Biomedical subjects

M E Andrew

Publications and source records attributed to M E Andrew.

At least 19 recordsLinked to original sources

PubMed2006

A statistical test to determine the quality of accelerometer data.

Accelerometer data quality can be inadequate due to data corruption or to non-compliance of the subject with regard to study protocols. We propose a simple statistical test to determine if accelerometer data are of good quality and can be used for analysis or if the data are of poor quality and should be discarded. We tested several data evaluation methods using a group of 105 subjects who wore Motionlogger actigraphs (Ambulatory Monitoring, Inc.) over a 15 day period to assess sleep quality in a study of health outcomes associated with stress among police officers. Using leave-one-out cross-validation and calibration-testing methods of discrimination statistics, error rates for the methods ranged from 0.0167 to 0.4046. We found that the best method was to use the overall average distance between consecutive time points and the overall average mean amplitude of consecutive time points. These values gave us a classification error rate of 0.0167. The average distance between points is a measure of smoothness in the data, and the average mean amplitude between points gave an average reading. Both of these values were then normed to determine a final statistic, K, which was then compared to a cut-off value, K(C), to determine data quality.

Acceleration↗

PubMed2006

Molecular cloning and characterization of pig, cow and sheep MAdCAM-1 cDNA and the demonstration of cross-reactive epitopes amongst mammalian homologues.

Full-length cDNA clones for the pig, cow and sheep mucosal addressin cellular adhesion molecule (MAdCAM)-1 homologues were isolated from Peyer's patches by a combination of reverse transcription (RT)-polymerase chain reaction and 5' and 3' RACE strategies. Degenerate primers based on conserved amino acid (aa) sequences within the N-terminal immunoglobulin (Ig)-like domains of the human and rodent MAdCAM-1 molecules were used for initial sequencing of the Ig-like domains. MAdCAM-1 transcripts of 1425 bp, 1525 bp and 1510 bp obtained for the pig, cow and sheep contained an open-reading frame for proteins of 390, 424 and 418 aa, respectively. The pig and ruminant MAdCAM-1 had two N-terminal Ig-like domains, a mucin-like region and a third Ig-like domain found in rodent but not human MAdCAM-1. Antibodies raised against bacterially expressed N-terminal Ig-like domains of pig, human and sheep MAdCAM-1 demonstrated the existence of cross-reactive epitopes, raising the possibility of producing monoclonal antibodies which can be used as multi-species MAdCAM-1-targeting reagent for the development of mucosal vaccines.

Amino Acid Sequence↗

PubMed2005

Platelet aggregation in whole blood is a paradoxical predictor of ischaemic stroke: Caerphilly Prospective Study revisited.

The Caerphilly Prospective Study demonstrates a paradoxical association of increased ischaemic stroke risk with decreased whole blood adenosine diphosphate (ADP) induced platelet sensitivity. A reanalysis of this association examines whether other haematological indices and prevalent disease at baseline may explain this finding. There were 1506 men free of clinical cardiovascular disease at baseline, with 85 men manifesting a first ischaemic stroke event over 8.3 years of follow-up in this population-based prospective cohort study. Using two different approaches, the paradoxical findings are confirmed and associations are slightly stronger after accounting for red cell, platelet, and white cell indices. A U-shaped relation of stroke with platelet count is noted. These findings are consistent with the existence of sub-clinical endothelial disease and compensatory mechanisms down-regulating ADP-induced aggregation sensitivity. They support an allostasis model of causality for understanding the paradox. A public health approach to prevention could have measurable impact if intervention strategies can be developed to alter early stages of disease appropriate to such mechanisms of causation.

Adenosine Diphosphate↗

PubMed2001

A prime-boost vaccination strategy using naked DNA followed by recombinant porcine adenovirus protects pigs from classical swine fever.

Weaned pigs (6-week-old) and 7-day-old pre-weaned piglets were vaccinated with naked plasmid DNA expressing the gp55/E2 gene from classical swine fever virus (CSFV). Both groups of pigs were then given a booster dose of recombinant porcine adenovirus expressing the gp55 gene (rPAV-gp55). Following challenge with CSFV, 100% of weaned pigs and 75% pre-weaned piglets were protected from disease. Weaned pigs given a single dose of rPAV-gp55 were also protected, but showed a slight increase in temperature immediately post-challenge. However, weaned animals given a DNA prime before rPAV-gp55 showed no fluctuation in body temperature following challenge and no pathology in spleen or lymph nodes upon post-mortem. In addition, no CSFV could be re-isolated from the rPAV vaccinated group and from only one pig in the prime-boost group following challenge, suggesting that both vaccination regimes have the potential to reduce or prevent virus shedding following experimental challenge.

Adenoviridae↗

PubMed2001

Acquired activated protein C resistance is associated with lupus anticoagulants and thrombotic events in pediatric patients with systemic lupus erythematosus.

Acquired activated protein C resistance (APCR) has been hypothesized as a possible mechanism by which antiphospholipid antibodies (APLAs) cause thrombotic events (TEs). However, available evidence for an association of acquired APCR with APLAs is limited. More importantly, an association of acquired APCR with TEs has not been demonstrated. The objective of the study was to determine, in pediatric patients with systemic lupus erythematosus (SLE), whether (1) acquired APCR is associated with the presence of APLAs, (2) APCR is associated with TEs, and (3) there is an interaction between APCR and APLAs in association with TEs. A cross-sectional cohort study of 59 consecutive, nonselected children with SLE was conducted. Primary clinical outcomes were symptomatic TEs, confirmed by objective radiographic tests. Laboratory testing included lupus anticoagulants (LAs), anticardiolipin antibodies (ACLAs), APC ratio, protein S, protein C, and factor V Leiden. The results revealed that TEs occurred in 10 (17%) of 59 patients. Acquired APCR was present in 18 (31%) of 58 patients. Acquired APCR was significantly associated with the presence of LAs but not ACLAs. Acquired APCR was also significantly associated with TEs. There was significant interaction between APCR and LAs in the association with TEs. Presence of both APCR and LAs was associated with the highest risk of a TE. Protein S and protein C concentrations were not associated with the presence of APLAs, APCR, or TEs. Presence of acquired APCR is a marker identifying LA-positive patients at high risk of TEs. Acquired APCR may reflect interference of LAs with the protein C pathway that may represent a mechanism of LA-associated TEs. (Blood. 2001;97:844-849)

Activated Protein C Resistance↗

PubMed2001

Rapid dissemination of intramuscularly inoculated DNA vaccines.

Deoxyribonucleic acid (DNA) vaccination offers the prospect of novel, safe vaccines that can stimulate cell-mediated immunity as well as antibody. An understanding of how and where transfection occurs in vivo will assist strategies to enhance their efficacy. Plasmid DNA encoding for the expression of firefly luciferase was injected intramuscularly into sheep. The DNA was rapidly disseminated and could be detected in efferent lymph within 5 min. At the earliest time that cells were tested separately from lymph plasma (1 h), DNA was found to be present in both the lymph plasma and within lymph cells. Although plasmid DNA could be detected intracellularly in lymph and in muscle tissue at the site of inoculation, no luciferase gene expression could be detected. The results suggest that, in addition to the internalization of plasmid DNA, other factors may limit gene expression, possibly the rate of DNA migration into the nucleus.

Animals↗

PubMed2001

Thromboembolic disease and antithrombotic therapy in newborns.

This update uses an evidence based approach to analyze and present the epidemiology of neonatal thrombosis, etiologies, currently used techniques for diagnosis with their limitations, and current therapeutic approaches. In addition, the approaches to both prevention and optimal therapies are discussed. In Section I Dr. Paul Monagle addresses the epidemiology of neonatal thrombosis outside of the central nervous system in both arterial and venous locations, and those that occur in utero. The specific contributions of catheters and congenital prothrombotic disorders are delineated. Dr. Monagle also describes currently used techniques for the diagnosis of thrombotic events as well as their limitations and the current therapeutic approaches. In Section II, Dr. Gabrielle deVeber reviews the epidemiology of neonatal thrombosis within the central nervous system, in both arterial and venous locations and those that occur in utero. The neurological presentation, risk factors including congenital prothrombotic disorders, anatomical distribution, diagnostic tests, use of antithrombotic therapy and neurologic outcome of neonates with either sinovenous thrombosis or arterial ischemic stroke are discussed. In Section III, Dr. Anthony Chan reviews the current approaches to the prevention and treatment of neonatal thrombosis. Information on the differences in the response of neonates compared to adults to antithrombotic therapy and new approaches to the prevention and treatment of thrombosis in neonates are emphasized.

Female↗

PubMed2000

The immune response to a polyoma virus replicon-based DNA vaccine.

DNA vaccination has proven to be effective against a number of tumours and microbial diseases. As DNA vaccines are unable to replicate, plasmid copy number per cell is dependent on in vivo transfection efficiency, which is usually quite low. Consequently, immune responses generated are likely to be sub-optimal due to low antigen expression levels in transfected cells. During this study, replicating DNA vaccines delivered intra-epidermally by gene gun, were assessed for their ability to more efficiently generate immune responses in mice. The data demonstrate that, using a polyoma virus-based system of replication, 10-fold less DNA expressing the haemagglutinin gene of influenza virus, was required to stimulate a humoral immune response, compared to an equivalent non-replicating vaccine. This observation suggests that the use of replicating DNA vaccines in some delivery systems may enhance the effectiveness of immune responses.

Animals↗

PubMed2000

Protection of pigs against classical swine fever with DNA-delivered gp55.

Classical swine fever virus causes significant mortality and morbidity in commercial piggeries in many countries in Europe and Asia. The protective antigen, gp55, is highly conformation-dependent and thus killed virus or bacterially produced proteins are not protective. This report demonstrates that DNA vaccination with the gene encoding gp55 can provide protective immunity with inoculation of two doses of 25 microg DNA or a single shot of 200 microg. Furthermore, the DNA can be delivered intramuscularly or by a simple spring-loaded needleless inoculator. In addition it is shown that inoculation of the DNA at a single site conveys the same level of immunity as division of the dose between two sites.

Animals↗

PubMed2000

Insertion sites for recombinant vaccinia virus construction: effects on expression of a foreign protein.

The expression of antigens or other molecules from recombinant vaccinia viruses requires the insertion of coding sequence at specific sites in the viral genome. Here we investigate the influence of two different sites on the level of protein expressed during a viral infection. The level of immune response in mice to vaccinia virus-expressed murine interleukin 2 (IL-2) or IL-4 varied depending on whether the coding sequence was inserted into the vaccinia virus thymidine kinase (tk) gene or into the HindIII F fragment of the viral genome where herpes simplex virus (HSV) tk was used as a selectable marker. In each case the intensity of the response was greater when the relevant gene was expressed from the HindIII F insertion site. In order to quantify these differences a series of recombinant viruses expressing luciferase was constructed. Luciferase activity from coding sequence inserted into the HindIII F fragment was significantly higher than that from the tk gene insertion, provided HSV tk(+) constructs were compared. Insertion of a marker gene (HSV tk) into the HindIII F site with disruption of the F7L open reading frame led to a reduced level of luciferase expressed from the tk insert, despite more than 45 kb of intervening sequence. In mice, luciferase expression was higher from the HindIII F inserted gene than from the tk insert in both lungs and ovaries.

Animals↗

PubMed1999

Cytokine therapy: a natural alternative for disease control.

Disease control in food production animals is normally mediated through the use of vaccines, chemicals and antibiotics. However, the extensive use of antibiotics and chemicals in livestock has resulted in environmental and human health concerns, particularly with regard to the emergence of drug-resistant bacteria in the food chain. In fact, the World Health Organisation (WHO) has now urged meat producers to use environmentally-friendly alternative methods to control disease. Cytokines, as natural mediators of the immune response, offer exciting alternatives to conventional therapeutics. The utilisation of cytokines is becoming more feasible with the recent cloning of a number of cytokine genes. Since the chicken's immune system is similar to that of mammals, they offer an attractive model system with which to study the effectiveness of cytokine therapy in the control of disease in intensive livestock. In this report we will review our recent studies on the therapeutic potential of chicken interferon gamma (ChIFN-gamma) as a vaccine adjuvant and a growth promoter.

Adjuvants, Immunologic↗

PubMed1999

The ovine cytotoxic T lymphocyte responses to bluetongue virus.

This study uses recombinant vaccinia viruses expressing truncated or entire bluetongue virus (BTV) proteins to map the location of epitopes recognized by cytotoxic T lymphocytes (CTL) from Australian merino sheep. The non-structural protein, NS1, was recognised by CTL from all sheep, while VP2, VP3, VP5 and VP7 were recognised by CTL from only some sheep. The remaining proteins (except for VP1, which was not tested) did not contain CTL epitopes. When truncated genes were used to map the location of CTL epitopes, it was found that sheep often have CTL that recognise more than one epitope in NS1 or VP2. Overall there was considerable diversity in the CTL recognition patterns in the sheep tested.

Animals↗

PubMed1998

Venous thromboembolic events in pediatric patients. Diagnosis and management.

Venous thromboembolism is a rapidly increasing secondary complication in children being treated for serious, life-threatening, primary diseases. Most current management guidelines and recommendations for imaging techniques have been extrapolated from the results of trials in adults. This may be less than optimal for children as there are important differences. The purpose of this article is to summarize the information on venous thromboembolism in children, and offer some guidelines for diagnosis, prophylaxis, and therapeutic intervention based on the best available evidence.

Adolescent↗

PubMed1997

Effect of heparin loading during congenital heart operation on thrombin generation and blood loss.

BACKGROUND: The heparin protocols used during cardiopulmonary bypass (CPB) in children undergoing surgical repair for congenital heart disease are extrapolated from adult data. Studies are needed that assess the optimal heparin dosing in these children, whose heparin clearance is increased compared with that in adults. METHODS: We assessed the effects of two commonly used doses of heparin in the prime solution at the start of CPB operation on plasma heparin levels, on thrombin production (thrombin-antithrombin III complexes, prothrombin fragment 1 + 2, D-dimer, and antithrombin III), and on the risk of hemorrhage. Before CPB, 48 children with congenital heart disease received heparin intravenously in a loading dose of 300 U/kg, followed by either 1 U/mL of heparin in the prime (low-dose group: 22 patients-acyanotic, 9; cyanotic, 13) or 3 U/mL of heparin in the prime (group: high-dose, 26 patients-acyanotic, 15; cyanotic, 11). RESULTS: In all patients, CPB resulted in the generation of thrombin. The duration of CPB was a significant covariate factor for heparin levels (p = 0.002), thrombin production (p < 0.001), and postoperative blood loss (p < 0.001). In the patients in the high-dose group, the total heparin dose and the plasma heparin levels were higher (p = 0.0005 and 0.005, respectively) and the D-dimer levels tended to be lower (p = 0.06). The postoperative blood loss was higher in the cyanotic patients (p = 0.02; both high-dose and low-dose groups), with 2 cyanotic patients (1 in low-dose group, 1 in high-dose group) requiring reoperation, one of whom subsequently died. The increased heparin dose had no significant effect on the rate or volume of postoperative blood loss. CONCLUSIONS: Increasing the heparin dose in the prime solution from 1 to 3 U/mL increased the plasma heparin levels and showed a trend toward reducing the postoperative laboratory values indicative of fibrinolysis. Thrombin generation during CPB and the incidence of postoperative hemorrhage were not significantly altered. Larger randomized trials are needed to determine the optimal heparin-dosing regimen in patients with congenital heart disease.

Adolescent↗

PubMed1997

Antibody responses and protective immunity to recombinant vaccinia virus-expressed bluetongue virus antigens.

The role of individual viral proteins in the immune response to bluetongue virus (BTV) is not clearly understood. To investigate the contributions of the outer capsid proteins, VP2 and VP5, and possible interactions between them, these proteins were expressed from recombinant vaccinia viruses either as individual proteins or together in double recombinants, or with the core protein VP7 in a triple recombinant. Comparison of the immunogenicity of the vaccinia expressed proteins with BTV expressed proteins was carried out by inoculation of rabbits and sheep. Each of the recombinants was capable of stimulating an anti-BTV antibody response, although there was a wide range in the level of response between animals and species. Vaccinia-expressed VP2 was poorly immunogenic, particularly in rabbits. VP5, on the whole, stimulated higher ELISA titers in rabbits and sheep and in some animals in both species was able to stimulate virus neutralizing antibodies. When the protective efficacy of VP2 and VP5 was tested in sheep, vaccinia-expressed VP2, VP5 and VP2 + VP5 were protective, with the most consistent protection being in groups immunized with both proteins.

Animals↗

PubMed1997

Incidence and natural history of chemically defined varicella-zoster virus hepatitis in children and adolescents.

Of 786 children and adolescents enrolled in a multicenter trial of acyclovir for chickenpox, 27 (3.4%) met the case definition of varicella-zoster virus (VZV) hepatitis (serum aspartate aminotransferase level > or = 100 U/l). The clinical and cutaneous manifestations of chickenpox in the 15 placebo recipients with this complication did not differ significantly from those in 45 matched controls (p > 0.05), indicating that liver involvement by VZV is not a consequence of more extensive disease. Although acyclovir modified the course of chickenpox overall, it did not prevent VZV hepatitis; that is, the proportions of affected subjects with liver involvement postenrollment did not differ significantly between the drug and placebo recipients (50% vs 80%, p > 0.05). Serum aspartate aminotransferase levels that were elevated on day 4 postenrollment had returned to normal (< or = 60 U/l) by day 28 in 88% of the placebo group and in 83% of the drug-treated group. With 2 exceptions, all values were normal by 88 days postenrollment. We conclude that chemically defined VZV hepatitis is an infrequent, self-limiting complication of chickenpox in otherwise healthy children and adolescents.

Acyclovir↗

PubMed1997

Twins and preterm labor.

OBJECTIVE: To assess the effect of home uterine contraction assessment (HUCA) in twin pregnancies with preterm labor (PTL) at < 24 weeks' gestation. STUDY DESIGN: In this retrospective, analytic study, patients were stratified by whether HUCA had been prescribed before or after diagnosis of PTL. The main outcomes studied were time of PTL diagnosis and delivery as well as birth weight and need for neonatal intensive care unit (NICU) admission. In 63 patients, 32 were prescribed HUCA after PTL had been arrested at < 24 weeks (group I). Thirty-one women had HUCA prescribed at 20 weeks' gestational age and then developed PTL at < 24 weeks (group II). RESULTS: Labor was diagnosed at similar times in both groups (22.8 vs 23.4 weeks), but delivery was earlier in group I (27.6 weeks vs. 34.7 weeks) than in group II. The birth weight in group I was less (918 +/- 255 g), and of the 64 infants, 55 required NICU admission as compared to 2,340 +/- 525 g and 11 of 62 infants (P < .0001, .0001) in group II, respectively. CONCLUSION: Women with twin gestations and the diagnosis of PTL prior to 24 weeks deliver later in gestation, and their infants weigh more and have fewer NICU admissions if intensive prenatal surveillance is prescribed prior to the onset of labor.

Adult↗

PubMed1996

The clinical efficacy of oral tocolytic therapy.

OBJECTIVE: Our purpose was to determine whether maintenance oral tocolytic therapy after preterm labor stabilization decreases uterine activity, reduces the rate of recurrent preterm labor and subsequent preterm birth, or improves neonatal outcome. STUDY DESIGN: Women with documented idiopathic preterm labor stabilized with acute tocolytic therapy were randomized to three groups: placebo, terbutaline 5 mg, or magnesium chloride 128 mg, all given orally every 4 hours. Patients and providers were blinded to group assignment. All subjects were enrolled in a comprehensive system of preterm birth prevention that included preterm labor education, weekly clinic visits, home uterine contraction assessment, daily phone contact, and 24-hour perinatal nurse access. RESULTS: Of the 248 patients who were randomized, 39 were delivered before discharge and 4 were lost to follow-up, leaving 205 for final analysis: 68 placebo, 72 terbutaline, and 65 magnesium. The terbutaline group had significantly more side effects than the placebo group did. All groups had otherwise similar perinatal outcomes when confounding variables were controlled for. Overall, the three groups had a preterm birth rate < 37 weeks of 55.6% delivery, < 34 weeks of 15.6%, a 20.4% rate of newborn intensive care unit admission, and a mean neonatal length of stay of 6.3 days. CONCLUSIONS: Maintenance oral tocolytic therapy did not decrease uterine activity, reduce the rate of recurrent preterm labor or preterm birth, or improve perinatal outcome. Overall improvement in perinatal outcome may be achieved with a comprehensive program of preterm birth prevention without the use of maintenance oral tocolytic therapy.

Administration, Oral↗