mobilisation of endogenous energy stores (glucose and fat), but an impaired ability to use them. Lean tissue is broken down to its constituent amino acids, which provide precursors for the synthesis of glucose in the liver (gluconeogenesis). Glucose is used as a source of energy by the brain and red blood cells, as well as by wound tissue. After a discrete injury normal function is normally resumed with a reduced body mass. In very severe injury or sepsis, in those who are physiologically or immunologically impaired or those with a genetic predisposition to the condition, organ failure may develop due to an apparent ongoing inflammatory process. The origin of this process is not always apparent, but loss of integrity of the gastrointestinal tract has been suggested. Apparently adequate nutritional support in the presence of a severe inflammatory stimulus only attenuates the gluconeogenic process, and the breakdown of lean tissue continues. Supply of protein (amino acids) stimulates protein synthesis, but it also stimulates breakdown. Nutrient intake via the enteral route may be limited by gastrointestinal symptoms and via the parenteral route by fluid overload, although this can be circumvented by fluid removal by haemofiltration. It is probable that, if nutritional support in severe trauma/sepsis/multiple organ failure is to be effective, satisfactory pharmacological methods of controlling metabolism will have to be found.

Appetite↗
PubMed1999

Prediction of peak oxygen uptake in chronic fatigue syndrome.

OBJECTIVES: To establish a simple, valid, and acceptable method of predicting peak oxygen uptake (VO2peak) in patients with chronic fatigue syndrome (CFS), which could provide a basis for subsequent exercise prescription at an appropriate intensity as part of a clinical rehabilitation programme. METHODS: A total of 130 patients who met UK research criteria for CFS were taken from consecutive referrals for chronic fatigue to the University Department of Medicine at Withington Hospital, Manchester. VO2peak was determined using an incremental graded exercise test to exhaustion. Respiratory gas exchange, work rate, and heart rate were monitored throughout. RESULTS: In all patients, VO2peak was found to correlate strongly and significantly with peak work rate (WRpeak) during testing (r2 = 0.88, p<0.001). In patients who exercised for longer than two minutes (n = 119), regression analysis established the relation as Vo2peak = 13.1 x WRPpeak + 284, where VO2 is given in ml/min and WR in W. The mean error between the measured VO2peak and the predicted value was 10.7%. The relation between increase in work rate and oxygen uptake across the group was highly significant (r2 = 0.87, p<0.001), and given as VO2increase = 12.0 x WRincrease, this value being similar to that expected for healthy individuals. Almost all (97%) subjects reported no exacerbation of symptoms after maximal exercise testing. CONCLUSIONS: Using a simple to administer maximal exercise test on a cycle ergometer, it is possible to predict accurately the VO2peak of a patient with CFS from peak work rate alone. This value can then be used as an aid to setting appropriate exercise intensity for a rehabilitation programme. The increase in VO2 per unit increase in workload was consistent with that expected in healthy individuals, suggesting that the physiological response of the patients measured here was not abnormal. Contrary to the belief of many patients, maximal exercise testing to the point of subjective exhaustion proved to be harmless, with no subjects suffering any lasting deterioration in their condition after assessment.

Adult↗
PubMed1999

Hormonal and metabolic responses to maintained hyperglycemia during prolonged exercise.

We studied the effects of maintained hyperglycemia (12 mmol/l) on endurance exercise to determine the hormonal and metabolic responses, the maximal rate of glucose infusion (i.e., utilization), and the effects on muscle glycogen stores. Eight men undertook two trials during which they exercised on a cycle ergometer at an intensity of approximately 70% peak O(2) uptake for 120 min. In the first trial (trial A), subjects had their blood glucose concentration clamped at 12 mmol/l 30 min before exercise and throughout exercise. The same rate and volume of infusion of saline as had occurred for trial A were used in a placebo trial (trial B). Maintained hyperglycemia resulted in significantly lowered plasma concentrations of nonesterified fatty acid, glycerol, 3-hydroxybutyrate, epinephrine, norepinephrine, and growth hormone (P < 0.001) during exercise, whereas concentrations of plasma insulin were significantly elevated (P < 0.001). Calculations of the rates of total carbohydrate oxidation showed that trial A resulted in significantly higher values when compared with trial B (P < 0.01) and that the maximal rates of glucose infusion varied between 1.33 and 2.78 g/min at 100-120 min. Muscle glycogen concentrations were significantly depleted (P < 0.01) after both trials (trial A, 170.3 micromol/g dry wt decrease; trial B, 206 micromol/g dry wt decrease), although this apparent difference may be accounted for by storage of 22.6 g glucose during the 30-min prime infusion. The results from this study confirm that maintained hyperglycemia attenuates the hormonal response and promotes carbohydrate oxidation and utilization and that muscle glycogen may not be spared.

3-Hydroxybutyric Acid↗
PubMed1998

Nutrition support in patients with multiple organ failure.

The problem with any attempt to feed patients in multiple organ failure is that, because of an ongoing inflammatory process, the conventional techniques of supplying energy and protein do not maintain lean tissue mass. In addition, the conventional markers of nutritional status, both anthropometric (body mass and composition, arm circumference, etc.) and visceral protein (albumin, prealbumin) as well as immunological markers (delayed reactive skin hypersenstivity to common antigens and lymphocyte counts) are confounded by fluid retention (5-15 l) and the metabolic response to the illness. Recent research has focussed on the nature and origin of this inflammatory response, the problems of trying to feed an individual undergoing such a response, the details of the protein breakdown observed in sepsis and multiple organ failure and methods of modifying the response favourably.

Animals↗
PubMed1998

Metabolic and performance responses during endurance exercise after high-fat and high-carbohydrate meals.

We studied the effects of preexercise meal composition on metabolic and performance-related variables during endurance exercise. Eight well-trained cyclists (maximal oxygen uptake 65.0 to 83.5 ml . kg-1 . min-1) were studied on three occasions after an overnight fast. They were given isoenergetic meals containing carbohydrate (CHO), protein (P), and fat (F) in the following amounts (g/70 kg body wt): high-carbohydrate meal, 215 CHO, 26 P, 3 F; high-fat meal, 50 CHO, 14 P, 80 F. On the third occasion subjects were studied after an overnight fast. Four hours after consumption of the meal, subjects started exercise for 90 min at 70% of their maximal oxygen uptake, followed by a 10-km time trial. The high-carbohydrate meal compared with the high-fat meal resulted in significant decreases (P < 0.05) in blood glucose, plasma nonesterified fatty acids, plasma glycerol, plasma chylomicron-triacylglycerol, and plasma 3-hydroxybutyrate concentrations during exercise. This was accompanied by an increase in plasma insulin (P < 0.01 vs. no meal), plasma epinephrine, and plasma growth hormone concentrations (each P < 0.05 vs. either of the other conditions) during exercise. Despite these large differences in substrate and hormone concentrations in plasma, substrate oxidation during the 90-min exercise period was similar in the three trials, and there were no differences in performance on the time trial. These results suggest that, although the availability of fatty acids and other substrates in plasma can be markedly altered by dietary means, the pattern of substrate oxidation during endurance exercise is remarkably resistant to alteration.

Adult↗
PubMed1998

Randomised, double-blind, placebo-controlled treatment trial of fluoxetine and graded exercise for chronic fatigue syndrome.

BACKGROUND: The Joint Working Group of the Royal Colleges of Physicians, Psychiatrists and General Practitioners (1996) recommended graded exercise and antidepressants for patients with chronic fatigue syndrome. We assessed efficacy and acceptability of these treatments. METHOD: Six-month prospective randomised placebo and therapist contact time controlled trial with allocation to one of four treatment cells: exercise and 20 mg fluoxetine, exercise and placebo drug, appointments only and 20 mg fluoxetine, appointments and placebo drug. Drug treatment was double blind and patients were blind to assignment to exercise or appointments. RESULTS: Ninety-six (71%) of 136 patients completed the trial. Patients were more likely to drop out of exercise than non-exercise treatment (P = 0.05). In an intention to treat analysis, exercise resulted in fewer patients with case level fatigue than appointments only at 26 weeks (12 (18%) v. 4 (6%) respectively P = 0.025) and improvement in functional work capacity at 12 (P = 0.005) and 26 weeks (P = 0.03). Fluoxetine had a significant effect on depression at week 12 only (P = 0.04). Exercise significantly improved health perception (P = 0.012) and fatigue (P = 0.028) at 28 weeks. CONCLUSIONS: Graded exercise produced improvements in functional work capacity and fatigue, while fluoxetine improved depression only.

Adult↗
PubMed1997

Can body composition in multiple organ failure be favorably influenced by feeding?

Multiple organ failure is the final common path of numerous medical conditions whereby the various organ systems fail and are supported by pharmacologic or mechanical means. The patient appears septic but often no septic focus can be found. Whole body protein dynamics are similar to severe sepsis with an elevation of both synthesis and breakdown. Lean body mass is not maintained even in the presence of an apparently adequate energy intake. The more common methods of assessing body composition are all confounded by fluid retention, which also limits parenteral nutrient intake. There are also difficulties with the tolerance of enteral feeding. In the long term, pharmacologic methods are going to be required if it is deemed that the maintenance of body mass is desirable, but in the interim, a robust noninvasive method is required of monitoring body mass in the presence of severe edema.

Body Composition↗
PubMed1997

Assessing the efficacy of nutritional support.

This review outlines the conventional methods of assessing nutritional status and their limitations in the presence of acute trauma and sepsis. It also discusses the problems of attempting to improve or at least maintain nutritional status in the presence of an inflammatory stimulus. Most of the conventional markers of nutritional status are altered in trauma and sepsis with decreases in plasma protein concentrations and muscle strength, an apparent depression of immune function and an increase in extracellular fluid volume. It also appears to be impossible to improve nutritional status in the presence of a severe inflammatory stimulus, and the most one can hope for is to attenuate the rate of decline. The evidence for these observations is discussed.

Biomarkers↗
PubMed1997

Metabolic responses to isoenergetic meals containing different proportions of carbohydrate and fat.

The purpose of the present study was to investigate the interrelationship between carbohydrate and fat metabolism at rest after isoenergetic meals of varying proportions of carbohydrate and fat. Eight physically-active subjects (BMI 18.1-23.4 kg/m2) were studied at rest on three occasions after an overnight fast. In a balanced design they were given meals containing carbohydrate, protein and fat in the following amounts respectively (g/70 kg body weight): meal 1 121, 16, 48; meal 2 70, 16, 70; meal 3 50, 14, 80. All meals were isoenergetic, containing 4.0 MJ/70 kg body weight, and were of similar appearance. In addition, on a fourth occasion five of the eight subjects consumed meal 4 (g/70 kg body weight): carbohydrate 0, protein 0, fat 108. Blood samples were taken before eating the meal and at intervals following the meal to determine metabolic and hormonal responses. Energy expenditure and substrate oxidation were measured by indirect calorimetry and balance was calculated over the 5 h postprandial period. The incremental areas under the time curves for fat oxidation were greatest after meals 3 and 4 (P < 0.05), whereas incremental areas under the carbohydrate oxidation v. time curves were relatively reduced after these two meals (P < 0.05). This was accompanied by lesser suppression of plasma non-esterified fatty acid concentrations (P < 0.001) and reduced plasma insulin concentrations (P < 0.001) following these meals. Energy balance was almost identical after the three isoenergetic meals. In contrast, there was an inverse relationship between carbohydrate and fat balance following these meals, with carbohydrate balance decreasing as carbohydrate intake decreased and fat balance increasing as fat intake increased. We conclude that there is a close interrelationship between carbohydrate and fat metabolism following isoenergetic meals in resting subjects.

Adult↗