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Biomedical subjects

A McClelland

Publications and source records attributed to A McClelland.

At least 19 recordsLinked to original sources
PubMed2003

Trend to better nutrition on Australian hospital menus 1986-2001 and the impact of cook-chill food service systems.

OBJECTIVE: To assess trends in the nutritional quality of hospital menus and examine differences between menus used in hospitals with cook-chill or cook-fresh food services. DESIGN: Standard patient menus were analysed against 28 criteria to assess nutritional standards and compared with results from similar studies in 1986 and 1993. SETTING: Menus were collected from 80 hospitals in New South Wales (NSW), Australia, including 36 using cook-chill food service systems. STATISTICAL ANALYSIS: Chi-squared analysis was used to assess differences between the proportions of hospitals meeting the criteria in 1993 and 2001, and between different types of hospitals. RESULTS: In 2001, compared with 1993, significantly many hospitals offered more than one hot choice at the evening meal, more menus highlighted low fat items and more calcium-rich foods were available. More than 90% of hospitals allowed patients to select their own menu, offered wholemeal breads and high-fibre breakfast cereals, fresh fruit, polyunsaturated margarine, a milk dessert at least once a day and two or more hot options at the midday meal. Hospitals with cook-chill food services had menus that were more likely to meet nutritional recommendations, although they were less likely to offer a choice of serving size. A high proportion of unpopular choices were offered in menus, especially meat dishes and desserts. APPLICATIONS/CONCLUSION: Since 1986, NSW hospital menus have improved to offer choices that conform better to dietary guidelines. Cook-chill food services may have positive and negative impacts on meal choices. The assessment criteria are useful in hospitals to assess their menus.

Australia↗
PubMed2002

Development and implementation of computerized clinical guidelines: barriers and solutions.

Research indicates that computerized decision support systems (CDSSs) can improve clinical performance and patient outcomes, and yet CDSSs are not in widespread use. Physician guidelines, in general, face barriers in implementation. Guidelines in a computerized format can overcome some of the barriers to conventional text-form guidelines; however, computerized programs have novel aspects that have to be considered, aspects such as technical problems/support and user interface issues that can act as barriers. Though the literature points out that human, organizational, and technical issues can act as barriers in the implementation of CDSSs, studies clearly indicate that there are methods that can overcome these barriers and improve CDSS acceptance and use. These methods come from lessons learned from a variety of CDSS implementation ventures. Notably, most of the methods that improve acceptance and use of a CDSS require feedback and involvement of end-users. Measuring and addressing physician or user attitudes toward the computerized support system has been shown to be important in the successful implementation of a CDSS. This article discusses: 1) the barriers of implementation of guidelines in general and of CDSSs; 2) the importance of the physician's role in development, implementation, and adherence; 3) methods that can improve CDSS acceptance and use; and 4) the types of tools needed to obtain end-user feedback.

Attitude of Health Personnel↗
PubMed2001

Agreement between troponin T levels from plain and heparinized tubes.

OBJECTIVE: To determine whether there was a clinically significant effect on troponin T measurement when the sample was collected in a heparinized (plasma) blood collection tube compared with a serum tube. METHODS: Prospective cohort study using a convenience sample of 198 patients with undifferentiated illness presenting to an Emergency Department who required troponin T measurement. Samples were collected in both plain (serum) tubes and plasma tubes for comparison. All samples were measured using an Elecsys 2010 Immunoassay system (Roche-Boehringer Mannheim, Germany). RESULTS: There were 35 troponin T measurements > or = 0.03 microg/L (the limit of reproducibility of the test). The negative predictive value for troponin T performed in heparinized tubes compared with plain tubes was 100% (95% confidence interval 96.4-100) at the > or = 0.03 microg/L level and 100% (95% confidence interval 97-100%) at the > or = 0.1 microg/L level. At a cut-off point for risk stratification in acute coronary syndromes (> or = 0.1 microg/L), there was 100% concordance between the two measurements for each sample. CONCLUSION: The use of plasma (heparinized) tubes for the collection of troponin T samples is unlikely to produce clinically significant false-negative results compared with collection of troponin T samples in serum (plain) tubes.

Blood Specimen Collection↗
PubMed2000

Evidence for gene transfer and expression of factor IX in haemophilia B patients treated with an AAV vector.

Pre-clinical studies in mice and haemophilic dogs have shown that introduction of an adeno-associated viral (AAV) vector encoding blood coagulation factor IX (FIX) into skeletal muscle results in sustained expression of F.IX at levels sufficient to correct the haemophilic phenotype. On the basis of these data and additional pre-clinical studies demonstrating an absence of vector-related toxicity, we initiated a clinical study of intramuscular injection of an AAV vector expressing human F.IX in adults with severe haemophilia B. The study has a dose-escalation design, and all patients have now been enrolled in the initial dose cohort (2 x 10(11) vg/kg). Assessment in the first three patients of safety and gene transfer and expression show no evidence of germline transmission of vector sequences or formation of inhibitory antibodies against F.IX. We found that the vector sequences are present in muscle by PCR and Southern-blot analyses of muscle biopsies and we demonstrated expression of F.IX by immunohistochemistry. We observed modest changes in clinical endpoints including circulating levels of F.IX and frequency of FIX protein infusion. The evidence of gene expression at low doses of vector suggests that dose calculations based on animal data may have overestimated the amount of vector required to achieve therapeutic levels in humans, and that the approach offers the possibility of converting severe haemophilia B to a milder form of the disease.

Adult↗
PubMed2000

Decisions concerning the allocation of scarce medical resources.

This paper aimed to determine the criteria participants use to make decisions about scarce medical resources (allocation to use a kidney machine). It varied information about patients on 4 factors (sex, smoking, employment status, community service). It also set out to see if decisions made in groups differed from aggregated decisions of those made alone. In the first study, participants completed a simple questionnaire requiring them to rank-order sixteen hypothetical patients. In the second study, a group discussion (in groups of three participants) preceded the group putting an agreed rating on the identical questionnaire. Participants favoured patients who were employed, non-smokers and participated in community service. This suggests that participants adopted a utilitarian moral ideology. Participants' smoking habits interacted with the hypothetical patients' smoking habits, indicating in-group favouritism. In the second study it was found that when the decision was made in a group of three it amplifies the decision made by an individual. In this sense there was clear evidence of group polarization.

Choice Behavior↗
PubMed1999

Expression of tissue inhibitor of matrix metalloproteinases 1 by use of an adenoviral vector inhibits smooth muscle cell migration and reduces neointimal hyperplasia in the rat model of vascular balloon injury.

BACKGROUND: Cell migration is a major contributor to injury-induced neointimal hyperplasia and depends on alteration of the proteolytic balance within the arterial wall toward matrix breakdown. This is partly mediated by the matrix metalloproteinases (MMPs) and their natural inhibitors, the tissue inhibitors of metalloproteinases (TIMPs). METHODS AND RESULTS: An increase in expression of biologically active and immunoreactive TIMP-1 was seen in vitro after infection of rat smooth muscle cells (SMCs) with Av1.TIMP1 (an adenoviral vector containing the human TIMP1 cDNA). Infection of rat SMCs with Av1.TIMP1 reduced migration in vitro by 27% compared with control virus-infected cells (37.6+/-4.34 versus 51+/-5.01 cells per high-power field, P<0.05). The adenoviral vector was delivered to the injured rat carotid artery, and 4 days later, immunoreactive protein was identified and migration of SMCs reduced by 60% (5.2+/-0. 5 versus 12.8+/-1.5 cells per section, P<0.05, n=5). Neointimal area 14 days after injury showed a 30% reduction in the animals receiving the Av1.TIMP1 virus compared with controls (0.09+/-0.01 versus 0. 14+/-0.01 mm2, P=0.02, n=14). CONCLUSIONS: The response to arterial balloon injury involves MMP-dependent SMC migration and can be attenuated in vivo by the transmural expression of TIMP-1 by adenoviral gene transfer.

Adenoviridae↗
PubMed1999

Enhanced neuroblastoma transduction for an improved antitumor vaccine.

BACKGROUND: A recent clinical trial of an antineuroblastoma vaccine used adenovirus serotype 5 (Ad5) vectors to transduce autologous tumor cells with the gene encoding IL-2. A method to improve transduction efficiency was sought to enable the use of lower viral titers, especially when in situ adenoviral-mediated tumor cell transduction is considered. MATERIALS AND METHODS: A chimeric adenoviral delivery vector was utilized in which the fiber head from adenovirus serotype 3 was incorporated into the backbone of Ad5. Since the fiber head protein is responsible for viral attachment to target cells, a different spectrum and range of infectivity might result. Both the chimeric (Av9LacZ4) and Ad5 (Av1LacZ4) vectors were constructed to carry a beta-galactosidase transgene. The relative transduction efficiency of these two vectors was then evaluated in five tumor-derived short-term neuroblastoma cultures and four established neuroblastoma cell lines. Enzyme activity was assessed using three different methods: in situ staining, flow cytometric analysis, and a quantitative assay. RESULTS: A significant improvement in transduction efficiency of the short-term neuroblastoma cultures with the new chimeric adenovector was demonstrated. A similar improvement in transduction efficiency was not observed in the established cell lines, suggesting that the cell surface receptor for the Ad 3 serotype had been lost in vitro. Increased transduction of tumor cells with N-myc amplification was also observed. CONCLUSIONS: The newly constructed chimeric adenoviral vector transduces short-term neuroblastoma cultures more efficiently than the standard Ad5 vector. This vector will permit the use of lower viral titers and may be useful in other adenoviral-based gene-therapy protocols. Increased transgene expression in N-myc-amplified cells offers possible selectivity for in situ gene delivery.

Adenoviruses, Human↗
PubMed1999

Adenovirus-mediated expresssion of the murine ecotropic receptor facilitates transduction of human hematopoietic cells with an ecotropic retroviral vector.

One factor limiting the ability to modify human repopulating hematopoietic cells genetically with retroviral vectors is the relatively low expression of the cognate viral receptor. We have tested sequential transduction of human hematopoietic cells with an adenoviral vector encoding the ecotropic retroviral receptor followed by transduction with an ecotropic retroviral vector. Adenoviral transduction of K562 erythroleukemia cells was highly efficiently with >95% of cells expressing the ecotropic receptor at a multiplicity of infection (MOI) of 103with a correspondingly high transduction with a retroviral vector. Ecotropic receptor expression in CD34+ cells following transduction with adenoviral vectors was increased by at least two-fold (from 20 to 48%) by replacing the RSV promoter with the CMV E1a promoter, resulting in a parallel increase in retroviral transduction efficiency. Replacing the head portion of the fiber protein in conventional adenoviral vectors (serotype 5) with the corresponding portion from an adenoviral 3 serotype resulted in ecotropic receptor expression in 60% of CD34+ cells at an MOI of 104 and a retroviral transduction of 60% of hematopoietic clonogenic progenitors. The sequential transduction strategy also resulted in efficient transduction of the primitive CD34+CD38- subset suggesting that it may hold promise for genetic modification of human hematopoietic stem cells.

Adenoviridae↗
PubMed1998

Evidence for a grammar-specific deficit in children.

BACKGROUND: Specific language impairment (SLI) is a disorder in which language acquisition is impaired in an otherwise normally developing child. SLI affects around 7% of children. The existence of a purely grammatical form of SLI has become extremely controversial because it points to the existence and innateness of a putative grammatical subsystem in the brain. Some researchers dispute the existence of a purely grammatical form of SLI. They hypothesise that SLI in children is caused by deficits in auditory and/or general cognitive processing, or social factors. There are also claims that the cognitive abilities of people with SLI have not yet been sufficiently characterised to substantiate the existence of SLI in a pure grammatical form. RESULTS: We present a case study of a boy, known as AZ, with SLI. To investigate the claim for a primary grammatical impairment, we distinguish between grammatical abilities, non-grammatical language abilities and non-verbal cognitive abilities. We investigated AZ's abilities in each of these areas. AZ performed normally on auditory and cognitive tasks, yet exhibited severe grammatical impairments. This is evidence for a developmental grammatical deficit that cannot be explained as a by-product of retardation or auditory difficulties. CONCLUSIONS: The case of AZ provides evidence supporting the existence of a genetically determined, specialised mechanism that is necessary for the normal development of human language.

Adolescent↗
PubMed1998

Sustained phenotypic correction of murine hemophilia A by in vivo gene therapy.

Hemophilia A is caused by a deficiency of blood coagulation factor VIII (FVIII) and has been widely discussed as a candidate for gene therapy. While the natural canine model of hemophilia A has been valuable for the development of FVIII pharmaceutical products, the use of hemophiliac dogs for gene therapy studies has several limitations such as expense and the long canine generation time. The recent creation of two strains of FVIII-deficient mice provides the first small animal model of hemophilia A. Treatment of hemophiliac mice of both genotypes with potent, human FVIII-encoding adenoviral vectors resulted in expression of biologically active human FVIII at levels, which declined, but remained above the human therapeutic range for over 9 months. The duration of expression and FVIII plasma levels achieved were similar in both hemophiliac mouse strains. Treated mice readily survived tail clipping with minimal blood loss, thus showing phenotypic correction of murine hemophilia A by in vivo gene therapy.

Adenoviridae↗
PubMed1998

Circumvention of immunity to the adenovirus major coat protein hexon.

Immunity to adenoviruses is an important hurdle to be overcome for successful gene therapy. The presence of antibodies to the capsid proteins prevents efficacious adenovirus vector administration in vivo. We tested whether immunity to a particular serotype of adenovirus (Ad5) may be overcome with a vector that encodes the hexon sequences from a different adenovirus serotype (Ad12). We successfully constructed an adenovirus vector with a chimeric Ad5-Ad12 hexon which was not neutralized by plasma from C57BL/6 mice immunized with Ad5. The vector was also capable of transducing the livers of C57BL/6 mice previously immunized with Ad5.

Adenoviruses, Human↗
PubMed1998

Factors affecting nonmedical participants' allocation of scarce medical resources.

This study was designed to determine the factors that affect nonmedical participants' judgments in constructing a ranked waiting list for kidney patients requiring dialysis. Participants (N=167) were given a questionnaire that provided minimal demographic data about 16 hypothetical patients. Participants were requested to rank patients in order of priority for treatment. Each participant's personal demographic details were also obtained. Patients differed on four dimensions: gender, income, alcohol consumption, and religious beliefs, yielding a 2x2x2x2 design. The participants favoured for treatment included females over males, "poor" over "rich," nondrinkers over drinkers, and Christians over atheists. Results are discussed in terms of establishing democratic criteria and informing medical personnel on explicit factors which may affect their decision making, thus guarding against biases in judgment.

Age Factors↗
PubMed1997

Expression of human cholesterol 7alpha-hydroxylase in atherosclerosis-susceptible mice via adenovirus infection.

Adenovirus is a vector for the delivery of genes mainly to the liver. Short-term (approximately 3 days) studies using adenovirus transfection have provided valuable insights into how genes can complement normal and pathological phenotypes. When atherosclerosis-susceptible C57BL/6 mice were infected with an adenovirus vector containing the human 7alpha-hydroxylate cDNA (AV17h1) and fed on a chow diet, human 7alpha-hydroxylase mRNA and enzyme activity doubled compared with that in mice infected with an adenovirus vector (AV1Null) alone. In AV17h1-infected mice fed on a high fat cholic acid (HFCA) diet, mRNA expression and activity of both the endogenous and adenovirus (human) 7alpha-hydroxylase were repressed. AV17h1-infected mice fed on a HFCA diet and killed at mid-light had increased 7alpha-hydroxylase activity and mRNA compared with mice killed at mid-dark. Since expression of AV17h1 is driven by a constitutive Rous sarcoma virus promoter, the repression of human 7alpha-hydroxylase by the HFCA diet was unexpected. In spite of this post-transcriptional repression by the HFCA diet, AV17h1-infected mice expressed the human 7alpha-hydroxylase mRNA, causing its enzyme activity to be 3-fold greater than in AV1Null-infected mice. In AV17h1-infected mice, the 7alpha-hydroxylase enzyme activity varied as a linear function of human mRNA abundance. In conclusion, the accumulation of apolipoprotein B-containing lipoproteins in plasma of C57BL/6 mice fed on the HFCA diet was not reduced by longer-term (2 weeks) 7alpha-hydroxylase expression, probably because of its diminished expression caused by the diet and hepatic inflammation from the adenovirus infection. These results may suggest that adenovirus is effective in promoting longer-term (2 weeks) expression of 7alpha-hydroxylase.

Adenoviridae Infections↗
PubMed1997

Surface expression of intercellular adhesion molecule 1 on epithelial cells in the human adenoid.

Human rhinoviruses enter the host by way of the nose and conjunctiva. Intercellular adhesion molecule 1 (ICAM-1) is the cellular receptor for the majority of rhinoviruses. ICAM-1 expression on the luminal surface of epithelial cells in the upper airway may be an important determinant of virus localization in the airway. Eighteen adenoids and 5 nasopharyngeal biopsies were evaluated by immunohistochemistry for surface expression of ICAM-1. Heavy immunoreactivity of ICAM-1 was found on the surface of a small number of single nonciliated cells in the lymphoepithelium. Squamous epithelial cells showed minimal to no staining, and ciliated epithelium had positive ICAM-1 staining of the basal cells but not on the ciliated border. The localization of ICAM-1 expression to specific, limited areas of the surface epithelium of the nasopharynx may have important implications in the pathogenesis of rhinovirus infections, especially initiation of the host response to rhinovirus.

Adenoids↗
PubMed1997

Selective targeting of human cells by a chimeric adenovirus vector containing a modified fiber protein.

The adenovirus fiber protein is responsible for attachment of the virion to unidentified cell surface receptors. There are at least two distinct adenovirus fiber receptors which interact with the group B (Ad3) and group C (Ad5) adenoviruses. We have previously shown by using expressed adenovirus fiber proteins that it is possible to change the specificity of the fiber protein by exchanging the head domain with another serotype which recognizes a different receptor (S. C. Stevenson et al., J. Virol. 69:2850-2857, 1995). A chimeric fiber cDNA containing the Ad3 fiber head domain fused to the Ad5 fiber tail and shaft was incorporated into the genome of an adenovirus vector with E1 and E3 deleted encoding beta-galactosidase to generate Av9LacZ4, an adenovirus particle which contains a chimeric fiber protein. Western blot analysis of the chimeric fiber vector confirmed expression of the chimeric fiber protein and its association with the adenovirus capsid. Transduction experiments with fiber protein competitors demonstrated the altered receptor tropism of the chimeric fiber vector compared to that of the parental Av1LacZ4 vector. Transduction of a panel of human cell lines with the chimeric and parental vectors provided evidence for a different cellular distribution of the Ad5 and Ad3 receptors. Three cell lines (THP-1, MRC-5, and FaDu) were more efficiently transduced by the vector containing the Ad3 fiber head than by the Ad5 fiber vector. In contrast, human coronary artery endothelial cells were transduced more readily with the vector containing the Ad5 fiber than with the chimeric fiber vector. HeLa and human umbilical vein endothelial cells were transduced at equivalent levels compared with human diploid fibroblasts, which were refractory to transduction with both vectors. These results provide evidence for the differential expression of the Ad5 and Ad3 receptors on human cell lines derived from clinically relevant target tissues. Furthermore, we show that exchange of the fiber head domain is a viable approach to the production of adenovirus vectors with cell-type-selective transduction properties. It may be possible to extend this approach to the use of ligands for a range of different cellular receptors in order to target gene transfer to specific cell types at the level of transduction.

Adenoviridae↗