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Biomedical subjects

J Coakley

Publications and source records attributed to J Coakley.

At least 19 recordsLinked to original sources
PubMed2006

The absorption of orally supplied beta-alanine and its effect on muscle carnosine synthesis in human vastus lateralis.

Beta-alanine in blood-plasma when administered as A) histidine dipeptides (equivalent to 40 mg . kg(-1) bwt of beta-alanine) in chicken broth, or B) 10, C) 20 and D) 40 mg . kg(-1) bwt beta-alanine (CarnoSyn, NAI, USA), peaked at 428 +/- SE 66, 47 +/- 13, 374 +/- 68 and 833 +/- 43 microM. Concentrations regained baseline at 2 h. Carnosine was not detected in plasma with A) although traces of this and anserine were found in urine. Loss of beta-alanine in urine with B) to D) was <5%. Plasma taurine was increased by beta-alanine ingestion but this did not result in any increased loss via urine. Pharmacodynamics were further investigated with 3 x B) per day given for 15 d. Dietary supplementation with I) 3.2 and II) 6.4 g . d(-1) beta-alanine (as multiple doses of 400 or 800 mg) or III) L-carnosine (isomolar to II) for 4 w resulted in significant increases in muscle carnosine estimated at 42.1, 64.2 and 65.8%.

Adult↗
PubMed2005

Interpretation of alpha-fetoprotein concentrations in cerebrospinal fluid of infants.

BACKGROUND: There are no published reference intervals for concentrations of alpha-fetoprotein (AFP) in the cerebrospinal fluid (CSF) of normal infants. The presence of abnormal concentrations of AFP in plasma or CSF may indicate the presence of a teratoma or a germ cell tumour with yolk sac elements. We measured CSF AFP in infants who did not have malignancy in order to determine its reference intervals. METHODS: AFP was measured in the CSF and/or plasma in 128 infants. Of these, 91 infants had CSF AFP measurements, 94 infants had plasma AFP measurements and in 60 infants AFP concentrations were determined in paired CSF and plasma samples. The patients ranged in age from 1 to 110 days. Both CSF and plasma AFP concentrations were measured by a microparticle enzyme immunoassay using an AxSYM analyser. RESULTS: Using ages corrected for prematurity, the median CSF AFP concentration for babies -69 to 31 days old was 61 kIU/L (5th-95th centile: 2-889 kIU/L), while the median CSF AFP concentration for infants 32 to 110 days was 1.2 kIU/L (5th-95th centile: 0.1-12.5 kIU/L). By age 6 weeks, the concentrations were close to those found in adult plasma and all CSF AFP concentrations from infants with a corrected age over 2 months were <3 kIU/L. CONCLUSION: We have defined reference intervals for CSF AFP concentrations in infants. These results may assist in the diagnosis of CNS tumours, particularly congenital CNS tumours containing yolk sac elements.

Enzyme-Linked Immunosorbent Assay↗
PubMed2001

MFO induction in fish by filtrates from chlorine dioxide bleaching of wood pulp.

Spent bleaching liquors from pulp bleached with chlorine dioxide were assessed for their potency to induce hepatic mixed function oxygenase enzymes (MFO) in rainbow trout, as indicated by activity of ethoxyresorufin-o-deethyase (EROD). Filtrates were collected from two kraft mills in Central Canada to assess the potency of filtrates from hardwood and softwood bleaching. All mill-scale bleaching filtrates induced MFO activity, and filtrates from softwood pulp bleaching appeared more potent than filtrates from hardwood bleaching. Filtrates from the final bleaching stage were most potent, and filtrates from the first stage were the least potent. In laboratory bench-scale bleaching experiments, pulp from softwood and hardwood kraft mills in Eastern Canada was bleached via an industry-standard 5-stage chlorine dioxide bleaching sequence. The filtrates were collected and used in fish bioassays to assess EROD-inducing potency. Potency of bench-scale filtrates varied depending on wood furnish (i.e. softwood vs. hardwood) and the bleaching stage, with all bench-scale filtrates being much weaker EROD inducers than mill-scale filtrates. Recycled paper mill washwater is a possible source of compounds causing increased potency of the mill-scale filtrates.

Animals↗
PubMed2001

Abdominal fat and birth size in healthy prepubertal children.

BACKGROUND: Studies examining the foetal origins hypothesis suggest that small birth size may be a marker of foetal adaptations that programme future propensity to adult disease. We explore the hypothesis that birth size may relate to fat distribution in childhood and that fat distribution may be a link between birth size and adult disease. OBJECTIVE: To investigate the relationship between birth size and abdominal fat, blood pressure, lipids, insulin and insulin:glucose ratio in prepubertal children. DESIGN: Cross-sectional study, based on a birth cohort of consecutive full-term births. SUBJECTS: Two hundred and fifty-five (137 females) healthy, 7- and 8-y-old children. MEASUREMENTS: Body composition and abdominal fat was measured by dual energy X-ray absorptiometry. Lipid, glucose and insulin profiles were measured after an overnight fast and an automated BP monitor was used for blood pressure measurements. RESULTS: There was a negative association between abdominal fat and birth weight s.d. score across a range of normal birth weights (beta=-0.18; 95% CI=-0.31 to -0.04, P=0.009) and a positive association with weight s.d. score at 7/8 y (beta=0.35; 95% CI=0.24 to 0.46, P<0.001). Children who were born with the lowest weight s.d. score and had the greatest weight s.d. score at 7/8 y had significantly more (P<0.001) abdominal fat, as a percentage of total fat (6.53+/-1.3%) than those who had the highest birth weight s.d. score and the lowest weight s.d. score at 7/8 y (4.14+/-0.5%). Similar results were seen if head circumference, but not ponderal index, was used as an indicator of birth size. Increased abdominal fat was associated with higher total cholesterol:HDL cholesterol, higher triglyceride concentration and increased diastolic blood pressure. CONCLUSIONS: Birth weight independently predicted abdominal fat. Children with the highest amount of abdominal fat were those who tended to be born lighter and gained weight centiles. Increased abdominal fat was associated with precursor risk factors for ischaemic heart disease.

Abdomen↗
PubMed1998

Automated analysis of mitochondrial enzymes in cultured skin fibroblasts.

We report automated methods for assaying the activities of the mitochondrial respiratory chain enzyme cytochrome c oxidase (COX), the matrix enzyme citrate synthase (CS), and the cytoplasmic enzyme lactate dehydrogenase (LDH) on a random access analyzer, the Roche Mira S. COX activity was assayed by measuring the initial rate of oxidation of reduced cytochrome c. The CS assay was based on the reaction of this enzyme with oxaloacetate and acetyl-CoA to produce CoASH, which further reacts with dithionitrobenzoic acid producing a free thionitrobenzoate ion. LDH activity was assayed by measuring the reduction of nicotinamide adenine dinucleotide during the oxidation of lactate to pyruvate. Precision of the COX assay was 2. 3%, CS assay 0.7%, and LDH 5.6%. These automated methods were faster by as much as 80%, cheaper by 50%, and used less than half the sample material needed for traditional manual methods. While these assays are often performed by specialized laboratories using dedicated staff, the automated methods presented here are easily performed by staff trained in the regular diagnostic laboratory.

Automation↗
PubMed1998

Suppression of elevated alanine aminotransferase activity in liver disease by vigabatrin.

A patient with hepatic cirrhosis due to Alpers disease is described who had a significantly raised plasma alanine aminotransferase (ALT) activity of 247 U/L which returned to normal (18 U/L) shortly after commencing treatment with the anticonvulsant drug, vigabatrin. Previous studies have reported smaller reductions in plasma ALT activity due to vigabatrin, generally in patients with normal liver function. This case demonstrates that vigabatrin may also reduce markedly elevated ALT activity to the normal range in patients with documented liver disease. Plasma ALT activity cannot be used as an index of liver cell damage in patients receiving vigabatrin.

Alanine Transaminase↗
PubMed1998

Cardiac failure in children with pneumonia in Papua New Guinea.

BACKGROUND: Cardiac failure is suspected of contributing to mortality from pneumonia in children in developing countries, but its role has not been clearly defined. METHODS: A convenience sample of 47 children admitted to Goroka Hospital in Papua New Guinea was studied prospectively with ultrasound, chest radiographs and assays of creatine kinase and lactate dehydrogenase. Results. Seven (15%) of the 47 children died. Of the 43 children who had a chest radiograph, 31 (72%) had severe or very severe pneumonia. No child had poor contractility of the heart on ultrasound examination or unequivocally raised cardiac isoenzymes; therefore no evidence of myocardial injury from sepsis was found. However, ultrasound examination showed dilatation of the right ventricle or hepatic veins in 12 (26%) of the children (both were dilated in 7 children) and 4 (33%) of these children died; this suggests that right ventricular cardiac failure secondary to pulmonary hypertension was present in 26% (95% confidence interval, 14 to 40%) of these children with severe pneumonia. Tachycardia was not associated with right ventricular dilatation on ultrasound, but 3 of the 4 children with more than 3 cm of liver palpable in the abdomen had right ventricular dilatation. Only 4 of the 12 children with right heart failure had hepatomegaly, tachycardia, raised jugular venous pressure or peripheral edema. CONCLUSIONS: Right ventricular failure is common in children with severe pneumonia, and it is probably caused by pulmonary hypertension rather than septic toxemia. The clinical signs of heart failure are unreliable. There is no evidence that digoxin is effective treatment for right ventricular failure secondary to pulmonary hypertension.

Cause of Death↗
PubMed1997

Follow-up services and the development of a clinical nurse specialist in intensive care.

There is little information available regarding quality of life following critical illness. The consequences of a stay in an intensive care unit (ICU) can result in considerable psychological and physical morbidity. At the Homerton Hospital, London, UK an intensive care follow-up outpatient clinic was established to ascertain patients' experiences after discharge from the ICU. This exploratory study examines narrative data collected from 26 patients by means of unstructured client-led interviews. Themes are derived that have implications for staff, patients and relatives. The findings suggest that patients experience a variety of psychological and physical symptoms. Patients experienced vivid dreams, flashbacks, relocation and convalescent stress as well as profound tiredness and weakness. These are consistent with previous research findings. New themes were identified which suggest that mood changes, inability to cope, the need to talk about their ICU experience and indistinct memories of the ICU made recovery at home difficult for both the patients and their families. As a result of these findings, the role of a clinical nurse specialist has developed in order to improve liaison between and within departments, the hospital and the community. Future research will aim to focus on the role of the critical care/community liaison clinical nurse specialist and in improving outcomes through the use of action research.

Adaptation, Psychological↗
PubMed1997

Administration of human recombinant insulin-like growth factor-I in critically ill patients.

OBJECTIVES: To study the pharmacokinetics of a single subcutaneous dose of recombinant human insulin-like growth factor-I (IGF-I) in patients with systemic inflammatory response syndrome in the intensive care unit (ICU). To evaluate the effects of exogenous recombinant human IGF-I on circulating concentrations of IGF-I binding protein-1 (IGFBP-1), IGF-I binding protein-3 (IGFBP-3), and growth hormone in the critically ill patient; to assess the safety of the subcutaneous administration of 40 microg/kg of recombinant human IGF-I in these patients; and to investigate any effect this dose might have on nitrogen balance, creatinine clearance, and serum electrolyte and lipid concentrations. DESIGN: Open-labeled, noncontrolled, prospective, single-dose study of eight fully evaluable ICU patients with systemic inflammatory response syndrome. SETTING: ICUs in a teaching hospital and a linked district general hospital in England. PATIENTS: Nine patients were examined, eight of whom were fully evaluable. INTERVENTIONS: Subcutaneous administration of 40 microg/kg of recombinant human IGF-I. MEASUREMENTS AND MAIN RESULTS: Blood samples were taken 24 hrs before the subcutaneous injection of 40 microg/kg of recombinant human IGF-I, and for 48 hrs thereafter. Urine was collected throughout this period. Serum concentrations of IGF-I, IGFBP-1, IGFBP-3, growth hormone, and insulin were measured by radioimmunoassay. IGF-I concentrations (median and range) increased significantly above baseline values (35 ng/mL [20 to 144]) from 15 mins (p < .02) until 10 hrs (p < .02) after injection of recombinant human IGF-I. Peak IGF-I concentrations were sustained from 2 hrs (90.5 ng/mL [23 to 228]) to 5 hrs (88.5 ng/mL [29 to 300]). By 24 hrs, circulating IGF-I concentrations had returned to baseline values. Baseline IGF-I concentrations were extremely low, and although peak values were three times greater, these values only approached the fifth percentile of defined reference ranges for normal values. Compared with values in less seriously ill patients, maximum IGF-I concentrations were reached earlier, the elimination half-life was shorter, clearance was more rapid, and the apparent volume of distribution was similar. IGFBP-3 concentrations also increased after recombinant human IGF-I injection, and at 3 to 4 hrs were significantly elevated, from 30 mins (p = .04) to 8 hrs (p = .04). There was marked between-patient variability in changes in circulating IGF-I, and IGFBP-1, and IGFBP-3 concentrations. More severely ill patients had the lowest circulating IGF-I concentrations and the least response to exogenous recombinant human IGF-I. Elevated baseline circulating growth hormone concentrations (2.3 ng/mL, range 0.8 to 4 [5.1 mU/L, 1.5 to 8]) were significantly depressed from 4 hrs (0.5 ng/mL, 0.5 to 1.5 [1 mU/L, 1 to 3], p = .01) to 6 hrs (0.8 ng/mL, 0.5 to 4 [1.5 mU/L, 1 to 8], p = .02) after recombinant human IGF-I administration. CONCLUSION: We observed no adverse effects (e.g., hypoglycemia) that could be attributed to recombinant human IGF-I therapy.

Adult↗
PubMed1997

Plasma and serum micronutrient concentrations in preschool children.

The plasma concentrations of vitamin A, vitamin E, beta-carotene and serum concentrations of zinc, retinol-binding protein and prealbumin were examined for a random cluster sample, stratified by socioeconomic status, of 467 healthy preschool children. Children were aged 9-62 months; 44% were females. The mean plasma values were: vitamin A, 1.29 micromol l(-1); vitamin E, 18.9 micromol l(-1); and beta-carotene, 0.30 micromol l(-1). The mean serum values were: zinc, 13.9 micromol l(-1); retinol-binding protein, 25.5 mg l(-1); and prealbumin, 186.2 mg l(-1). The mean molar ratio of vitamin A to retinol-binding protein for the study group was 1.10. There were no differences in the mean values of any of the measured micronutrients between the genders. The results of this survey do not indicate that the prevalence of micronutrient deficiency in this preschool population is of public health significance.

Antioxidants↗
PubMed1997

Age-specific reference intervals for plasma vitamins A, E and beta-carotene and for serum zinc, retinol-binding protein and prealbumin for Sydney children aged 9-62 months.

Paediatric reference intervals for blood concentrations of certain nutrients are often based on either adult data or are derived from small samples of young children. Biochemical data were obtained from 467 randomly selected, healthy preschool children aged 9-62 months in Sydney, Australia. Data were obtained for plasma vitamins A, E and beta-carotene and for serum zinc, retinol-binding protein and prealbumin. Reference intervals based on the 2.5 and 97.5 centiles for age groups 9-23, 24-35, 36-47, 48-62 months and for the total group (9-62 months) were calculated. The 2.5-97.5 centiles for the whole group were: vitamin A, 0.7-1.8 mumol/l (20.05-51.56 micrograms/dl); vitamin E, 8-30 mumol/l (0.34-1.29 mg/dl); beta-carotene, 0.1-1.1 mumol/l (5.4-59.0 micrograms/dl); zinc, 9-19 mumol/l (58.8-124.2 micrograms/dl); retinol-binding protein, 14-36 mg/l; prealbumin, 104-264 mg/l. The reference intervals reported are consistent with the findings of a number of smaller studies and are likely to be an accurate reflection of the true intervals for healthy preschool children in western developed countries.

Aging↗
PubMed1996

Should ICU patients receive muscle relaxants?

Neuromuscular blocking agents (NMBAs) are used in many critically ill patients, although their use is declining. NMBAs are designed for short term use in the operating theatre, and there are few studies in the critical care setting of either efficacy or safety, in particular their metabolism may be impaired by organ dysfunction. Weakness associated with critical illness is multifactorial, but in many cases is associated with myopathies and neuropathies. The possible role of NMBAs in the development of weakness is unclear, but there is no proven link between the use of NMBAs and neuropathy or myopathy.

Atracurium↗
PubMed1994

Respiratory effort perception at rest and during carbon dioxide rebreathing in patients with dystrophia myotonica.

BACKGROUND: Breathlessness appears to be closely related to the perception of the outgoing motor command to breathe and should be increased in the presence of muscle weakness. However, breathlessness is not a common symptom in patients with chronic muscle disease who have weak respiratory muscles. The factors that determine the perception of respiratory effort in such patients have not been examined. METHODS: The inspiratory effort sensation during resting breathing and progressive hypercapnia was investigated in 12 patients with dystrophia myotonica with weak respiratory muscles (nine men and three women of mean (SD) age 41.1 (10.5) years; maximum inspiratory pressure 43.1 (17.2) cm H2O) and an age and sex matched control group of normal subjects of mean age 39.6 (10.6) years and a maximum inspiratory pressure of 123 (15.2) cm H2O. RESULTS: During resting breathing with a mouthpiece no differences were seen in inspiratory effort sensation, mouth occlusion pressure, or tidal volume, but inspiratory time and cycle duration were significantly shorter in the patients with dystrophia. Minute ventilation (VE) was significantly higher in the patients (15.8 (4.0) l/min v 12.5 (2.6) l/min), while resting breathing was no more variable in the patients than in controls. The ventilatory response to carbon dioxide (VE/PCO2) was not significantly lower in the patients (14.9 (6.9) l/min/kPa) than in the controls (17.4 (4.3) l/min/kPa). Effort sensation responses to carbon dioxide driven breathing were similar in the control subjects and the patients. With regression analysis of pooled data neither maximum inspiratory pressure nor disease state contributed to perceived inspiratory effort during hypercapnia. CONCLUSIONS: Moderately severe global respiratory muscle weakness does not appear to influence the ventilatory response to rising carbon dioxide tension or the perception of inspiratory effort in patients with dystrophia myotonica.

Adult↗