PubMed Health⌕ Search

Biomedical subjects

P Littleton

Publications and source records attributed to P Littleton.

17 recordsLinked to original sources
PubMed1993

Cardiac transplantation affects ventricular expression of brain natriuretic peptide.

OBJECTIVE: The aim was to examine the ventricular expression of brain natriuretic peptide (BNP) in the transplanted human heart. METHODS: Serial right ventricular biopsies (n = 68) and plasma samples (n = 68) were obtained for measurement of BNP and atrial natriuretic peptide (ANP) from 14 orthotopic cardiac transplant recipients from 1-74 weeks after transplantation. Right ventricular specimens (n = 10) were also obtained from normal hearts during necropsy as controls. RESULTS: Mean ventricular BNP in cardiac transplant recipients was higher (p < 0.05) than in normal hearts, at 13531(SEM 2244) pg.mg-1 soluble protein (range 3232-109448) v 56(11) pg.mg-1 (range 16-91). Ventricular BNP and ANP values were correlated (r = 0.57, p < 0.05). Plasma BNP concentrations were higher (p < 0.05) than plasma ANP concentrations, at 202(16) pg.ml-1 (range 84-655) v 100(12) pg.ml-1 (range 8-484), and were raised (p < 0.05) in comparison with normal plasma BNP concentrations of 20(1.8) pg.ml-1 (range 10-23). Mean ventricular BNP was correlated with time after transplant (r = 0.72, p < 0.05, n = 68) and with mean plasma BNP (r = 0.80, p < 0.05, n = 14). There was no significant relationship between BNP levels and intracardiac or systemic blood pressure, or prednisolone dose (0.1-0.3 mg.kg-1.d-1). The increase in ventricular BNP with time after transplant was not explained by cardiac rejection assessed from histology, and plasma BNP was not significantly increased during rejection episodes. CONCLUSIONS: High levels of BNP are synthesised and secreted by the transplanted human ventricle, and the transplanted ventricle may be an important source of circulating BNP. The significant positive association between ventricular BNP and time after transplant suggests a possible self compensatory mechanism or functional adaptation of the transplanted heart which may be beneficial to ventricular function.

Adolescent↗
PubMed1992

Atrial natriuretic peptide, cyclic guanosine monophosphate and sodium excretion during postnatal adaptation in male infants below 34 weeks gestation with severe respiratory distress syndrome.

The role of atrial natriuretic peptide (ANP), in the perinatal period, is at present unclear. In adults urinary cyclic guanosine monophosphate (cGMP) is considered an index of the biological activity of plasma ANP. The aim of this study was to determine the relationship between plasma ANP, cGMP excretion (cGMPex) and sodium excretion (Naex) in preterm infants in the first days after birth. Sequential, 4 hourly, measurements of plasma ANP, cGMPex and Naex were made in 12 male neonates of median gestational age 27 weeks (range 25-33) and median birth weight 0.981 kg (range 0.635-2.029) over a median period of 5.2 days (range 2.3-10). The ratios of cGMPex to ANP and of Naex to cGMPex were each plotted against postnatal age. The ratio of cGMPex to ANP increased ten fold in the first 3-4 days after birth but then remained relatively constant; the ratio of Naex to cGMPex showed a steady increase from birth. We conclude that, in extremely immature infants, renal sodium loss in response to cGMP increases rapidly during the first 10 days after birth. In addition, after 3-4 days from birth, plasma ANP ia associated with a constant proportionate rate of cGMP excretion though, as the plateau ratio of cGMPex to ANP varied widely between babies, cGMPex cannot be used to predict plasma ANP in cross sectional studies. These changes may reflect postnatal adaptation and/or maturation of both ANP receptors and cGMP mediated cascades. In the immediate postnatal period, plasma ANP may also have a non-renal role.

Age Factors↗
PubMed1992

Atrial natriuretic peptide in the diagnosis of patent ductus arteriosus.

The aim of this study was to measure plasma atrial natriuretic peptide in preterm infants with a patent ductus arteriosus before and after closure with indomethacin. Atrial natriuretic peptide was measured in 28 preterm infants with clinical and echocardiographic evidence of a patent ductus arteriosus and in eight preterm infants who did not develop clinical evidence of a patent ductus arteriosus. Plasma concentration of atrial natriuretic peptide was measured by radioimmunoassay. In 18 infants the patent ductus arteriosus closed after one course of indomethacin; atrial natriuretic peptide levels decreased from median 1240 pg/ml (range 201-5483 pg/ml) to 266 pg/ml (range 62-1108 pg/ml). In four infants the patent ductus arteriosus closed after two courses of indomethacin and two infants had surgical ligation after indomethacin treatment failed. The patent ductus arteriosus closed spontaneously in four infants (atrial natriuretic peptide median level 152 pg/ml, range 61-495 pg/ml). In the eight infants without patent ductus arteriosus, atrial natriuretic peptide level was median 224 pg/ml (range 38-876 pg/ml). Measurement of plasma atrial natriuretic peptide concentration has a role in predicting when indomethacin treatment is indicated.

Atrial Natriuretic Factor↗
PubMed1989

The bioavailability and pharmacokinetics of morphine after intravenous, oral and buccal administration in healthy volunteers.

1. The absolute bioavailability of morphine from oral aqueous solution, a controlled release oral tablet (MST-Continus) and a controlled release buccal tablet has been investigated in six healthy volunteers. 2. Analysis of plasma samples for morphine and its active metabolite morphine-6-glucuronide (M6G) was by means of a differential radioimmunoassay technique. Absolute bioavailability for morphine was estimated to be 23.9% after oral solution, 22.4% after MST-Continus and 18.7% after the buccal tablet. Maximum plasma morphine concentrations were seen at 45 min (oral solution), 2.5 h (MST) and 6 h (buccal). 3. There was no difference in the amount of M6G appearing in plasma after intravenous, oral or buccal administration but the mean ratio of AUCs for M6G: morphine in plasma after intravenous morphine was 2 : 1 compared with 11 : 1 after oral and buccal morphine.

Administration, Buccal↗
PubMed1987

Subcutaneous infusion of bleomycin--a practical alternative to intravenous infusion.

The phase specificity and short half-life of bleomycin make it likely that it would be more effective when administered by continuous infusion. This is supported by studies using cell lines, as well as by animal studies and clinical experience in humans. This study was conducted to compare the pharmacokinetics of intravenous (IV) and subcutaneous infusions of bleomycin. The serum concentrations of bleomycin were measured using a sensitive and specific radioimmunoassay. The results demonstrate similar plasma concentrations and area under the curve for both routes. The subcutaneous infusions were well tolerated, without local discomfort or excoriation. Subcutaneous infusion of bleomycin may thus offer a practical alternative to IV infusions and can be administered to patients who are ambulatory and out of hospital.

Bleomycin↗
PubMed1985

Small intestinal transit time affects methotrexate absorption in children with acute lymphoblastic leukemia.

Serum methotrexate concentrations have been measured in 28 children with acute lymphoblastic leukaemia (ALL) following PO administration under standard conditions. Small-intestinal transit time, measured by the time taken for lactulose to pass from mouth to caecum, has been related with methotrexate absorption parameters. Small intestinal transit times ranged from 30 to 240 min. Children with longer transit times had later times of peak methotrexate concentration and tended to have a more erratic methotrexate absorption profile with two peaks. There appears to be an optimal transit time between 90 and 105 min for methotrexate absorption, with both faster and slower small-intestinal transit times producing lower peak concentrations as a fraction of the dose.

Adolescent↗
PubMed1982

A sensitive radioimmunoassay for budesonide in plasma.

Budesonide is a highly potent non-halogenated glucocorticoid with local anti-inflammatory properties. A sensitive radioimmunoassay for the measurement of the drug in unextracted plasma has been developed. Budesonide 21-hemisuccinate and budesonide 3-(O-carboxymethyl)oxime were conjugated to ovalbumin using the mixed anhydride method and antibodies to the haptens produced in sheep. The specificity of the antisera towards cortisol, and possible budesonide metabolites reflected the different sites of the attachment of the haptens to the carrier protein. An antiserum raised against the 3-(O-carboxy methyl)oxime conjugate was more specific (0.001% cross reaction) with respect to cortisol than the antiserum raised against the 21-hemisuccinate conjugate (0.344% cross reaction). Endogenous steroids at concentrations normally encountered in clinical samples, would not interfere with the measurement of budesonide. The radioimmunoassay was developed using the budesonide 3-(O-carboxy methyl)oxime antiserum, [3H]-budesonide and dextran coated charcoal phase separation. The theoretical limit of detection of the assay was 50 pg/ml. Budesonide was quantitatively recovered from normal human drug/free plasma at concentrations above 1 ng/ml (2.32 nmol/l) with a between batch variation of 12-15%. Budesonide was measured in the unextracted plasma of volunteers who had inhaled the drug from a pressurised aerosol spray.

Animals↗