Biomedical subjects

A J Henderson

Publications and source records attributed to A J Henderson.

At least 19 recordsLinked to original sources

PubMed2007

Maternal testosterone in pregnancy and atopic outcomes in childhood.

BACKGROUND: In mice, androgens downregulate Th2 cytokine responses, but whether androgen levels during pregnancy might influence the development of allergy in the offspring has not been studied. METHODS: In the Avon Longitudinal Study of Parents and Children (ALSPAC), a population-based birth cohort of 14 541 pregnancies, we related maternal blood total testosterone during pregnancy, measured in a subset of the cohort, to allergic outcomes in the offspring, including asthma, hayfever, eczema (n=543) and wheezing (n=532) at 69-81 months, and atopy (positive skin prick test to Dermatophagoides pteronyssinus, cat or grass, n=386) and blood total immunoglobulin E (IgE; n=314) at 7 years. We used logistic and linear regression to analyse binary outcomes and log-transformed IgE, respectively, controlling for potential confounders. RESULTS: Maternal testosterone was negatively associated with total IgE in boys [adjusted geometric mean ratio (GMR), per doubling of testosterone, 0.33 (0.20-0.55), P=0.000038 (n=168)], but not in girls [GMR 1.04 (0.53-2.06), P=0.91 (n=146)], P-value interaction 0.0086. The effect in boys was even stronger in the absence of maternal atopic disease. Testosterone was not associated with skin test positivity or atopic disease in either sex. CONCLUSIONS: Higher testosterone levels in pregnancy are associated with lower IgE production in boys.

Adolescent↗

PubMed2006

Highlights in asthma 2005.

It is usual at the end of a year for top tens to feature large in our collective consciousness. These inevitably include the occasional controversial selection and without fail will overlook a number of gems, whether in the field of literature, art, or science. The approaches to such compilations include personal selections, convening expert committees through to letting the market decide. However, it is well recognised that experts can be wrong and markets distorted. A novel approach to identifying the key publications in the field of medicine, Faculty of 1000 Medicine (http://www.f1000medicine.com), uses faculty evaluations to assign ratings to published papers within topics and categories, bringing a flavour of the dynamism of post hoc peer review to biological sciences that exists in other fields of scholarship. Archives of Disease in Childhood has also developed a market led system of peer evaluation through its web based top ten most read articles feature.

Acute Disease↗

PubMed2005

Maternal age of menarche is not associated with asthma or atopy in prepubertal children.

BACKGROUND: Maternal sex hormones in pregnancy can theoretically influence the developing fetal immune system and modulate the subsequent development of atopic disorders. Early onset of menarche has been linked to increased oestrogen levels in adult women. A study was undertaken to examine the association between early onset menarche in pregnant women and asthma and atopic status of their children at 7 years of age. METHODS: The Avon Longitudinal Study of Parents and Children (ALSPAC) is a longitudinal birth cohort study in which pregnant women, resident in Avon (UK), were recruited on the basis of an expected date of delivery between 1 April 1991 and 31 December 1992. Maternal age at menarche was assessed from prenatal questionnaires administered to the women. Clinical outcomes in the children were based on mothers' responses to self-completion questionnaires and included asthma, eczema, and hay fever. The atopic status of the child was objectively assessed by skin prick tests to a panel of common aeroallergens at the age of 7 years. Analyses used multivariable logistic regression with a diverse range of possible confounders. RESULTS: Complete data were available on 5765 woman and child pairs. The prevalence of ever reported asthma to 7 years was 20.4%, eczema 58.6%, hay fever 12.1%, and atopy (defined as any positive (>2 mm weal) response) was present in 20.6%. There were no significant differences in mean age of menarche between mothers of children with and without each of the primary outcomes. Adjusted odds ratios (95% CI) for the latest age of menarche (16+ years) compared with the lowest (<12 years) reference group were 1.41 (1.00 to 1.99) for asthma, 0.98 (0.73 to 1.91) for eczema, 0.95 (0.62 to 1.44) for hay fever, and 0.98 (0.68 to 1.42) for atopy. CONCLUSION: No consistent association was found between maternal age at menarche and asthma, eczema, hay fever or atopy in their children during early childhood.

Adolescent↗

PubMed2005

Prenatal paracetamol exposure and risk of asthma and elevated immunoglobulin E in childhood.

BACKGROUND: We recently found that paracetamol (acetaminophen) use in late pregnancy was associated with an increased risk of early wheezing in the offspring. OBJECTIVE: To see whether use of paracetamol in late pregnancy is associated with an increased risk of asthma, wheezing and other atopic outcomes in the child at school age. METHODS: In the population-based Avon Longitudinal Study of Parents and Children, we measured associations of paracetamol and aspirin use in late pregnancy (20-32 weeks) with asthma, hayfever, eczema (n = 8511) and wheezing (8381) in the offspring at 69-81 months, and with atopy (positive skin prick test to Dermatophagoides pteronyssinus, cat or grass, n = 6527) and blood total IgE (n = 5148) at 7 years. We used logistic and linear regression to analyse binary outcomes and log-transformed IgE, respectively, controlling for potential confounders. RESULTS: Use of paracetamol, but not aspirin, in late pregnancy was positively associated with asthma (odds ratios (ORs), comparing children whose mothers took paracetamol 'sometimes' and 'most days/daily' with those whose mothers never took it, 1.22 (95% confidence interval (CI): 1.06-1.41) and 1.62 (95% CI: 0.86-3.04), respectively; P trend = 0.0037), wheezing (ORs 1.20 (95% CI: 1.02-1.40) and 1.86 (95% CI: 0.98-3.55), respectively; P trend = 0.011), and total IgE (geometric mean ratios 1.14 (95% CI: 1.03-1.26) and 1.52 (95% CI: 0.98-2.38), respectively; P trend = 0.0034), but not hayfever, eczema or skin test positivity. The proportion of asthma attributable to paracetamol use in late pregnancy, assuming a causal relation, was 7%. CONCLUSION: Paracetamol exposure in late gestation may cause asthma, wheezing and elevated IgE in children of school age.

Acetaminophen↗

PubMed2004

Who should have a sleep study for sleep related breathing disorders?

By the time children are 5 years old more of their life will have been spent asleep than awake. Sleep medicine is therefore especially relevant in paediatrics. However, one recent survey showed that paediatricians' knowledge of sleep medicine is poor and that few paediatricians enquire about sleep as part of their general consultation.1

Child↗

PubMed2004

Umbilical cord trace elements and minerals and risk of early childhood wheezing and eczema.

It has been suggested that foetal nutrition might influence the inception of wheezing and atopic disorders in childhood but specific nutrients have not been implicated. In the Avon Longitudinal Study of Parents and Children umbilical cord samples were assayed for trace elements and minerals, and mothers were asked about wheezing and eczema in their children. Associations of cord concentrations of selenium, zinc, copper, manganese, magnesium, iron, lead and mercury with wheezing at 30-42 months, with wheezing patterns defined by the presence or absence of transient infant, later onset or persistent wheezing at 0-6 months and 30-42 months, respectively (n=2,044), and with eczema at 18-30 months (n=2,173), were analysed. Cord selenium was negatively associated with persistent wheeze (adjusted odds ratio (OR) per doubling concentration: 0.67). Cord iron was negatively associated with later onset wheeze (OR: 0.86) and with eczema (OR: 0.90). Children with high cord concentrations of selenium and iron were less likely than those with low concentrations to wheeze transiently in infancy. The level of foetal exposure to selenium and iron may possibly influence the risk of wheezing and eczema in early childhood although, in view of the multiple analyses carried out, it is possible that the main findings occurred by chance.

Biomarkers↗

PubMed2003

Management of parapneumonic effusion and empyema.

AIMS: To gather data on the clinical presentation of parapneumonic effusion and empyema and to examine the effect of different management strategies on short term outcomes. METHODS: Retrospective case note review of 48 children admitted to a tertiary unit between January 1998 and March 2001. Effusions were classified into three stages dependent on ultrasound findings. RESULTS: The stage of effusion was not associated with duration of previous symptoms or length of previous admission. An interventional procedure was performed on median day 2 of admission in 46 children: eight (17%) had an intercostal drain alone, 14 (29%) had an intercostal drain followed by intrapleural fibrinolytic therapy, and 24 (50%) had a thoracotomy. Three children who had an initial intercostal drain alone returned to theatre for thoracotomy, and two children who had intrapleural fibrinolysis returned for thoracotomy. Median length of stay (interquartile range) for each initial procedure was 15 days (6-20) for intercostal drain alone, 8 days (6-12) for fibrinolytic therapy, and 6.5 days (5-9) for thoracotomy. Stay for intercostal drain alone was significantly longer than for thoracotomy. CONCLUSION: Early surgical management of empyema is associated with a favourable outcome.

Adolescent↗

PubMed2002

Risk adjusted mortality of critical illness in a defined geographical region.

AIMS: To evaluate the performance of the Paediatric Risk of Mortality (PRISM) score in a population of UK children and to use this score to examine severity of illness adjusted mortality of critically ill children <16 years old in a defined geographical region. METHODS: Observational study of a defined population of critically ill children (<16 years old) admitted to hospitals in the South West Region between 1 December 1996 and 30 November 1998. RESULTS: Data were collected from 1148 eligible admissions. PRISM was found to perform acceptably in this population. There was no significant difference between the overall number of observed deaths and those predicted by PRISM. Admissions with mortality risk 30% or greater had significantly greater odds ratio for death in general intensive care units compared with the tertiary paediatric intensive care unit. CONCLUSIONS: Children with a high initial risk of mortality based on PRISM score were significantly more likely to survive in a tertiary paediatric intensive care unit than in general intensive care units in this region. However, there was no evidence from this study that admissions with lower mortality risk than 30% had significantly worse mortality in non-tertiary general units than in tertiary paediatric intensive care units.

Adolescent↗

PubMed2002

The PATRIARCH Study. Using outcome measures for league tables: can a North American prediction of admission score be used in a United Kingdom children's emergency department? PRISA And Triage In A Regional Children's Hospital.

OBJECTIVES: The use of league tables has become predominant in the healthcare culture of the United Kingdom. These tables are often based on measures that are viewed with scepticism by clinicians. This study was designed to test the validity of a North American risk of admission score, the PRISA, for use in a United Kingdom population of accident and emergency (A&E) attendees. METHODS: All attendees to a children's A&E department were scored using the PRISA for a single calendar month (November 2000) RESULTS: 701 children were studied in total. The results show that the PRISA applied to this population gives an area under the receiver operator curve of 0.76. Of the 701 patients studied, 206 (29.4%) were admitted. The PRISA predicted a total of 206.10 admissions. Of the 50 patients discharged with the highest PRISA scores (that is, with the highest likelihood of admission), none were admitted in the 48 hours after their original attendance. CONCLUSIONS: These results show that the PRISA is suitable as a measure of paediatric A&E department performance in the United Kingdom and it is highly promising as a future measure of quality.

Adolescent↗

PubMed2002

Paracetamol use in pregnancy and wheezing in early childhood.

BACKGROUND: We recently reported links between frequent paracetamol (acetaminophen) use and wheezing and asthma in adults and children, but data are lacking on possible effects of prenatal exposure on wheezing in early childhood. METHODS: In the population based Avon Longitudinal Study of Parents and Children (ALSPAC) women were asked twice during pregnancy (at 18-20 weeks and 32 weeks) about their usage of paracetamol and aspirin. Six months after birth, and at yearly intervals thereafter, mothers were asked about wheezing and eczema symptoms in their child. The effects of paracetamol and aspirin use in pregnancy on the risk in the offspring of wheezing at 30-42 months (n=9,400) and eczema at 18-30 months (n=10,216) and on their risk of different wheezing patterns (defined by presence or absence of wheezing at <6 months and at 30-42 months) were examined. RESULTS: Paracetamol was taken frequently (most days/daily) by only 1% of women. After controlling for potential confounders, frequent paracetamol use in late pregnancy (20-32 weeks), but not in early pregnancy (<18-20 weeks), was associated with an increased risk of wheezing in the offspring at 30-42 months (adjusted odds ratio (OR) compared with no use 2.10 (95% CI 1.30 to 3.41); p=0.003), particularly if wheezing started before 6 months (OR 2.34 (95% CI 1.24 to 4.40); p=0.008). Assuming a causal relation, only about 1% of wheezing at 30-42 months was attributable to this exposure. Frequent paracetamol use in pregnancy was not associated with an increased risk of eczema. Frequent aspirin use in pregnancy was associated with an increased risk of wheezing only at <6 months. CONCLUSIONS: Frequent use of paracetamol in late pregnancy may increase the risk of wheezing in the offspring, although such an effect could explain only about 1% of the population prevalence of wheezing in early childhood.

Acetaminophen↗

PubMed2001

Inhibition of angiogenesis and metastasis in two murine models by the matrix metalloproteinase inhibitor, BMS-275291.

BMS-275291 is an p.o. bioavailable, sulfhydryl-based matrix metalloproteinase (MMP) inhibitor currently in clinical development for the treatment of cancer. This inhibitor was designed to potently inhibit MMP activities while minimally affecting those of other metalloproteases (e.g., sheddases) involved in the release of cell-associated molecules such as tumor necrosis factor-alpha, tumor necrosis factor-alpha receptor, interleukin-6 receptor, or L-selectin. In vitro, BMS-275291 is a potent inhibitor (nM) of the activities of MMP-1, MMP-2, MMP-7, MMP-9, and MMP-14. BMS-275291 inhibits tumor growth in a B16BL6 model of experimental metastasis, and in this model, BMS-275291 treatment results in a dose-dependent reduction in the number of lung metastases compared with vehicle controls. BMS-275291 also inhibits angiogenesis in a murine angiogenesis model, where once daily treatment with BMS-275291 results in a dose-dependent inhibition of endothelial cell migration into s.c. implanted Matrigel plugs. Pharmacokinetic studies demonstrated that the plasma concentrations of parent BMS-275291 in mice exceeds the in vitro IC(50) values for MMP-1, MMP-2, MMP-7, MMP-9, and MMP-14 for at least 4 h after the administration of a therapeutic dose of BMS-275291. Taken together, these data demonstrate that BMS-275291 inhibits MMP activities that contribute to tumor metastasis and angiogenesis.

Animals↗

PubMed2001

Living anonymous kidney donation: what does the public think?

BACKGROUND: Health professionals are increasingly turning to living organ donation to augment cadaveric donation. Although living donation is currently performed with donors who are either genetically or emotionally related to the recipient, a 1997 British Columbia Transplant Society survey indicated that 32% of BC residents would be willing to donate a kidney, while alive, to a stranger (unpublished data). The goal of this study is to tap the public pulse about the living anonymous donor (LAD) by replicating and expanding the 1997 findings. METHODS: Five hundred BC residents completed a telephone survey including demographic information, questions about their organ donation behaviors and attitudes, and their willingness to donate a kidney, while alive, to particular individuals (child, spouse, parent, relative, friend, and stranger). To improve the methodological rigor of the 1997 study, an informed condition was added in the current study where participants learned about living donation before being asked about their willingness to donate. RESULTS: There were no differences among the 1997 results and the two conditions in the 2000 survey. Twenty-eight percent of participants in the uninformed condition and 29% of participants in the informed condition indicated that they would be willing to be LADs. LADs were more likely than self-reported non-donors to have registered as cadaveric donors and to endorse attitudes that were congruent with wanting to donate to a stranger. CONCLUSIONS: This study replicates the 1997 findings and increases confidence that a significant minority of British Columbians support living anonymous donation and that some would consider becoming LADs themselves.

Adolescent↗

PubMed2001

Long-term bone marrow cultures provide access to early lymphoid progenitors.

Long-term bone marrow cultures provide defined systems for studying and manipulating hematopoietic progenitors. Myeloid bone marrow cultures harbor early lymphoid progenitors; however, the nature and phenotype of these progenitors has not been investigated. Phenotypic and molecular markers associated with lymphopoiesis were used to characterize the lymphoid population maintained in these cultures. Cells within myeloid cultures expressed genes associated with lymphopoiesis but did not express the B cell-specific lambda5 gene. Flow cytometry demonstrated that cultures lacked cells expressing markers associated with B cell development. Furthermore, rearrangements of immunoglobulin heavy chain diversity (D) and joining (J(H)) gene segments were not detected in the myeloid cultures suggesting that these conditions support early B cell progenitors. Transferring myeloid cultures to conditions optimal for lymphopoiesis resulted in B cell development that temporally recapitulated events in the bone marrow. We also demonstrate that these lymphoid progenitors are targets for retroviral transduction. This study suggests that long-term cultures provide a useful system to access early lymphoid progenitors and study the events that regulate their differentiation.

Animals↗

PubMed2001

Ectopic expression of CCAAT/enhancer binding protein beta (C/EBPbeta) in long-term bone marrow cultures induces granulopoiesis and alters stromal cell function.

CCAAT/enhancer binding proteins (C/EBP) have been demonstrated to impact directly the development of multiple hematopoietic lineages. However, the role of C/EBPbeta in the differentiation of various hematopoietic lineages has not been thoroughly examined. We used primary bone marrow cultures to assess directly the ability of C/EBPbeta to influence myelopoiesis. Retroviral expression vectors were used to express C/EBPbeta ectopically in murine primary long-term bone marrow cultures. The differentiation potential of these cells was determined using hematopoietic colony assays and differential staining of cells within the cultures. Bone marrow cultures that overexpressed C/EBPbeta had fewer myeloid progenitors and a significant increase in the number of granulocytes. The ability of C/EBPbeta to alter hematopoiesis in vitro was dependent on the presence of the transcriptional activation domain because LIP, which lacks this functional domain, did not decrease the ability of bone marrow cultures to support myeloid progenitors. These data also show that C/EBPbeta influences hematopoiesis by altering stromal cell function rather than the intrinsic developmental potential of myeloid progenitor cells.

Animals↗

PubMed2001

Evaluation of the clinical efficacy of meloxicam in cats with painful locomotor disorders.

The ability of two non-steroidal anti-inflammatory drugs to modify the clinical manifestations of pain associated with locomotor disease was assessed. Sixty-nine cats with acute or chronic locomotor disorders were recruited from 14 first opinion UK veterinary practices and randomly allocated to one of two treatment groups. Group A received meloxicam drops (0.3 mg/kg orally on day 1 followed by 0.1 mg/kg daily for four more consecutive days) and group B received ketoprofen tablets (1.0 mg/kg orally once daily for five days). Each cat underwent a full clinical examination before treatment, 24 hours after initiation of treatment and 24 hours after completion of treatment. General clinical parameters (demeanour and feed intake) and specific locomotor parameters (weightbearing, lameness, local inflammation and pain on palpation) were scored using a discontinuous scale scoring system. The two groups did not differ in terms of age, weight, gender distribution or duration of clinical signs; nor did they differ in terms of general clinical or specific locomotor scores pretreatment. Both treatment regimens resulted in a significant improvement in demeanour, feed intake and weightbearing, and a significant reduction in lameness, pain on palpation and inflammation. No significant difference was observed between the two treatment groups with respect to any of the parameters measured and both treatments were associated with minimal observed side effects. Meloxicam and ketoprofen were found to be effective analgesics and well tolerated in cats with acute or chronic locomotor disorders when administered for short-term treatment (five days) in such cases. However, meloxicam was assessed to be significantly more palatable than ketoprofen.

Administration, Oral↗

PubMed2001

Endothelial cells enhance human immunodeficiency virus type 1 replication in macrophages through a C/EBP-dependent mechanism.

Macrophages are early targets of human immunodeficiency virus type 1 (HIV-1) infection and serve as potential reservoirs for long-term infection. Through inflammatory mediators and direct cell contact, infected macrophages interact with neighboring cell populations, such as the endothelium, which create a microenvironment favorable for HIV-1 replication. We hypothesize that the transcriptional activator C/EBPbeta is critical for macrophages to respond to endothelial cell-derived signals. We show that endothelial cells significantly enhance C/EBPbeta binding activity and HIV-1 replication in macrophages. This increase in HIV-1 transcription is due to cell-cell contact as well as the production of soluble factors, mediated in part by ICAM-1 and interleukin 6, respectively. Furthermore, C/EBP factors are necessary for endothelial cell-dependent activation of HIV-1 transcription in macrophages, and HIV-1 induction can be inhibited by a C/EBP dominant-negative protein. In addition, C/EBP binding sites are necessary for efficient LTR activity and HIV-1 replication in the presence of endothelial cells. Taken together, these results indicate that endothelial cells, through the activation of C/EBPbeta, provide a microenvironment that supports HIV-1 replication in monocytes/macrophages.

CCAAT-Enhancer-Binding Protein-beta↗

PubMed2001

Pre- and postnatal parental smoking and wheeze in infancy: cross cultural differences. Avon Study of Parents and Children (ALSPAC) Study Team, European Longitudinal Study of Pregnancy and Childhood (ELSPAC) Co-ordinating Centre.

In longitudinal cohort studies, the relationships between prenatal and postnatal tobacco smoke exposure and infant wheezing illnesses were compared in two geographically defined populations in Avon, UK and Brno and Znojmo in the South Moravian Region of the Czech Republic. Pregnant females living in defined regions and with expected dates of delivery between defined dates were recruited. Females completed self-report questionnaires during pregnancy and when their infant was 6 months old. For this analysis, responses to questions about smoking during pregnancy, environmental tobacco smoke (ETS) exposure and reported wheezing illnesses of infants at 6 months after birth were used. Odds ratios for wheeze in relation to the smoking variables were calculated with adjustment for potential confounding effects. The prevalence of smoking during pregnancy was higher in Avon (17.5%) than the Czech Republic (7.1%). Exposure of infants to ETS during the first 6 months after birth was also reported to be higher in Avon (35.5%) than the Czech Republic (9.7%). The prevalence of reported wheezing by 6 months of age was 21.4% in Avon and 10.3% in Brno and Znojmo. In Avon, there was a significant relationship between infant wheeze and maternal smoking during pregnancy (odds ratio (95% confidence interval) 1.30 (1.09-1.56), p=0.004) but not with environmental exposure after birth (1.11 (0.98-1.25)). In contrast, in Brno and Znojmo in the Czech Republic, there was a significant relationship between infant wheeze and ETS exposure (1.66 (1.17-2.36), p=0.04) but not with maternal smoking during pregnancy (0.99 (0.64-1.55)). This study demonstrated an apparent difference in the associations between prenatal and postnatal tobacco smoke exposure and infant wheezing illnesses in two populations with different smoking prevalence. The relationships were independent of a number of potential confounding variables that have been associated with infant wheezing. Possible explanations of these observations include dose-related effects of prenatal and postnatal tobacco smoke exposure of infants.

Adult↗

PubMed2000

A method for bronchoscopic evaluation of salivary aspiration in a disabled child.

Chronic aspiration is a cause of life-threatening respiratory complications and repeated hospital admissions, particularly in children with neurological disabilities. Determining the source of aspiration is important for optimizing treatment. This report describes a simple technique to demonstrate salivary aspiration during fibreoptic bronchoscopy. A child with a history of recurrent pneumonia was given methylene blue orally 2 h prior to fibreoptic bronchoscopy. Bronchoscopy was carried out through a laryngeal mask airway under inhalational anaesthesia. The stained saliva was seen to be pooling in the valleculae and then running down the trachea into the bronchi, confirming salivary aspiration.

Bronchoscopy↗