Biomedical subjects

J L Murphy

Publications and source records attributed to J L Murphy.

At least 19 recordsLinked to original sources

PubMed2002

Influence of glucose ingestion by humans during recovery from exercise on substrate utilisation during subsequent exercise in a warm environment.

Carbohydrate (CHO) ingestion during short-term recovery from prolonged running has been shown to increase the capacity for subsequent exercise in a warm environment. The aim of this study was to examine the effects of the amount of glucose given during recovery on substrate storage and utilisation during recovery and subsequent exercise in a warm environment. A group of 11 healthy male volunteers took part in two experiments in a controlled warm environment (35 degrees C, 40% relative humidity), 1 week apart. On each occasion the subjects completed two treadmill runs (T1 and T2) at a speed equivalent to 60% of maximal oxygen uptake, for 90 min, until they were fatigued, or until aural temperature (T(aur)) reached 39 degrees C. The two runs were separated by a 4 h recovery period (REC), during which subjects consumed 55 g of naturally enriched [U-(13)C]-glucose in the form of a 7.5% carbohydrate-electrolyte solution (CES, mass of solution 667 g) immediately after T1. The subjects then consumed either: the same quantity of CES, or an equivalent volume of an electrolyte placebo, at 60, 120 and 180 min during REC, providing a total of 220 g (C220) or 55 g (C55) of [U-(13)C]-glucose, respectively. Expired gases were collected at 15 min intervals during exercise and 60 min intervals during REC, for determination of total CHO and fat oxidation by indirect respiratory calorimetry, and orally ingested [U-(13)C]-glucose oxidation, estimated from the (13)C:(12)C ratio of expired CO(2). Substrate metabolism did not differ between conditions during T1. Despite the fact that total CHO (P < 0.05) and ingested glucose oxidation (P < 0.01) were greater during REC of the C220 condition, glycogen synthesis was estimated to be approximately fivefold greater (P < 0.01) than in the C55 condition. During T2 the rate of total CHO oxidation was higher (P < 0.01) and total fat oxidation lower (P < 0.01) at all times during the C220 compared to the C55 condition. The greater CHO oxidation during C220 appeared to be met from ingested sources, as the rate of [U-(13)C]-glucose oxidation was greater (P < 0.01) at all times during T2, compared to C55. Whilst more of the ingested substrate remained unoxidised on completion of T2 during C220, exercise duration was similar in the two experimental conditions, and was limited by thermoregulatory incapacity (T(aur) > 39 degrees C) rather than substrate availability per se.

Administration, Oral↗

PubMed2002

Maldigestion and malabsorption of dietary lipid during severe childhood malnutrition.

BACKGROUND: Diets rich in lipid are used to provide energy density in treating children with severe malnutrition, but the extent to which their digestion and absorption can cope with the load effectively is uncertain. AIM: To determine the extent of impaired digestion or absorption, in three groups of eight malnourished children (aged 5-23 months) using isotopic probes of the predominant fatty acids in coconut and corn oil used to fortify the diet. METHODS: Each child received oral doses of one of three (13)C labelled triglycerides (trilaurin, triolein, or trilinolein). The recovery of (13)C label in stool either as triglyceride (TAG) or fatty acid (FA), was used to assess digestion and absorption. In a separate test, the recovery of label in stool following an oral dose of [(13)C]-glycocholate was measured to assess bile salt malabsorption. RESULTS: The median recovery of label in stool was 9% (range 1-29%) of administered dose. Following treatment there was a reduction in stool (13)C excretion for the labelled TAG (<1%). In half the subjects, label was recovered as TAG in stool (median 0.6%, range 0-44%). Most label in stool was recovered as FA (median 30%, range 0-100%). Following [(13)C]-glycocholate, label was recovered in excess in about one third of studies. CONCLUSION: Abnormalities in the gastrointestinal handling of lipid were observed in over 50% of children with severe malnutrition, reflecting problems in absorption, although impaired solubilisation or hydrolysis could also be contributory factors. The underlying lesion improves as treatment progresses, leading to concomitant improvement in function.

Carbon Isotopes↗

PubMed2001

Exogenous carbohydrate oxidation from drinks ingested during prolonged exercise in a cold environment in humans.

Six healthy male volunteers performed four rides to exhaustion on a cycle ergometer at approximately 80% of maximal oxygen consumption. Subjects ingested a bolus volume of fluid (7.14 ml/kg) immediately before exercise and additional fluid volumes (1.43 ml/kg) every 10 min during exercise. The fluids ingested were either a flavored water control or glucose-electrolyte beverages with glucose concentrations of 2, 6, or 12%. The beverages were labeled with [U-(13)C]glucose (99.2%: 0.05 g/l). Exercise capacity was not different (P = 0.13) between trials; median (range) exercise time was 83.52 (79.85--89.68), 103.19 (78.82--108.22), 100.37 (80.60--124.07), and 94.76 (76.78--114.25) min in the 0, 2, 6, and 12% trials, respectively. The oxidation of exogenous glucose in each 15-min period was significantly lower in the 2% trial (P = 0.02) than in the 6 and 12% trials where oxidation rates were between 0.5 and 0.7 g/min. No difference in endogenous glucose oxidation was observed between trials (P = 0.71). These findings indicate that the oxidation of exogenous glucose during exercise of this intensity and duration in a cold environment is similar to that observed in warmer conditions. Thus a low oxidation of exogenous substrate is unlikely to be a factor limiting the effectiveness of carbohydrate-electrolyte drink ingestion on exercise capacity in a cold environment.

Acclimatization↗

PubMed2001

Gastrointestinal handling and metabolic disposal of 13C-labelled tripalmitin during rehabilitation from childhood malnutrition.

We investigated the gastrointestinal handling and post-absorptive metabolic handling of [1,1,1-13C]tripalmitin and [1-13C]glycocholate during recovery from severe childhood malnutrition. Eight children were studied on three occasions: at admission (phase 1), during rapid catch-up growth (phase 2) and when weight-for-height had reached 90 % of the reference (phase 3). Breath samples were obtained over a 24 h period and stools were collected over 3 d following the administration of each tracer. At admission, the lipid content of stool expressed as a percentage of ingested lipid was 6 (range 0.7-28.9) but less variation was shown between children at phase 2 (3.3 (range 0.9-4.1)) and phase 3 (1.4 (range 0.4-2.5)). The excretion of 13C in stool varied markedly between children at admission (11.1 (sd 5.4) % administered dose) and during rehabilitation (phase 2, 15.4 (sd 16.5) % administered dose; phase 3, 6.2 (sd 10.2) % administered dose). About 5 % of the absorbed label was recovered on breath at each stage (% absorbed dose; phase 1, 5.1 (sd 6.0); phase 2, 5.2 (sd 3.1); phase 3, 6.4 (sd 6.6)). None of the children exhibited significant bile salt malabsorption as a consequence of small intestinal overgrowth. Of the 13C measured in stool, more label was recovered in fatty acids than triacylglycerols during each of the three phases and this was interpreted to reflect a failure to absorb the products of digestion. The results show that not all the children had problems associated with the digestion and absorption of 13C-labelled tripalmitin in severe malnutrition and during recovery, which was not reflected in gross lipid balance across the gastrointestinal tract. Absorbed lipid was more likely to be deposited as adipose tissue than to satisfy the immediate needs for energy.

Adolescent↗

PubMed1999

Effect of fatty acid chain length and saturation on the gastrointestinal handling and metabolic disposal of dietary fatty acids in women.

The gastrointestinal handling and metabolic disposal of [1-13C]palmitic acid, [1-13C]stearic acid and [1-13C]oleic acid administered within a lipid-casein-glucose-sucrose emulsion were examined in normal healthy women by determining both the amount and nature of the 13C label in stool and label excreted on breath as 13CO2. The greatest excretion of 13C label in stool was in the stearic acid trial (9.2% of administered dose) whilst comparatively little label was observed in stool in either the palmitic acid (1.2% of administered dose) or oleic acid (1.9% of administered dose) trials. In both the palmitic acid and oleic acid trials, all of the label in stool was identified as being present in the form in which it was administered (i.e. [13C]palmitic acid in the palmitic acid trial and [13C]oleic acid in the oleic acid trial). In contrast, only 87% of the label in the stool in the stearic acid trial was identified as [13C]stearic acid, the remainder was identified as [13C]palmitic acid which may reflect chain shortening of [1-13C]stearic acid within the gastrointestinal tract. Small, but statistically significant, differences were observed in the time course of recovery of 13C label on breath over the initial 9 h of the study period (oleic acid = palmitic acid > stearic acid). However, when calculated over the 24 h study period, the recovery of the label as 13CO2 was similar in all three trials (approximately 25% of absorbed dose). These results support the view that chain length and degree of unsaturation may influence the gastrointestinal handling and immediate metabolic disposal of these fatty acids even when presented within an emulsion.

Adult↗

PubMed1999

Metabolism of lactose-[13C]ureide and lactose-[15N,15N]ureide in normal adults consuming a diet marginally adequate in protein.

Oral lactose-ureide is resistant to human digestive enzymes, but is fermented by the colonic microflora. Nine normal adults consuming a diet which provided 36 g of protein/day were given oral doses of lactose-[(13)C]ureide and lactose-[(15)N,(15)N]ureide. The appearance on breath of (13)CO(2) derived from lactose-[(13)C]ureide was followed for 48 h. The fate of (15)N derived from lactose-[(15)N, (15)N]ureide was determined by measuring the recovery of (15)N in stools and urine in various forms. About 80% of the label given as lactose-[(13)C]ureide was recovered on the breath, and about 80% of label given as lactose-[(15)N,(15)N]ureide was not recovered in stool, indicating that 80% of the dose was completely fermented. At least 5% of the labelled urea was absorbed and excreted as the intact molecule. Of the (15)N derived from lactose-[(15)N, (15)N]ureide and available for further metabolic interaction, 67% was retained and 33% was excreted in urine. The time taken for [(15)N,(15)N]urea to appear in urine was similar for all subjects, but the appearance of either (13)CO(2) on the breath or [(15)N, (14)N]urea in urine varied. It is concluded that the hydrolysis of the sugar-urea bond may reflect oro-caecal transit time, but that other factors related to colonic bacterial metabolism determine the duration and extent of hydrolysis of urea by urease enzymes. Lactose-ureide can be used to probe the metabolic activity of the colonic microflora in normal individuals.

Adult↗

PubMed1998

The effect of age and gender on the metabolic disposal of [1-13C] palmitic acid.

OBJECTIVE: To examine the effect of age and gender on the metabolic disposal of [1-13C]palmitic acid. DESIGN: Cross-sectional. SETTING: Clinical Nutrition and Metabolism Unit at Southampton General Hospital, Institute of Human Nutrition, University of Southampton. SUBJECTS AND MEASUREMENTS: Twelve children (5 boys and 7 girls; aged 5-10 y) and six men (BMI 23.3 +/- 2.6 kg/m2; aged 20-30 y) were recruited. Following oral administration of a bolus dose of [1-13C]palmitic acid (10 mg/kg body weight) consumed with a test meal (1667 kJ) the excretion of 13C-label was measured on breath as 13CO2 over 24 h and in stool over 5 d to account for differences in absorption of [1-13C]palmitic acid. The 13C-enrichment of samples was determined by continuous flow-isotope ratio mass spectrometry. Net substrate oxidation was estimated from gaseous exchange measurements in the postabsorptive state and over 6 h postprandially. RESULTS: The excretion of 13CO2 on breath varied between subjects both in the pattern and amount excreted over 24 h. Breath 13CO2 was not different between boys (61.0 +/- 22.4% of absorbed dose) and girls (54.2 +/- 17.9% of absorbed dose). The excretion of breath 13CO2 was less in the men (35.1 +/- 9.3% of absorbed dose; P = 0.005) and that observed previously by our group in women (30.7 +/- 6.7% of absorbed dose; P = 0.005) than in the children. Net fat oxidation was greater in the children in both the postabsorptive (2.43 +/- 0.78 g/h) and postprandial (11.89 +/- 3.13 g/6 h) states than in the men (0.93 g/h +/- 1.50; P = 0.016; 9.86 +/- 10.53 g/6 h; NS) and women studied previously (0.53 +/- 0.68 g/h; P = 0.003; 0.03 +/- 3.21 g/6 h; P = 0.001). CONCLUSIONS: Our observations that children oxidised nearly twice the amount of [1-13C]palmitic acid than adults in conjunction with greater net fat oxidation in children than adults in both the postabsorptive and postprandial states should be considered before current UK dietary recommendations for fat and saturated fats, developed for adults, are applied to growing children. For dietary recommendations to be developed further more information is required, particularly in groups of infants and the elderly, about the factors that influence the postprandial handling of dietary fat.

Absorption↗

PubMed1998

Metabolic handling of 13C labelled tripalmitin in healthy controls and patients with cystic fibrosis.

AIM: To examine the gastrointestinal handling and metabolic disposal of emulsified [1-13C]palmitic acid esterified into a triglyceride in nine healthy children and seven patients with cystic fibrosis on enzyme replacement treatment. METHODS: After an overnight fast, each child was given 10 mg/kg body weight [1,1,1-13C]tripalmitin with a standardised test meal of low natural 13C abundance. The total enrichment of 13C was measured using isotope ratio mass spectrometry in stool collected for a period of up to five days and in breath samples collected over a 24 hour period. RESULTS: The mean proportion of administered 13C label excreted in stool was 6% (range, 1-12.7%) in healthy children and 24.6% (range, 0-64%) in patients with cystic fibrosis. Healthy children excreted 31.3% of the administered label on their breath (range, 14.2-42.9%). Correcting the excretion of administered 13C label on the breath for differences in digestion and absorption in patients with cystic fibrosis increased the difference between individuals from 0-31.3% of administered dose (mean, 17.9%) to 0-49.1% of absorbed dose (mean, 23.2%) and was poorly related to the amount of 13C label in stool. CONCLUSION: Measurements of breath 13CO2 do not consistently reflect the gastrointestinal handling of emulsified 13C labelled tripalmitin because of differences in digestion and absorption in cystic fibrosis. Further studies need to examine whether "breath tests" alone can predict with confidence the gastrointestinal handling of other 13C labelled triglycerides and fatty acids.

Breath Tests↗

PubMed1997

The effects of cysteamine on the upper gastrointestinal tract of children with cystinosis.

The purpose of this study was to evaluate the effects of cysteamine on gastric acid output and serum gastrin levels in children with nephropathic cystinosis. We studied four children with nephropathic cystinosis receiving a dose of free base cysteamine of 14.35 mg/kg four times a day (range 12.30-18.80 mg/kg). Gastric acid was measured for the hour before and after administration of the medication. Serum gastrin levels were obtained at 0, 30, 60, and 90 min following the medication. Gastrointestinal anatomy was evaluated by endoscopy and biopsy. Following administration of the medication, all subjects showed an increase in gastric acid output. Mean acid output increased from 0.79 to 2.22 mEq/h. Mean gastric acid output adjusted for body weight increased from 0.03 to 0.09 mEq/kg per hour. Following administration of the medication, all subjects showed an increase in serum gastrin. The mean increase above the base value was 38.3 pg/dl. Two of the four subjects demonstrated visual and histological evidence of inflammation. Cysteamine has a marked effect on gastric acid production and serum gastrin, even at the dose used in children with nephropathic cystinosis. The clinical effect of this acid production is unknown but may be significant.

Adolescent↗

PubMed1997

Stable-isotope method for determining the gastrointestinal handling of [1-13C]palmitic acid.

The 13C enrichment in individual fatty acids extracted from human feces following the oral administration of [1-13C]palmitic acid has been determined using a novel approach based upon gas chromatography-isotope ratio mass spectrometry. The method was established and tested for precision and repeatability. Analytical precision was determined from 10 repeated injections of a sample containing 16:0 and 18:0 with levels of delta 13C abundance measured at -34.01 +/- 0.60 and -23.62 +/- 0.95 delta per mil (parts per thousand) (/1000), respectively (mean +/- SD). For the repeatability study, measurement of enrichment of the same mixture of unlabeled fatty acid methyl ester (FAME) standards (13:0, 14:0, 16:0, and 18:0) was found to have standard deviations (0.45, 0.56, 1.46 and 1.54/1000, respectively). When labeled [1-13C]palmitic acid was serially diluted with naturally enriched palmitic acid, a linear relationship was obtained to a dilution of 10% enriched compound (530/1000). FAME were prepared from two fecal samples from a normal healthy adult; the first, a baseline specimen, containing no added label and the second, followed a single oral dose of [1-13C]palmitic acid and was enriched. Enrichment in 13C was confined to the solvent-soluble fraction following lipid extraction, and was only identified with prior acidification. The enrichments were measured in triplicate, baseline sample -32.66 +/- 0.5/1000, enriched sample +268.61 +/- 8.0/1000. Enrichment was restricted to the labeled species consumed, 16:0. The methodology described here allows for the separation of compounds prior to the determination of enrichment and can be utilized to contribute to a more complete description of the gastrointestinal handling of labeled substrates than previously obtained.

Carbon Isotopes↗

PubMed1997

Gastrointestinal handling of [1-13C]palmitic acid in healthy controls and patients with cystic fibrosis.

AIM: To examine the gastrointestinal handling of [1-13C]palmitic acid given as the free acid by measuring the excretion of 13C label in stool in 16 healthy children and 11 patients with cystic fibrosis on their habitual enzyme replacement treatment. METHODS: After an overnight fast, each child ingested 10 mg/kg body weight [1-13C]palmitic acid with a standardised test meal of low natural 13C abundance. A stool sample was collected before the test and all stools were collected thereafter for a period of up to five days. The total enrichment of 13C in stool and the species bearing the 13C label was measured using isotope ratio mass spectrometry. RESULTS: The proportion of administered 13C label excreted in stool was 24.0% (range 10.7-64.9%) in healthy children and only 4.4% (range 1.2-11.6%) in cystic fibrosis patients. The enrichment of 13C in stool was primarily restricted to the species consumed by the subjects (that is as palmitic acid). CONCLUSIONS: There does not appear to be a specific defect in the absorption of [1-13C]palmitic acid in patients with cystic fibrosis. The reasons why cystic fibrosis patients appear to absorb more of this saturated fatty acid than healthy children is not clear and requires further investigation.

Adolescent↗

PubMed1995

The gastrointestinal handling and metabolism of [1-13C]palmitic acid in healthy women.

The gastrointestinal handling and metabolism of [1-13C]palmitic acid given as the free fatty acid was examined in six healthy women by measuring the excretion of 13C-label in stool and in breath as 13CO2. The gastrointestinal handling of [1-13C]palmitic acid was compared with the apparent absorption of dietary lipid by measuring lipid losses in stool. The variation both within and between subjects was determined by repeating the study in the same individuals on separate occasions. The time course for excretion of label in stool over the five-day study period followed a common pattern, with most of the label excreted over the first two days of the stool collection. 13C-Label excreted in stool over the five-day study period was 14.3 +/- 9.8% of that administered and on repeating the trial was 31.6 +/- 24.7% (not significantly different due to variability); there was poor agreement within subjects. Lipid excreted in stool expressed as a percentage of ingested lipid was 5.2 +/- 4.4% in Trial 1 and 5.9 +/- 4.0% in Trial 2, and was the same in each individual on repeating the trial. There was no clear relationship between the excretion of 13C-label and lipid in stool (Trial 1: R = -0.43, P > 0.40; Trial 2: R = -0.02, P > 0.97). On the first occasion, 22.0 +/- 4.5% of the administered label was excreted on breath over the 15-h study period and on repeating the trial was 15.8 +/- 9.5% (not significantly different) with poor repeatability in a given individual.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Faecal interleukin-8 and tumour necrosis factor-alpha concentrations in cystic fibrosis.

Interleukin-8 (IL-8) and tumour necrosis factor-alpha (TNF-alpha) concentrations were measured in faecal samples from nine patients with cystic fibrosis and nine healthy age matched controls. The patients were assessed with Shwachman score, apparent energy absorption, pancreatic enzyme dosage, simple spirometry, and presence of pseudomonal colonisation. Median (range) wet stool IL-8 and TNF-alpha concentrations in patients were 32,113 pg/g (21,656-178,128) and 3187 pg/g (368-17,611) respectively, compared with < 43.5 pg (IL-8)/g (< 22-4079) and 99 pg (TNF-alpha)/g (< 0.26-231) in controls. IL-8 concentration was negatively correlated with Shwachman score (r = -0.79) and pancreatic enzyme dosage (r = -0.77), but not with energy absorption. Seven patients were mature enough to cooperate with spirometry. Their IL-8 concentrations correlated with percentage predicted forced expiratory volume in one second (r = -0.78). IL-8 concentration was greater in four patients with, than five without, established pseudomonal colonisation: median difference 134,583 pg/g. TNF-alpha concentration was not correlated with measures of disease severity. Faecal IL-8 concentration might reflect the severity of pulmonary inflammation in cystic fibrosis and could provide an easily obtainable marker of disease activity.

Adolescent↗

PubMed1994

Strategies for designing culturally relevant client education materials.

This article addresses strategies for designing and implementing a culturally significant and appropriate client education tool for use with non-English-speaking clients or for any client in a culture different from the mainstream. These strategies include: (1) understanding the relationship between culture and behavior, (2) developing a strategic plan, (3) gathering demographic data about the setting, (4) evaluating the characteristics of the learner, and (5) developing culturally specific, unique education learning materials.

Communication Barriers↗

PubMed1993

Fatal Pneumocystis pneumonia in a child treated for focal segmental glomerulosclerosis.

A 4-year-old female with nephrotic syndrome secondary to focal segmental glomerulosclerosis (FSGS) was treated with pulse methylprednisolone and chlorambucil therapy. She subsequently developed fatal Pneumocystis carinii pneumonia (PCP). This is the first report of a pediatric patient whose treatment for FSGS resulted in PCP, raising the issue of PCP prophylaxis for these patients.

Child, Preschool↗

PubMed1993

Hypercholesterolemia in children with cystinosis.

Ten children with cystinosis had their diet, serum creatinine, and total cholesterol (averaged in 6-month blocks and normalized by calculating a z score (TCz)] monitored for a mean of 5 years. The TCz scores were elevated in boys (P < 0.01) but not girls (P = 0.67). The boys had elevated TCz scores for 58% of their 29 pre-transplantation years of follow-up, rising as early as 1 year of age at a mean rate of 0.67 standard deviations per year. Cystinotic boys had higher TCz scores than children with other tubular disorders (P < 0.025). All 4 cystinotic boys who developed renal insufficiency had a rise in TCz scores at a rate greater than control children with comparable renal impairment. Two cystinotic boys received a renal transplant; subsequent TCz scores were markedly lower, but remained elevated. The nutritional status of cystinotic children deteriorates after 3 years of age: they have decreased fat stores, elevated TCz scores and consume high fat diets insufficient in total calories. In summary, cystinotic boys have marked, progressive hypercholesterolemia which improves after renal transplantation.

Child↗

PubMed1993

Hypertension and pulmonary oedema associated with ketamine administration in a patient with a history of substance abuse.

Cocaine use, frequently associated with other substance abuse, is becoming more common in the pregnant patient. These patients are more likely to experience peripartum complications. A case of hypertension and pulmonary oedema in such a patient, possibly triggered by ketamine, is reported. A tumultuous course in the intensive care unit was resolved when the patient's hypertension and sympathetic reactivity were successfully treated with barbiturates. A number of factors supported a diagnosis of barbiturate withdrawal in this patient, its onset also was related temporally to ketamine administration. Hypertension should be considered a sign of acute barbiturate withdrawal. If a history of cocaine use, particularly crack cocaine, is elicited, one should suspect multiple substance abuse and be especially cautious when administering ketamine.

Adult↗

PubMed1993

Variability of fecal energy content measured in healthy women.

The variability of daily stool energy losses was examined in six healthy adult women over a complete menstrual cycle. On average, stool energy was 0.74 +/- 0.15 kJ/d (mean +/- SD) for the group. For a given individual, daily stool energy varied up to twofold. The variability for rolling averages of daily fecal energy losses over 3-, 5-, and 7-d periods showed no significant differences between collection periods of 3 and 5 d and 5 and 7 d. There was a close linear relationship between the energy content of the stool and either the wet or dry weight of stool (range 17-460 g wet wt). In metabolic studies of healthy women representative values for daily losses of energy in stool can be obtained from a 3-d collection. The energy content of wet stool was approximately 7 kJ/g. Under field conditions, weighing the stool provides a simple, useful method of assessing fecal energy losses.

Adult↗