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Biomedical subjects

A Pettigrew

Publications and source records attributed to A Pettigrew.

At least 19 recordsLinked to original sources
PubMed1997

Alterations in dopamine clearance and catechol-O-methyltransferase activity by dopamine infusions in children.

OBJECTIVE: To determine the role of catechol-O-methyltransferase (COMT) in the biodisposition of pharmacologic concentrations of dopamine. DESIGN: The study was an open-label dose escalation trial in which dopamine was employed as the sole exogenous catecholamine. The dosage was adjusted to achieve improvements in cardiac output or to augment renal function. SETTING: A 16-bed pediatric intensive care unit serving both medical and surgical patients. PATIENTS: The study was performed using 14 dopamine-treated and five untreated control patients. Children ranged in age from 16 days to 12 yrs; five of the treated patients and two of the untreated controls were female. All but one of the study patients were enrolled within 24 hrs of palliative or corrective surgery for congenital heart disease. Control patients had noncardiac surgical procedures. Both treated and control groups were similar with respect to severity of illness, as judged by Therapeutic Intervention Scoring System score. INTERVENTIONS: All treated patients received dopamine as a continuous intravenous infusion. Infusion rates were determined by caregivers and ranged from 3.0 to 20 micrograms/kg/min. MEASUREMENTS AND MAIN RESULTS: Serial, timed blood samples were obtained from patients and control subjects for the determination of plasma dopamine concentrations and for the determination of mononuclear cell COMT activity. Measured rates of dopamine infusion (3.0 to 18.3 micrograms/kg/min) were consistently less than the nominal rates (3.0 to 20.0 micrograms/kg/min) of infusion (p < .0001) due in part to calculations based on the hydrochloride salt rather than dopamine base. At similar steady-state infusion rates, plasma dopamine concentrations varied over a four-fold range, with steady-state concentrations at even the lowest infusion rate exceeding endogenous concentrations by at least ten-fold. Variations in steady-state plasma dopamine concentration reflected large age-associated variations in dopamine clearance, which was found to be saturable at concentrations of > 200 ng/mL. Mononuclear cell COMT activity was assessed simultaneously in these patients. Baseline COMT activity varied over a six-fold range and was unrelated to dopamine clearance or patient age. COMT activity increased two- to six-fold in dopamine-treated patients with plasma steady-state dopamine concentrations of > 100 ng/mL. CONCLUSIONS: These data demonstrate marked age and concentration-dependent differences in dopamine clearance that account for large interindividual differences in the steady-state plasma dopamine concentrations in patients receiving similar infusion rates. While concomitant variability in COMT activity is observed, the lack of correlation between dopamine clearance and COMT activity suggests that COMT is not rate-limiting for the clearance of exogenously administered dopamine.

Catechol O-Methyltransferase↗
PubMed1992

Application of an organic solvent extraction to the determination of catechol-O-methyltransferase activity by high-performance liquid chromatography in human mononuclear cells.

We report here a method for measuring mononuclear cell catechol-O-methyltransferase (COMT) activity which is ideally adapted to clinical studies. The method measures the O-methylation of dopamine to 3-methoxytyramine and 4-methoxy-3-hydroxyphenethylamine. Whole mononuclear cell sonicate is incubated with saturating concentrations of dopamine, S-adenosyl-L-methionine and magnesium chloride in sodium-potassium phosphate buffer at pH 7.3. An organic solvent extraction using ethyl acetate is then used for product separation, followed by high-performance liquid chromatography with electrochemical detection for product separation and quantification. This method allows both O-methylated products, 3-methoxytyramine and 4-methoxy-3-hydroxyphenethylamine, to be isolated and quantified separately. The apparent Michaelis constants for dopamine and S-adenosyl-L-methionine using this method are similar to values reported previously (0.51 and 14 microM, respectively). The optimal concentration of magnesium chloride is eight to ten times higher than previously reported. No endogenous inhibitors were apparent using this assay. The within-day coefficient of variation using this method is 7% when measuring 3-methoxytyramine and 5% when measuring 4-methoxy-3-hydroxyphenethylamine. The between-day coefficient of variation is 11%. Mononuclear cell COMT activity can be detected using protein concentrations as low as 0.75 mg/ml, corresponding to 2-3 ml of whole blood. The small amount of blood required per sample allows multiple sample analysis from a single patient, including infants.

Adult↗
PubMed1991

Bubbles of learning.

Explore the source record for details and available documents.

Administrative Personnel↗
PubMed1990

Coping with change in the NHS: a frontline district's response to AIDS.

The core of this paper is a case study of how a District Health Authority (Paddington and North Kensington, now Parkside DHA following a recent merger with Brent DHA) in Inner London responded to a major new health care issue of the 1980s--Aids, but the paper also seeks to locate this case study material within wider debates. What theories are there of organisational change which could be used to illuminate policy and service change in the health care sector? How, indeed, do we best study change in health care organisations? The paper is thus in three parts. In the first section we identify some streams of literature which act as a frame of reference defining our initial research question and discuss implications for methodology. The second section presents the case itself, while the last section discusses some emerging findings.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Managing strategic service change in the NHS.

This paper reports some early findings from a major research project which explores strategic service change in the NHS in the post-Griffiths era. We begin by briefly reviewing the relevant literature on change and general management in the NHS, and go on to outline the particular features of the research design. We then isolate some key emergent themes from a preliminary analysis of the data, highlighting two themes in greater depth. In our final section, we will attempt to reflect on some of the common factors associated with the achievement of strategic change. The project is funded by the NHSTA and a consortium of eight Regional Health Authorities.

Administrative Personnel↗
PubMed1986

The effects of captopril on serum digoxin and urinary urea and digoxin clearances in patients with congestive heart failure.

The effect of captopril as long-term treatment in 20 patients with congestive heart failure has been studied in a double-blind trial. Captopril caused a significant increase in serum digoxin levels. No patients developed evidence of digoxin toxicity. Serum and total body potassium rose and the frequency of ventricular arrhythmias showed a modest decline. Creatinine clearance and radioisotopically measured glomerular filtration rate fell, but there was a poor relationship between these and the increase in serum digoxin. In a further open study on 12 patients, creatinine, urea, and digoxin clearance were significantly reduced by captopril. However, digoxin clearance declined more than creatinine clearance (89 +/- 25 mumol/L to 69 +/- 22 mumol/L and 81 +/- 14 mumol/L to 72 +/- 19 mumol/L, respectively, p less than 0.05 for the difference). Fractional excretion of urea and digoxin filtered at the glomerulus declined, indicating greater tubular reabsorption or reduced tubular secretion of these compounds. Captopril causes an increase in serum digoxin by reducing renal clearance of the drug.

Captopril↗
PubMed1986

Liver dysfunction in haemophilia.

Liver function was studied in 139 of 291 haemophiliacs known to a single Regional Haemophilia Centre including patients with classical haemophilia, Christmas disease and von Willebrand's disease. In 57 patients, six-monthly liver function tests over a five year period were also available. Thirty-nine of the 139 patients had had jaundice or hepatitis and 56 had a positive test for HBsAb in the blood although few of these had had an identifiable clinical illness. Fifty-eight haemophiliacs had elevated serum aminotransferases at the time of study, but the five year review revealed only six patients who had had persistently abnormal results, although none had clinically evident liver disease. Liver dysfunction was unrelated to a history of hepatitis, to a positive HBsAb test, or to age, type of haemophilia, factor level or frequency of factor replacement treatment. Abnormalities of liver function in haemophilia appear to be unrelated to past or present hepatitis B infection in most cases and may not be related to any single transmitted infectious agent.

Adult↗
PubMed1983

The haemophilic patient's self-perception of changes in health and life-style arising from self-treatment.

Twenty three adults and twenty children with haemophilia, all on self-treatment, participated in the present study. They were interviewed as to how they perceive the effects of self-treatment upon various aspects of their life. It was found that the ability to treat themselves was perceived by patients as a great improvement over their previous treatment regimes for which they had had to go to hospital. Twelve of the adult patients had participated in our previous studies concerned with the social an psychological aspects of haemophilia. The analysis of the responses of these twelve patients showed that self-treatment is perceived so positively that some of the patients' earlier perceptions were distorted to correspond with their present and more optimistic perceptions of their condition. However, the number and type of psychosomatic symptoms was found to be unchanged by self-treatment and the unemployment rate has not decreased.

Adolescent↗
PubMed1978

Neurophysiological basis of directional hearing in amphibia.

Discrete regions of neural tissue along the anterior-posterior axis of the torus semicircularis act as resonators, each one broadly tuned to a different range of frequencies, and each one responding optimally to the incident sound from a different direction. In this way, a map of auditory space is represented in the midbrain.

Animals↗
PubMed1978

Dynamics of the amphibian middle ear.

Using laser speckle interferometry, we show that the directional information of acoustic signals is encoded in the motion of eardrum. Moreover, the frequency sensitivity of the auditory system is determined by the mechanical properties of the middle ear, which acts like a damped resonator.

Animals↗