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Biomedical subjects

L Barnett

Publications and source records attributed to L Barnett.

At least 19 recordsLinked to original sources
PubMed2006

Economic analysis of a community-based falls prevention program.

OBJECTIVES: To undertake a cost-benefit analysis of 'Stay on Your Feet', a community-based falls prevention program targeting older people at all levels of risk in New South Wales, Australia. Hospital separations were monitored in the intervention region, a control region and for the state of New South Wales as a whole. Changing admission patterns over the intervention period were used to assess the impact of the program. METHODS: Cost-benefit analysis compared the costs of the program with two estimates of savings from avoided hospital admissions. The first compared the cost of hospital admissions in the intervention region to a control region of similar demographics, while the second compared hospital utilization in the intervention region with the state of New South Wales as a whole using falls-related hospital diagnosis related group (DRG) codes. RESULTS: The total direct costs of the program were estimated at A dollars 781,829. Both methods identified clear overall net benefits ranging from A dollars 5.4 million for avoided hospitalizations alone to A dollars 16.9 million for all avoided direct and indirect costs. The confidence intervals around these estimates were small. The average overall benefit to cost ratio for the intervention as a whole was 20.6:1. CONCLUSIONS: These findings suggest that well-designed community-based interventions targeting falls prevention among older people are highly cost effective and a wise investment for all levels of government. The models used are conservative and are likely to underestimate the real benefit of the intervention, which may have lasted for some time beyond the life of the program.

Accidental Falls↗
PubMed2001

The small muscle-specific protein Csl modifies cell shape and promotes myocyte fusion in an insulin-like growth factor 1-dependent manner.

We have isolated a murine cDNA encoding a 9-kD protein, Chisel (Csl), in a screen for transcriptional targets of the cardiac homeodomain factor Nkx2-5. Csl transcripts were detected in atria and ventricles of the heart and in all skeletal muscles and smooth muscles of the stomach and pulmonary veins. Csl protein was distributed throughout the cytoplasm in fetal muscles, although costameric and M-line localization to the muscle cytoskeleton became obvious after further maturation. Targeted disruption of Csl showed no overt muscle phenotype. However, ectopic expression in C2C12 myoblasts induced formation of lamellipodia in which Csl protein became tethered to membrane ruffles. Migration of these cells was retarded in a monolayer wound repair assay. Csl-expressing myoblasts differentiated and fused normally, although in the presence of insulin-like growth factor (IGF)-1 they showed dramatically enhanced fusion, leading to formation of large dysmorphogenic "myosacs." The activities of transcription factors nuclear factor of activated T cells (NFAT) and myocyte enhancer-binding factor (MEF)2, were also enhanced in an IGF-1 signaling-dependent manner. The dynamic cytoskeletal localization of Csl and its dominant effects on cell shape and behavior and transcription factor activity suggest that Csl plays a role in the regulatory network through which muscle cells coordinate their structural and functional states during growth, adaptation, and repair.

Aging↗
PubMed2001

Active school playgrounds-myth or reality? Results of the "move it groove it" project.

BACKGROUND: School playgrounds during break times provide potential opportunities for children to be active during the school day. However, there is limited research on how active children really are during these breaks. METHODS: The CAST (Children's Activity Scanning Tool) instrument was developed, validated, and used to assess the percentages of children engaged in moderate to vigorous physical activity (MVPA) and vigorous physical activity (VPA-a subset of MVPA) in 18 primary schools (children ages 5-12) in rural Australia. Related environmental factors were also measured. RESULTS: For a school of median size (200 students), 51.4% of boys and 41.6% of girls were engaged in MVPA while 14.7% of boys and 9.4% of girls were engaged in VPA. Levels of engagement in MVPA and VPA were significantly higher during lunch periods than during recess. MVPA and VPA engagement in smaller schools was significantly higher than in larger schools. CONCLUSIONS: With growing concern about children's physical activity (PA), school playgrounds offer an opportunity to increase children's MVPA engagement especially among girls. Consideration may be given to the lengthening of recess periods in order to increase PA levels. More research is needed to investigate factors affecting PA levels in larger schools.

Child↗
PubMed2001

Mediated computer search services relative to instruction services: a survey of one health sciences library.

To assess the quality and usefulness of one health sciences library's mediated computer search service, a survey was undertaken to determine satisfaction rates, why users do or do not use the service, and how useful the service is perceived to be in comparison to instructional service. Satisfaction rates were high, with users indicating librarian expertise and time/cost savings as the main reasons for using the service. Non-users indicated that they preferred to do their own searching, and many were unaware of the service. Though a majority of respondents do not currently use the service, surprisingly a majority of respondents placed significant value on the mediated search service in relation to instruction.

Attitude to Computers↗
PubMed2001

Repeat use of emergency contraception: How frequent is it?

OBJECTIVE: To measure the level of repeat use of emergency contraception (EC) in family planning clinics (FPCs) in North and East Devon. DESIGN: An audit of repeat use of EC was carried out in seven FPCs, in parallel with a client survey. All women seeking EC in the study period were included (n = 572). RESULTS: Nearly 70% of women had 'ever' used EC prior to the study visit; over half had previously used EC in the year of the study; a quarter had previously used EC three or more times in the same period. Teenagers were more likely to have previously used EC in the study year, but half of all repeat users were aged 20 and older. Asked why EC was needed today, most women reported current use of regular contraception, but almost a quarter had had unprotected sex, and half reported a condom mishap. CONCLUSIONS: These results show frequent repeat use of EC and do not support recent research based on general practice records, which suggests that repeat use is rare. If EC users use multiple sources of EC, or prefer alternative sources, repeat use of EC will be underestimated if calculated using general practitioner (GP) records alone.

Adolescent↗
PubMed2001

Contact dermatitis treated with new topical products: a case study.

Contact dermatitis, an inflammatory response of the skin to an irritant or an allergen, can affect hospital staff. Most clinicians are routinely exposed to irritants such as latex, detergents, and chemicals. Treatment with topical corticosteroids and avoidance of suspect irritants usually resolves the dermatitis. A case study is presented of a licensed practical nurse who developed persistent contact dermatitis. The dermatitis did not resolve with 15 months of traditional treatments. Only after 3 months of treatment with two investigational topical products, which are now available to the public, was the dermatitis resolved and complete healing achieved. This case study discusses the new products and traditional treatment products used and presents results of irritant specificity testing and a series of photographs documenting resolution and healing.

Administration, Cutaneous↗
PubMed2000

Giant cyclophanes built from polyphenyl aromatic substructures

Two very large cyclophanes (3, C(132)H(92)O(8)S(4); 4, C(172)H(120)O(8)S(4)) were prepared by means of short syntheses ( approximately 5 steps) from commercial starting materials. In each of these cyclophanes, two octaphenylnaphthalene subunits or two 1, 3-bis(pentaphenylphenyl)benzene subunits were tethered to form the final macrocycle. X-ray analysis of 3 shows it to have a collapsed conformation, but molecules of 4 have large central cavities which are aligned in the crystal to form wide, solvent-containing channels.

Journal Article↗
PubMed2000

Cardiac septal and valvular dysmorphogenesis in mice heterozygous for mutations in the homeobox gene Nkx2-5.

Heterozygous mutations in the cardiac homeobox gene, NKX2-5, underlie familial cases of atrial septal defect (ASD) with severe atrioventricular conduction block. In this study, mice heterozygous for Nkx2-5-null alleles were assessed for analogous defects. Although ASD occurred only rarely, atrial septal dysmorphogenesis was evident as increased frequencies of patent foramen ovale and septal aneurysm, and decreased length of the septum primum flap valve. These parameters were compounded by genetic background effects, and in the 129/Sv strain, septal dysmorphogenesis bordered on ASD in 17% of Nkx2-5 heterozygotes. In a proportion of neonatal heterozygotes, as well as in adults with ASD, we found that the size of the foramen ovale was significantly enlarged and altered in shape, potentially exposing the normally thin septum primum to excessive hemodynamic forces. Therefore, defective morphogenesis of the septum secundum may be one contributing factor in the generation of patent foramen ovale, septal aneurysm, and certain ASDs. Mild prolongation of P-R interval in females and an increased frequency of stenotic bicuspid aortic valves were also features of the Nkx2-5 heterozygous phenotype. Our data demonstrate that the complex effects of Nkx2-5 haploinsufficiency in mice are weaker but convergent with those in humans. As in the mouse, the phenotype of human NKX2-5 mutations may be modulated by interacting alleles.

Alleles↗
PubMed2000

Homeodomain factor Nkx2-3 controls regional expression of leukocyte homing coreceptor MAdCAM-1 in specialized endothelial cells of the viscera.

Regulated emigration of blood-borne leukocytes plays a defining role in lymphoid organ development, immune surveillance, and inflammatory responses. We report here that mice deficient in the homeobox gene Nkx2-3, expressed in developing visceral mesoderm, show a complex intestinal malabsorption phenotype and striking abnormalities of gut-associated lymphoid tissue and spleen suggestive of deranged leukocyte homing. Mutant Peyer's patches were reduced in number and size, intestinal villi contained few IgA(+) plasma cells, and mutant spleens were small and often atrophic, showing fused periarterial lymphoid sheaths, partially merged T and B cell zones, an absent marginal zone, and a dearth of macrophages in red pulp. Semiquantitative RT-PCR analysis and immunohistochemistry revealed down-regulation of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in endothelial cells in which Nkx2-3 is normally expressed. MAdCAM-1 is a member of the immunoglobulin superfamily, acting as an endothelial cell ligand for leukocyte homing receptors L-selectin and alpha4beta7 integrin. Our data suggest a role for a homeodomain factor in establishing the developmental and positional cues in endothelia that regulate leukocyte homing through local control of cellular adhesion and identify MAdCAM-1 as a candidate target gene of Nkx2-3.

Animals↗
PubMed2000

Longitudinal monitoring of immune reconstitution by CDR3 size spectratyping after T-cell-depleted allogeneic bone marrow transplant and the effect of donor lymphocyte infusions on T-cell repertoire.

Delayed immune reconstitution after allogeneic bone marrow transplantation (BMT) with associated infection is a major cause of morbidity and mortality. We used third complementarity region (CDR3) size spectratyping as a tool for monitoring T-cell repertoire reconstitution in 19 patients over a median time of 40 months after T-cell-depleted allogeneic BMT for chronic myeloid leukemia (CML). Furthermore, the effect of donor lymphocyte infusions (DLI) for the treatment of relapse in 18 of the 19 patients was analyzed. All BMT recipients had irregular spectratypes in the first 3- to -6 months after transplant. These evolved to more normal patterns by 12 months after transplant and continued to improve thereafter. In approximately a third of the patients, it took 2 to 3 years for all spectratypes to normalize, whereas in the other two thirds, some abnormal spectratypes persisted even after several years. In 9 patients, there was no immediate change in the CDR3 size profiles after DLI. In 3 patients, spectratypes improved slightly after DLI, whereas in 6 patients, spectratypes became more restricted and irregular. Overall, T-cell spectratypes in BMT patients were characterized by instability over time and in patients with graft-versus-host disease (GVHD), this was even more exaggerated. Several factors, such as pre-BMT conditioning, T-cell depletion of the donor marrow, loss of thymic function in adults, exposure to infectious agents, GVHD, and immunosuppressive treatment, are likely contributors to the delay in T-cell-repertoire reconstitution. (Blood. 2000;95:3990-3995)

Adolescent↗
PubMed2000

Targeted insertion of a lacZ reporter gene into the mouse Cer1 locus reveals complex and dynamic expression during embryogenesis.

The mouse Cer1 (mCer1, Cer-l, Cerr1) gene encodes one member of a family of cytokines structurally and functionally related to the Xenopus head-inducing factor, Cerberus (xCer). We generated a mouse line in which the Cer1 gene was inactivated by replacing the first coding exon with a lacZ reporter gene. Mice homozygous for this allele (Cer1(lacZ)) showed no apparent perturbation of embryogenesis or later development. However, the lacZ reporter revealed a number of hitherto uncharacterised sites of Cer1 expression in late fetal and adult tissues. Preliminary analysis suggests that Cer1 is not essential for their morphogenesis, differentiation, or homeostasis.

Animals↗
PubMed2000

Review of leptospirosis notifications in Queensland and Australia: January 1998-June 1999.

The World Health Organization/Food and Agricultural Organization Collaborating Centre for Reference and Research on Leptospirosis, Western Pacific Region, accredited since 1958, is part of Queensland Health Scientific Services, which provide tertiary level support in epidemiology, surveillance, training and diagnosis for hospitals and pathology laboratories across the State. Databases for leptospirosis on a global, Australian and State-wide basis are maintained on site and support public health authorities in Australia, WHO and the International Leptospirosis Society. Queensland data collated and analysed from leptospirosis questionnaires, and a brief overview of Australian data based on questionnaire responses for notified cases from 1998 to June 1999, are summarised. The increase in leptospirosis notifications (77%) during 1998 possibly signalled greater awareness of the disease by clinicians. There was a significant increase in leptospirosis notifications for children and students and a high rate of hospitalisation of cases. An outbreak in North Queensland during the first half of 1999 resulted in 184 notifications with over 50% of cases hospitalised. Polymorphic presentation of the disease with severe pulmonary haemorrhage is associated in particular with the serovar australis. Serovar zanoni continues to be a major cause of severe clinical leptospirosis. Several cases were diagnosed in tourists. One of these cases presented with severe respiratory distress and required 14 days in hospital.

Adult↗
PubMed1999

Mutagenesis of a single AT basepair in mice transgenic for PhiX174 am3, cs70. II. Brain.

Most cell divisions in the mouse brain have ceased by 14 days after birth. Therefore, spontaneous mutations that occur in brain cells can be assumed to be fixed by replication during brain development. Spontaneous and ethylnitrosourea (ENU)-induced reverse mutations at a single AT base pair were measured in brain tissue by using mice transgenic for PhiX174 am3, cs70. The line (am54) has 50 PhiX genomes per haploid genome integrated in a tandem array and is maintained by random breeding on a C57BL/6 background. For mutagenesis studies, homozygous am54 males were mated to non-transgenic C57BL6/J females. Four-day old offspring from this cross were treated with 50 mg/kg ENU and were euthanized at 68-80 days of age. The ENU-treated animals had a significantly higher frequency of am3 revertants in brain than did concurrent controls. In a second experiment, hemizygous male offspring (85 to 94 days old) were treated with 150 mg/kg ENU and euthanized at various post-injection intervals (3, 10 and 110 days). The revertant frequencies 3 and 10 days after treatment were not significantly different from control values. At the 110 days post-injection interval, however, the average revertant frequency in the treated group was significantly lower than controls. In a second study animals were euthanized 3, 10 and 74 days after treatment. Two groups (3 and 74 days post-injection) also showed a significant decrease in the revertant frequency as compared to controls. Additional sets of adult animals were treated with 50 and 150 mg/kg ENU and were euthanized 195 to 201 days after treatment. The average revertant frequency of the animals that were treated with 50 or 150 mg/kg ENU was not significantly different from the control value. Thus, although an increase in mutant frequency is detected in the PhiX174 system when neonatal mice are treated with ENU, treatment of mature mice with ENU did not result in an increase in the mutant frequency. Moreover, under certain conditions, ENU-produced a significantly lower mutant frequency than was observed in the control animals. This decrease in the revertant frequency among the treated animals was likely due to selective killing of cells with a higher spontaneous revertant frequency than cells with lower frequency.

Animals↗
PubMed1998

Characterization of hematopoietic progenitor cells that express the transcription factor SCL, using a lacZ "knock-in" strategy.

Gene targeting experiments have demonstrated that the transcription factor SCL is essential for primitive and definitive hematopoiesis in the mouse. To study the functional properties of hematopoietic cells expressing SCL, we have generated mutant mice (SCLlacZ/w) in which the Escherichia coli lacZ reporter gene has been "knocked in" to the SCL locus, thereby linking beta-galactosidase expression to transcription from the SCL promoter. Bone marrow cells from heterozygous SCLlacZ/w mice were sorted into fractions expressing high, intermediate and low levels of beta-galactosidase (designated lacZhigh, lacZint, and lacZneg). Cells that were lacZhigh or lacZint were enriched for day 12 spleen colony-forming units and myeloid and erythroid colony-forming cells (CFCs). These fractions included >99% of the erythroid and >90% of the myeloid CFCs. Culture of sorted bone marrow populations on stromal cells secreting interleukin-7 or in fetal thymic organ cultures showed that B and T lymphoid progenitors were also present in the lacZhigh and lacZint fractions. These data provide a functional correlation between SCL expression and colony-forming ability in immature hematopoietic cells. Our data also suggested that expression of SCL was transient and confined to hematopoietic stem and/or progenitor cells, because the differentiated progeny of most lineages (except the erythroid) were beta-galactosidase-negative.

Animals↗
PubMed1998

Differential growth patterns in SCID mice of patient-derived chronic myelogenous leukemias.

The development of an in vivo model for the study of CML would be of significant importance in studying its biological behavior and developing novel therapeutic strategies. We examined the ability of human leukemic cells derived from patients in either chronic (CP), accelerated (AP) or blast phase (BP) CML to grow and disseminate in CB17-SCID mice by subcutaneous (s.c.) inoculation without conditioning treatment or administration of cytokines. Additionally, samples derived from patients with CP-CML were injected s.c. into CB17-SCID mice treated with anti-Asialo GM1 (an anti-NK cell antibody) and NOD-SCID mice (absent NK cell activity) to study the potential role of NK cell-mediated anti-leukemic activity in preventing the propagation of CP-CML cells. We observed a significant differential growth pattern of CML cells in the mice such that BP-CML grew rapidly as s.c. tumors and disseminated, while AP-CML or CP-CML cells grew temporarily as small nodules that spontaneously regressed and did not disseminate. This differential growth pattern suggests possible important biological differences. Furthermore, no significant difference in s.c. growth or dissemination of CP-CML samples derived from newly diagnosed patients in untreated CB17-SCID mice and CB-17 SCID mice treated with Anti-Asialo GM1 and NOD-SCID mice occurred, suggesting that factors other than NK cell anti-leukemic activity may be important.

Adolescent↗
PubMed1998

Tissue hyperplasia and enhanced T-cell signalling via ZAP-70 in c-Cbl-deficient mice.

The c-Cbl protein is tyrosine phosphorylated and forms complexes with a wide range of signalling partners in response to various growth factors. How c-Cbl interacts with proteins, such as Grb2, phosphatidylinositol 3-kinase, and phosphorylated receptors, is well understood, but its role in these complexes is unclear. Recently, the Caenorhabditis elegans Cbl homolog, Sli-1, was shown to act as a negative regulator of epidermal growth factor receptor signalling. This finding forced a reassessment of the role of Cbl proteins and highlighted the desirability of testing genetically whether c-Cbl acts as a negative regulator of mammalian signalling. Here we investigate the role of c-Cbl in development and homeostasis in mice by targeted disruption of the c-Cbl locus. c-Cbl-deficient mice were viable, fertile, and outwardly normal in appearance. Bone development and remodelling also appeared normal in c-Cbl mutants, despite a previously reported requirement for c-Cbl in osteoclast function. However, consistent with a high level of expression of c-Cbl in the hemopoietic compartment, c-Cbl-deficient mice displayed marked changes in their hemopoietic profiles, including altered T-cell receptor expression, lymphoid hyperplasia, and primary splenic extramedullary hemopoiesis. The mammary fat pads of mutant female mice also showed increased ductal density and branching compared to those of their wild-type littermates, indicating an unanticipated role for c-Cbl in regulating mammary growth. Collectively, the hyperplastic histological changes seen in c-Cbl mutant mice are indicative of a normal role for c-Cbl in negatively regulating signalling events that control cell growth. Consistent with this view, we observed greatly increased intracellular protein tyrosine phosphorylation in thymocytes following CD3epsilon cross-linking. In particular, phosphorylation of ZAP-70 kinase in thymocytes was uncoupled from a requirement for CD4-mediated Lck activation. This study provides the first biochemical characterization of any organism that is deficient in a member of this unique protein family. Our findings demonstrate critical roles for c-Cbl in hemopoiesis and in controlling cellular proliferation and signalling by the Syk/ZAP-70 family of protein kinases.

Animals↗