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Biomedical subjects

J L Murphy

Publications and source records attributed to J L Murphy.

At least 19 recordsLinked to original sources
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↗
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↗
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↗
PubMed1992

Adaptation to a diet low in protein: effect of complex carbohydrate upon urea kinetics in normal man.

1. Urea kinetics were measured by using prime/intermittent oral doses of [15N15N]urea in five healthy men taking formula diets adequate in energy and containing either 70 or 35 g of protein/day. In some studies the low-protein diet was supplemented with non-starch polysaccharides in the form of ispaghula husk or ripe bananas. 2. On the 70 g of protein/day diet urea production was 132% of intake. Only 54% of the urea produced was excreted in the urine with 46% being salvaged in the colon; 90% of the salvaged nitrogen was retained in the metabolic nitrogen pool. 3. On the 35 g of protein/day diet the small decrease in urea production rate compared with that on the 70 g of protein/day diet was not significant, but only 36% of the urea produced was excreted in urine, with the majority, 64%, being salvaged. 4. The extent of urea-nitrogen salvaging on the 35 g of protein/day diet was similar in magnitude to the decrease in nitrogen intake, with the effect that the sum of intake and salvaged nitrogen did not differ between the 35 and the 70 g of protein/day diets. This implies that quantitative control is exerted over the rate at which urea nitrogen is salvaged. 5. The addition of non-starch polysaccharides to the 35 g of protein/day diet had a demonstrable effect upon faecal weight and composition, but did not exert any significant influence upon urea kinetics.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed1992

Renal tubular acidosis in children treated with trimethoprim-sulfamethoxazole during therapy for acute lymphoid leukemia.

The antibiotics trimethoprim (TMP) and sulfamethoxazole (SMZ), when used in combination, can cause metabolic acidosis, renal bicarbonate wasting, and growth failure. Retrospective review of repeated random serum chemistries from 10 children receiving TMP-SMZ and maintenance chemotherapy for acute lymphoid leukemia revealed low serum bicarbonate (P = .0002) and elevated serum chloride (P less than .0005) concentrations. These values normalized after all medications were discontinued. Prospective study of 8 children receiving TMP-SMZ and chemotherapy for acute lymphoid leukemia revealed lower serum bicarbonate concentrations and higher urine pH following a dose of TMP-SMZ than paired values obtained more than 3 days after a dose. Four children (50%) met serum bicarbonate and urinary pH criteria for the diagnosis of renal tubular acidosis soon after a dose of TMP-SMZ. The occurrence of TMP-SMZ-induced renal tubular acidosis has implications for the acid-base balance of children receiving TMP-SMZ on a long-term basis.

Acidosis, Renal Tubular↗
PubMed1991

Energy content of stools in normal healthy controls and patients with cystic fibrosis.

Stool energy losses and the sources of energy within the stool were determined in 20 healthy controls and 20 patients with cystic fibrosis while on their habitual pancreatic enzyme replacement treatment. Stool energy losses were equivalent to 3.5% of gross energy intake in healthy children (range 1.3-5.8%). Despite a comparable gross energy intake, stool energy losses were three times greater in patients with cystic fibrosis than controls averaging 10.6% of gross energy intake (range 4.9-19.7%). Stool lipid could account for only 29% and 41% of the energy within the stool in controls and patients with cystic fibrosis respectively and was poorly related to stool energy. Approximately 30% of the energy within the stool could be attributable to colonic bacteria in both the healthy children and patients with cystic fibrosis. These results suggest that stool energy losses in healthy children are relatively modest but that even when patients with cystic fibrosis are symptomatically well controlled on pancreatic enzyme replacement, raised stool energy losses may continue to contribute towards an energy deficit sufficient to limit growth in cystic fibrosis. As the energy content per gram wet weight remains relatively constant (8 kJ/g), stool energy losses may be estimated from simple measurements of stool wet weight.

Adolescent↗
PubMed1991

Lymphatic fistula after vascular reconstruction: a case-control study.

A retrospective case-control study was carried out to assess the importance of lymphatic fistulas that develop after vascular reconstruction and to determine the risk factors associated with them. The authors compared 35 patients who had lymphatic fistula after vascular reconstruction with 70 control patients, taken from the same database. They found a significant difference between the two groups only in age and indication for surgery: lymphatic fistulas were more likely to develop in older patients and in patients who underwent aortobifemoral bypass for limb salvage rather than for claudication (p less than 0.05).

Aged↗