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Biomedical subjects

M Hanlon

Publications and source records attributed to M Hanlon.

At least 19 recordsLinked to original sources

Differing serologic responses to an haemophilus influenzae type b polysaccharide-neisseria meningitidis outer membrane protein conjugate (PRP-OMPC) vaccine in australian aboriginal and caucasian infants - implications for disease epidemiology.

This study compared Hib antibody responses to a single lot of PRP-OMPC vaccine given at 2, 4 and 12 months to 57 Aboriginal infants in rural areas of the Northern Territory and 56 Caucasian infants in Sydney, Australia. The Aboriginal infants had lower levels of antibody in cord blood (P>0.05), which were significantly lower (P<0.02) by 2 months of age. Antibody responses to one or two doses of vaccine, measured at 4 and 12 months of age, were similar but the geometric mean titre following the booster dose in Aboriginal infants was significantly lower (1.98 vs. 6.04 mcg/ml, P = 0.002). Low preimmunisation antibody is consistent with the early onset of Hib disease in Aboriginal infants before immunisation. Lower responses to boosting could correlate with persistence of Hib colonisation in indigenous populations.

Age Factors↗

Acellular vaccines for preventing whooping cough in children.

OBJECTIVES: Routine use of whole cell pertussis vaccines was suspended in some countries in the late 1970s and early 1980s, leading to a resurgence of whooping cough. Acellular pertussis vaccines containing purified or recombinant Bordetella pertussis antigens were developed in the hope that they would be as effective but less toxic than the whole cell vaccines. The objective of this review was to assess the effects of acellular pertussis vaccines in children. SEARCH STRATEGY: The Cochrane Controlled Trials Register and Medline were searched up to January 1998. SELECTION CRITERIA: Double-blind randomised efficacy and safety trials of acellular pertussis vaccines in children, with active follow-up of participants and laboratory verification of pertussis cases. DATA COLLECTION AND ANALYSIS: One reviewer assessed trial quality and extracted data. MAIN RESULTS: Six efficacy trials and 45 safety trials were included. Acellular pertussis vaccines with three or more pertussis vaccines were more effective than those with one or two antigens. They were also more effective than one type of whole cell pertussis vaccine, but less effective than two other types of whole cell vaccines. Differences in trial design precluded pooling of the efficacy data and results should be interpreted with caution. Most systemic and local adverse events were significantly less common with acellular than with whole cell pertussis vaccines. REVIEWER'S CONCLUSIONS: Multi-component acellular pertussis vaccines are effective, and show less adverse effects than whole cell pertussis vaccines. However in areas where whooping cough is more likely to be fatal, the higher toxicity of some whole cell vaccines may be offset by their increased effectiveness.

Age Factors↗

Phoenix date palm injuries: a review of injuries from the Phoenix date palm treated at the Starship Children's Hospital.

BACKGROUND: The purpose of this study was to review patients treated for penetrating Phoenix date palm injuries. Documentation of the clinical behaviour of these injuries was sought as they have different clinical outcomes to other foreign body injuries. METHODS: Data was collected via a retrospective review of patient files and imaging studies of all patients with foreign body injury admitted to the Orthopaedic Service of Starship Children's Hospital between 1992 and 1997. RESULTS: Of 250 patients admitted with foreign body injuries, 21 cases were identified as caused by the Phoenix date palm. The age range was 5 to 12 years. There was a median delay of 43 days between the time of injury and presentation to hospital. An average of 1.3 operations were performed on each patient. Ultrasound was used in 12 cases, foreign body was identified in 10 patients--a sensitivity of 83%. Intraoperative ultrasound was also found to be beneficial in three of these cases. CONCLUSIONS: Phoenix date palm injuries often have a protracted course. The initial diagnosis and treatment of such injuries is often delayed. Fracturing and fragmentation of the barbs may occur and multiple surgical procedures may be required to remove all of the foreign material. The Phoenix date palm barbs may cause a severe tissue reaction with sterile granulomatous synovitis and bony pseudotumour formation. A high level of suspicion on history taking and surgical exploration is needed. Total synovectomy for delayed joint or tendon sheath involvement may be required when fragmentation has occurred. Ultrasound has higher sensitivity for detection of thorn foreign bodies than magnetic resonance imaging.

Child↗

Pertussis antibody levels in infants immunized with an acellular pertussis component vaccine, measured using whole-cell pertussis ELISA.

A commercially available whole-cell pertussis IgG ELISA was used to test the response of 137 2-month-old infants to immunization with a trivalent acellular pertussis vaccine. The pre-immunization geometric mean (GM) IgG index was 6.96 (95% confidence interval (CI) 5.88-8.04) and the postimmunization GM index was 13.16 (95% CI 12. 20-14.11), P < 0.001. Eighty percent of subjects (110/137) had a significant 1.5-fold increase of pertussis IgG index (97/137, 71%) or a postimmunization IgG index > 10 (93/137, 68%). In single antigen ELISA, 83% showed at least a fourfold increase in pertussis toxin-specific IgG (PT-IgG) and 91% showed an increase in IgG specific for filamentous haemagglutinin (FHA-IgG). Four percent had high pre- immunization antibody levels (index > 20), likely to reflect recent maternal exposure to pertussis. This correlated with a smaller increase in pertussis IgG index. A decline in pertussis IgG index postimmunization occurred in 17/24 infants (71%) whose pre-immunization IgG index was > 10. This postimmunization pertussis IgG index was not significantly different to that of infants with a low pre-immunization index. A similar trend was noted with PT-IgG and FHA-IgG results. The whole-cell ELISA can detect a response to acellular pertussis vaccination in most infants if both antibody index and degree of seroconversion are calculated and at least one criterion is satisfied.

Antibodies, Bacterial↗

Reducing nosocomial pressure ulcers in an acute care facility.

In 1996, a nursing committee at an acute care facility organized the first pressure ulcer point prevalence survey for that hospital. In 1996, hospital-acquired pressure ulcers were 90 percent of the predicted prevalence rate; in 1997, the rate dropped to 59 percent of the predicted prevalence and in 1998, to 53 percent of the predicted prevalence. The severity index decreased markedly from 291 (1996) to 98 (1997) then to 62 (1998). These improvements are attributed to the purposeful addition of multidimensional interventions, including best practices and research-based protocols, to prevent and treat nosocomial pressure ulcers.

Benchmarking↗

Ras regulates the association of serum response factor and CCAAT/enhancer-binding protein beta.

The serum response element (SRE) is a promoter element essential for transcriptional activation of immediate early genes, such as c-fos and early growth response-1, by mitogenic signals. Several transcription factors bind the SRE, including the serum response factor (SRF), the ternary complex factor, and the CCAAT/enhancer-binding protein beta (C/EBPbeta). The C/EBPbeta mRNA encodes three translation products of 38, 35, and 20 kDa. p35-C/EBPbeta activates transcription of the SRE in an SRF-dependent fashion, whereas p20-C/EBPbeta, which initiates at an internal in-frame methionine, lacks a transactivation domain and inhibits transcription. We show that SRF and C/EBPbeta interact in vivo through the DNA binding domain of SRF and the C terminus of C/EBPbeta common to p35/38 and p20. Therefore, like the ternary complex factor, C/EBPbeta may be recruited to the SRE not only by binding to the DNA, which is not a high affinity site, but also by protein-protein interactions with SRF. Strikingly, in both the mammalian two-hybrid assay and in vivo coimmunoprecipitations, the association of SRF and p35-C/EBPbeta but not p20-C/EBPbeta is dramatically stimulated by activated Ras. Furthermore, mutation of the threonine within a mitogen-activated protein kinase consensus motif in the C terminus of C/EBPbeta eliminates the response to Ras. These results suggest a new mechanism by which mitogenic signals may influence transcription activity of the SRE by selectively promoting protein-protein interactions between SRF and the transactivator p35-C/EBPbeta.

3T3 Cells↗

Effects of information on parental knowledge of febrile convulsions.

The purpose of this study was to study the effects of giving information to parents with febrile convulsive children. All parents of children with febrile convulsions who are seen at Worcester Royal Infirmary are given information. Fifty parents of children who had had a first febrile convulsion during May 1996 to December 1996 were interviewed by telephone from July to September 1997. The same questions were asked of 50 parents of children who came to a community health clinic and who had not had febrile convulsions. The design used open questions and covered medical history, general child health knowledge and knowledge of febrile convulsion. The answers were compared using a chi-squared test (significance level P < 0.05). Possible confounding factors were tested by a correlation test. No difference was found between the two groups in family structure, housing, and general child health knowledge. Information about febrile convulsions was retained by informed parents. Both groups thought the given information was useful and should be written in the child health record book. Information about febrile convulsions was remembered by parents.

Child, Preschool↗

Rotationplasty in skeletally immature patients. Long-term followup results.

Twenty-one skeletally immature patients with a Grade IIB osteosarcoma about the knee were treated with a modified Van Nes rotationplasty. Fourteen patients were followed up for 4 to 10.5 years (mean followup, 8 years). Functional assessment using Enneking's method showed all had good or excellent results. No patient thought that the reconstruction affected their ability to achieve recreational, sporting, or career goals. The reconstruction is durable and is not associated with an increase in late complications.

Adolescent↗

Nursing staff's perceptions and experiences of primary nursing practice in intensive care 4 years on.

This study explores the perceptions of staff who have been practising primary nursing for more than 4 years in intensive care. It considers what primary nursing is, what its benefits, disadvantages, and role impact are and other issues within an intensive care setting from the staff's perceptions and experiences. Although many of the perceived advantages and disadvantages are similar to experiences from other areas of nursing, there are some differences. The differences seem to relate to the way primary nursing is practised within the research setting-each primary nurse works with the same small team of associates, which is perceived as providing added benefits in terms of personal support and development of junior staff. The changes in role are seen to reflect other models in the literature which focus on becoming more patient centred and on working therapeutically. A number of future issues are addressed.

Attitude of Health Personnel↗

Tetanus immunity in an older Australian population.

OBJECTIVE: To evaluate the effectiveness in older Australians of the current tetanus vaccination program. DESIGN: A cross-sectional survey of tetanus immunity (enzyme immunoassay of serum samples) in an older population in New South Wales. Self-reported history of tetanus vaccination was compared with serologically measured immunity. PARTICIPANTS: 430 randomly selected adults, 49 years of age and older, from the Blue Mountains Eye Study population. RESULTS: Fifty-two per cent (95% confidence interval [CI], 47%-57%) of adults 49 years of age and older had protective levels of tetanus antitoxin ( > 0.15 IU/mL). There was a significant decline in the prevalence of immunity with increasing age (chi 2 for linear trend, P = 0.036), and women were less likely to be immune regardless of their age (Mantel-Haenszel weighted odds ratio, 0.65; CI, 0.43-0.92). Thirty-five per cent (95% CI, 31%-40%) of all participants reported that they had been vaccinated in the preceding 10 years. Although self-reported tetanus vaccination history was associated with tetanus immunity, it was neither sensitive nor specific as a test for immunity. CONCLUSIONS: About half the adults 49 years of age and older in the Blue Mountains area of New South Wales do not have protective levels of tetanus antitoxin because of inadequate vaccination coverage in this age group. Vaccination history is not a reliable indicator of tetanus immunity and a system is needed for accurate recording of adult vaccination.

Adult↗

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↗

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↗

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↗