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M Hanlon

Publications and source records attributed to M Hanlon.

27 records · Page 2Linked to original sources
PubMed1996

Repeated prevalence surveys of paediatric hospital-acquired infection.

Hospital-acquired infection (HAI) results in an enormous burden of excess morbidity, mortality and cost in both adults and children. Monitoring HAI is difficult, especially with limited resources, but it is vital if infection control measures are to be appropriately implemented and assessed. Cross-sectional prevalence surveys, repeated every six months, have been used effectively to monitor HAI in adults, but this technique has not been previously employed in the paediatric population. We performed prevalence surveys of HAI on a single day once every six months for five years, using a standardized questionnaire. Of the 1623 inpatients surveyed, 125 (7.7%) had HAI and 352 (21%) had community-acquired infection. In those with HAI, central-line infections, pneumonia, and wound infections predominated. A hospital stay of greater than seven days was associated with a sixfold increase in the risk of HAI. In addition, admission to a paediatric or neonatal intensive care unit, the presence of a urinary or vascular catheter, the presence of an endotracheal tube, immunosuppression and recent surgery were all associated with a significantly increased risk of HAI. In contrast to other studies, younger children were not at increased risk of HAI; admission to the neonatal unit, rather than age per se, was associated with increased risk. We conclude that repeated prevalence surveys enable simple and cost-effective assessment of HAI, facilitating appropriate infection control interventions. They should be used more widely in the paediatric setting.

Age Factors↗
PubMed1996

Differing antibody responses to Haemophilus influenzae type b after meningitis or epiglottitis.

Two common forms of invasive disease due to Haemophilus influenzae type b (Hib) are epiglottitis and meningitis. It is not known why some children develop epiglottitis and others meningitis. To examine the hypothesis that epiglottitis occurs in children who may have been previously exposed to Hib, and who would therefore exhibit a more vigorous antibody response in convalescence, we measured levels of antibody to Hib capsule in 92 children. Geometric mean convalescent-phase IgG, IgA, IgM and total antibody levels were significantly higher in 45 children with epiglottitis than in 47 with meningitis, even after adjustment for age differences (mean total antibody, 95% confidence intervals: meningitis 0.38, 0.34-0.43; epiglottitis: 2.25, 2.0-2.54 micrograms/ml). However, contrary to previous reports, a poor antibody response was only observed in a minority of children with meningitis; the antibody response of the majority was indistinguishable from that observed in children with epiglottitis.

Acute-Phase Reaction↗
PubMed1994

Mode of binding of folate analogs to thymidylate synthase. Evidence for two asymmetric but interactive substrate binding sites.

Human thymidylate synthase is a polymeric protein composed of two subunits with identical primary structures. In this study we determined the binding affinities of 5,10-methylene tetrahydropteroyltetraglutamate (folate substrate) and a group of close structural folate analog inhibitors. Thymidylate synthase bound both mono and polyglutamylated folate substrates and analogs more tightly in the presence of deoxyuridylate. These results and product inhibition studies confirmed that the orders of substrate addition and product release from thymidylate synthase were similar for mono and polyglutamylated substrates. Equilibrium dialysis studies showed that the folate substrate in a ternary complex with deoxyuridylate bound to one of the subunits (site A) with a Kd of 720 nM. The binding of the substrate to the second subunit (site B) was much weaker, and the Kd could not be determined by this method. However, dissociation constants for each subunit could be measured for the folate analog inhibitors, and, depending on the inhibitor, the relative Kd value for each subunit varied substantially. For example, formyl-5,8-dideazafolate and tetraglutamylated 10-propargyl-5,8-dideazafolate bound to both sites with similar Kd values, whereas D1694Glu4 bound to subunit A with a higher affinity (Kd = 1.0 nM) than to subunit B (Kd = 30 nM). In contrast, 1843U89 (mono or diglutamylated form) had a much higher affinity for subunit B (Kd approximately 0.1 nM) compared with subunit A (Kd approximately 400 nM). Enzyme inhibition kinetic analyses showed that the Ki values of 1843U89 were quite low (0.1 nM) and that the inhibition was noncompetitive. In contrast, the other folate analogs inhibited the enzyme via mixed inhibition (i.e. both the Km for the folate substrate and the Vmax were altered). We conclude that the two subunits of thymidylate synthase bind folate substrates and analogs differently and that the asymmetric binding of the ligands is the major factor that determines the inhibition kinetics of each folate analog inhibitor.

Binding Sites↗
PubMedDate not supplied

Central compartment pressure monitoring following clubfoot release.

Thirty-nine clubfeet undergoing primary soft tissue release for idiopathic clubfoot deformity had intrinsic compartment pressure monitoring for 36 h after surgery. This was done to determine whether pressures might be elevated to levels, and for durations, such that an intrinsic compartment syndrome might develop. Two groups were identified: in group 1 (23 feet) pressures were never elevated to > 20 mm Hg; in group 2 (16 feet) pressures > 30 mm Hg for a duration of at least 12 h were found. In a subgroup of group 2 (4 of 16 feet), pressures were > 50 mm Hg for at least 12 h. There was no statistical correlation between pressure recordings and surgeon, tourniquet time, severity of deformity, extent of release, and type of cast used. Thus 40% of feet are at risk of developing pressures that could cause an intrinsic compartment syndrome.

Clubfoot↗