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Biomedical subjects

M Hanlon

Publications and source records attributed to M Hanlon.

At least 19 recordsLinked to original sources
PubMed2003

Diagnostic testing and discharge coding for whooping cough in a children's hospital.

OBJECTIVE: To evaluate the diagnostic pathways for whooping cough in a large urban paediatric hospital to inform assessment of the relative merits of notification and hospitalization data for measuring pertussis disease burden in Australian children. METHODS: All laboratory requests for Bordetella pertussis (BP) culture or serology between 30 June 1997 and 30 June 1999 were reviewed and cross-checked against discharge diagnoses with International Classification of Disease (ICD) codes A37.0, 033.0 (whooping cough due to BP) or 37.9, 033.9 (whooping cough due to unspecified organisms). Culture-positive (CP) cases were defined as a positive culture or polymerase chain reaction for BP. Culture-negative (CN) cases either fulfilled the current Australian clinical case definition (>/=14 days of cough with one or more of paroxysms, whoop, post-tussive vomiting), or had a cough illness with either positive BP serology or documented contact with an individual coughing for >14 days. In infants <6-months-old, a coughing illness with apnoea and negative investigations for other causes was also accepted. Culture positive and CN cases were cross-referenced with notification data. RESULTS: During the study period, laboratory tests for BP were performed in 677 children, of whom 230 were hospitalized and 71 (31%) had an eligible ICD code at discharge; 29 were CP, 40 CN, and two (3%) were misclassified. A further 14 CP children were not admitted. Although 61 hospitalized cases (88%) fulfilled notification criteria, including 32 (80%) of CN cases, only 26 (90%) of CP and eight (20%) of CN cases were notified. CONCLUSIONS: Notifications substantially under-enumerate hospitalized infant cases, especially those without positive laboratory tests. Hospital discharge data add significantly to surveillance for pertussis, particularly in infancy where most severe cases occur.

Age Distribution↗
PubMed2002

Serological diagnosis of pertussis: evaluation of IgA against whole cell and specific Bordetella pertussis antigens as markers of recent infection.

In Australia, notification of pertussis cases in older children or adults has increased significantly in recent years. In most cases, laboratory diagnosis is based only on a positive serological test for IgA antibody against whole cell Bordetella pertussis. During a 3-month period, 318 consecutive sera submitted for diagnosis of pertussis were tested for IgA antibody against whole cell (WC) sonicated B. pertussis, pertussis toxin (PT), filamentous haemagglutinin (FHA) and pertactin (PRN). Results of one or more of these tests were positive in sera from 175 subjects and clinical information was obtained by telephone interview from 90 subjects. Using a clinical case definition as the reference standard, the sensitivities of the four IgA assays were variable but quite low (24-64%), but the specificities were high (93-98%). For diagnosis of pertussis in subjects with a compatible clinical illness, these and other findings support the use of serological testing for IgA antibody.

Adolescent↗
PubMed2001

ERK2- and p90(Rsk2)-dependent pathways regulate the CCAAT/enhancer-binding protein-beta interaction with serum response factor.

The serum response element (SRE) of the c-fos promoter is a convergence point for mitogenic signaling pathways. Several transcription factors regulate SRE, including serum response factor (SRF), ternary complex factors, and CCAAT/enhancer-binding protein-beta (C/EBPbeta). C/EBPbeta can interact with both SRF and the ternary complex factor family member Elk-1, but only in response to activated Ras. Transactivation of the SRE by C/EBPbeta is also greatly stimulated by Ras. The Ras effectors that signal to C/EBPbeta are unknown. In this report, we demonstrate that a consensus MAPK site in C/EBPbeta is necessary for Ras stimulation of both C/EBPbeta-SRF interaction and transactivation of the SRE by C/EBPbeta. To dissect signaling pathways activated downstream of Ras, different Ras effector constructs were analyzed. We show that activated forms of Raf and phosphatidylinositol 3-kinase stimulate C/EBPbeta-SRF interaction. We also show a novel selectivity for the MAPK family member ERK2, where dominant-negative ERK2, but not dominant-negative ERK1, blocks Ras stimulation of C/EBPbeta-SRF interaction. In addition, recombinant C/EBPbeta protein is phosphorylated by ERK2, but not by ERK1, in vitro. Finally, we demonstrate a requirement for p90(Rsk2) in regulation of C/EBPbeta-SRF interaction. These data show that multiple Ras effectors are required to regulate C/EBPbeta and SRF association.

3T3 Cells↗
PubMed2001

Storage at -3 degrees C for 24 h alters the immunogenicity of pertussis vaccines.

The immunogenicity of pertussis antigens in an acellular and a whole-cell triple antigen vaccine used for childhood immunisation was assessed in murine models after storage of vaccines below 0 degree C. Swiss outbred and Balb/c mice received DTPa or DTPw vaccine or placebo. Vaccines were stored at 2-8 degrees C (ideal), or at -3 degrees C for 24 h. Pre and post immunisation IgG responses to pertussis toxin (PT), filamentous haemagglutinin (FHA) and pertactin (PRN) were measured using enzyme immunoassays (EIA). In Balb/c mice, responses to pertactin after receiving adversely stored DTPa were significantly reduced (P = 0.005, difference in GMCs 145.9% [24.6-385.4%]). A reduction in GMC to pertactin was also seen in response to adversely stored DTPw (P = 0.190,224.1% [83.8-599.2%]). Outbred mice receiving adversely stored DTPa had lower IgG antibody responses to FHA than those receiving correctly stored vaccine (P = 0.002,522.2% [26.1-2155.6%]). Outbred mice also had a significantly lower response to FHA after administration of DTPw (P = 0.009,14.0% [3.8-51.9%]). Responses to DTPa in both strains generally were greater than those to DTPw. Storage of pertussis vaccines below 0 degree C appears to alter the immunogenicity of PRN and FHA. Further study is required to determine the effects of such storage on vaccine protective efficacy.

Adhesins, Bacterial↗
PubMed2001

Characterization of C/EBPbeta isoforms in normal versus neoplastic mammary epithelial cells.

A member of the CCAAT Enhancer Binding Proteins (C/EBPs) family of transcription factors, C/EBPbeta, has recently proven to be an important player in both growth and differentiation of the epithelial cells in the mammary gland. When the gene for C/EBPbeta is disrupted in mice, these mice fail to either develop normal mammary ducts during puberty or pregnancy, or to lactate upon parturition. C/EBPbeta can be present in cells in three isoforms: C/EBPbeta-1, -2, and -3. These isoforms have the same carboxy terminus but different N-termini due to alternative translational initiation at three different initiator codons within the C/EBPbeta mRNA. Using a commercially available antibody specific to the C-terminus of C/EBPbeta and a novel antibody specific to the N-terminus of C/EBPbeta-1, we have uncovered a striking difference in the forms of C/EBPbeta present in normal mammary epithelial cells versus breast cancer cell lines. C/EBPbeta- 1 is found exclusively in normal mammary epithelial cells, whereas C/EBPbeta- 2 is found only in dividing cells, both normal and neoplastic. Our preliminary data suggest that the prevalent form of C/EBPbeta in cancer cells, C/EBPbeta- 2, can activate genes which push the cell to divide, such as cyclin D1.

Antibodies↗
PubMed2000

C/EBP beta and Elk-1 synergistically transactivate the c-fos serum response element.

BACKGROUND: The serum response element (SRE) in the c-fos promoter is a convergence point for several signaling pathways that regulate induction of the c-fos gene. Many transcription factors regulate the SRE, including serum response factor (SRF), ternary complex factor (TCF), and CCAAT/enhancer binding protein-beta (C/EBPbeta). Independently, the TCFs and C/EBPbeta have been shown to interact with SRF and to respond to Ras-dependent signaling pathways that result in transactivation of the SRE. Due to these common observations, we addressed the possibility that C/EBPbeta and Elk-1 could both be necessary for Ras-stimulated transactivation of the SRE. RESULTS: In this report, we demonstrate that Elk-1 and C/EBPbeta functionally synergize in transactivation of both a Gal4 reporter plasmid in concert with Gal4-SRF and in transactivation of the SRE. Interestingly, this synergy is only observed upon activation of Ras-dependent signaling pathways. Furthermore, we show that Elk-1 and C/EBPbeta could interact both in an in vitro GST-pulldown assay and in an in vivo co-immunoprecipitation assay. The in vivo interaction between the two proteins is dependent on the presence of activated Ras. We have also shown that the C-terminal domain of C/EBPbeta and the N-terminal domain of Elk-1 are necessary for the proteins to interact. CONCLUSIONS: These data show that C/EBPbeta and Elk-1 synergize in SRF dependent transcription of both a Gal-4 reporter and the SRE. This suggests that SRF, TCF, and C/EBPbeta are all necessary for maximal induction of the c-fos SRE in response to mitogenic signaling by Ras.

3T3 Cells↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1999

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↗
PubMed1997

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↗