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Biomedical subjects

David J Wright

Publications and source records attributed to David J Wright.

30 records · Page 2Linked to original sources
PubMed2003

Increasing blood availability by changing donation patterns.

BACKGROUND: There is a declining margin between US blood collections and transfusions. Donation patterns were examined to characterize returning first-time donors and predict the impact on blood availability of decreasing the number of nonreturning donors. STUDY DESIGN AND METHODS: First-time donors giving between 1991 and 1994 were followed for 3 to 6 years. The impact of decreasing the number of nonreturning donors in a 12-month period was projected using the Poisson distribution to model the donation patterns of 539,063 donors who gave in 1995. Repeat donors were classified as "returning first-time" (gave a first-time donation within 12 months of their index donation), "established" (gave a repeat donation), and "inactive" (didn't donate in the 12 months before their index donation). RESULTS: A total of 49 percent of first-time donors did not return within 6 years. Returning first-time donors tended to be US born, white, and had more than a high school education. In 1995, 30 percent of donors were first time, 31 percent were established, 7 percent were returning first time, and 32 percent were inactive, giving 1.5, 2.4, 1.9, and 1.7 donations in 12 months, respectively. Reducing nonreturning donors by 5 percent could increase blood collections by 2.7 percent. Similarly, 15 or 25 percent reductions in nonreturns could increase collections by 8.6 or 16.0 percent, respectively. CONCLUSIONS: Most donors are not giving near the donation limit. A substantial increase in donations could be achieved by a relatively small decrease in donor nonreturn. Research is needed to understand why approximately half of first-time donors donate only once.

Behavior↗
PubMed2003

Comparative sensitivity of HBV NATs and HBsAg assays for detection of acute HBV infection.

BACKGROUND: A study was designed to estimate relative analytic sensitivity and window-period (WP) closure and to project incremental yield of newer HBsAg tests, pooled-sample NAT, and single-sample NAT, compared to currently licensed HBsAg tests. STUDY DESIGN AND METHODS: HBV DNA and HBsAg test results for 23 HBV seroconversion (SC) panels were first analyzed to construct a model of primary HBV viremia. One-hundred representative samples were then selected from 10 panels and coded with 28 analytical controls. All 128 samples were tested by seven HBsAg tests and by four pooled-sample and three single-sample NAT assay formats. Results were analyzed to obtain differential times to HBV detection and combined with HBV incidence rates to project comparative yields. RESULTS: HBV doubling time during the ramp-up phase was estimated at 2.56 days. HBsAg concentrations at cutoff for new tests ranged from 0.07 to 0.12 ng per mL, compared with 0.13 to 0.62 ng per mL for licensed tests. Estimated viral load at cutoff ranged from 102 to 267 IU per mL for new tests and from 363 to 1069 IU per mL for licensed tests. HBsAg tests detected 31 to 63 percent of early ramp-up phase samples in the 100-member seroconversion panel study, while pooled-sample NAT detected 55 to 71 percent and single-sample NAT, 82 to 99 percent. Compared with currently licensed HBsAg assays, newer HBsAg assays would reduce the WP by 2 to 9 days; pooled-sample NAT would reduce the WP by 9 to 11 days; and single-sample NAT would reduce the WP by 25 to 36 days. CONCLUSION: Newer HBsAg tests would be expected to detect an additional 15 to 21 infected units per 107 donations, compared to licensed HBsAg tests. Sensitivity, WP closure, and yield projections for newer HBsAg assays and pooled-sample NAT are comparable. Single-sample NAT would increase yield by 13 to 15 units per 107 donations over pooled-sample NAT and newer HBsAg assays and by 35 to 50 units per 107 donations over currently licensed HBsAg assays.

Acute Disease↗
PubMed2003

DNA sequencing using rolling circle amplification and precision glass syringes in a high-throughput liquid handling system.

An automated high-throughput method that employs rolling circle amplification (RCA) to generate template for large-scale DNA sequencing has been developed using liquid handling systems equipped with precision glass syringes. A protocol was designed to perform the sequencing analysis from template preparation to thermal cycle sequencing within the same vessel, thus minimizing the amount of liquid handling and transfer. The amplified DNA was directly used for cycle sequencing with no need for any purification procedures. Total RCA reaction volumes as low as 500 nL generated sufficient templates for successful sequencing. Reducing the RCA total reaction volumes by a 40-fold factor, from a total of 20 microL to 500 nL, resulted in a significant reduction in cost, from $1.25/reaction to less than $0.04/reaction. Additionally, the volume of the sequencing reactions was reduced from a total of 20 to 10 microL, thus generating a further cost advantage. This high-throughput DNA sequencing protocol maximizes the speed and precision of processing while significantly reducing the cost of amplification.

Algorithms↗
PubMed2002

DNA topoisomerase II is essential for preimplantation mouse development.

Topoisomerase II (topo II) is an essential enzyme that alters DNA topology. This activity is important for a variety of chromosome functions including DNA replication, transcription, recombination, and chromosome condensation and segregation. Previously we localized topo II in mouse gametes and preimplantation embryos using isoform-specific antibodies demonstrating the presence of the enzyme in oocytes and embryos, but not sperm. To probe functions of topo II during preimplantation development, we treated mouse zygotes with 100 nM teniposide, and assessed embryo morphology and DNA replication. Teniposide blocked cleavage in 69% embryos; the remainder cleaved once but had abnormal nuclei. Teniposide-treated embryos were devoid of topo II immunofluorescence. Teniposide also prevented DNA replication, implicating topo II in this process. Embryos treated with a 2 hr pulse of teniposide recovered and developed to the blastocyst stage, indicating 100 nM teniposide did not induce apoptosis. To more specifically analyze topo IIalpha function, we treated zygotes with topo IIalpha-targeted antisense oligodeoxynucleotides. Most zygotes arrested at the 2-cell stage while controls developed into blastocysts indicating topo IIalpha is essential for preimplantation development. The absence of topo IIalpha, but not beta immunofluorescence in antisense-treated embryos confirms the specificity and impact of the treatment. In addition, topo IIalpha is newly synthesized at the 2-cell stage. These results establish an essential function for topo II in mouse preimplantation embryonic development.

Animals↗
PubMed2002

DNA topoisomerase II distribution in mouse preimplantation embryos.

DNA topoisomerase II (topo II) is an essential enzyme that mediates a variety of chromosome activities including DNA replication, transcription, recombination, and chromosome condensation and segregation. Isoform-specific anti-topo II antibodies were used to determine the distribution of topo II alpha and beta in mouse gametes and embryos. Immunoblot analysis with two anti-topo IIalpha antibodies revealed that a 170 kDa topo IIalpha band was present in ovary and testis. Mature sperm exhibited an 89 kDa band only, which may be a degradation product of topo IIalpha. Immunoblots probed with a monoclonal antibody that recognizes both isoforms, showed bands at 170 and 180 kDa, which correspond to topo IIalpha and beta, respectively. An additional 100 kDa band was also present in ovary and testis. Mature sperm did not exhibit staining with this antibody. We also localized topo II in mouse gametes and embryos up to the blastocyst stage using immunofluorescence microscopy. While both isoforms were found in nuclei and nucleoli of germinal vesicle oocytes, topo IIalpha localized to metaphase chromosomes during meiosis, and only to nucleoli during embryonic interphase. Topo IIbeta was absent from chromosomes of metaphase II oocytes, but localized to embryonic interphase nuclei. Both full-length isoforms were absent from sperm, indicating topo II is stored maternally. These results identify topo II as an important component of mouse oocyte and embryonic chromatin, and suggest its involvement in oocyte maturation and preimplantation embryonic development. The different immunofluorescent staining patterns indicate topo IIalpha and beta may serve different roles during the embryonic cell cycle.

Animals↗
PubMed2002

Pharmacoeconomic evaluation of a patient education letter aimed at reducing long-term prescribing of benzodiazepines.

OBJECTIVE: To determine the economic implications of sending an educational letter to patients, aimed at reducing long-term BDZ prescribing. METHOD: Letters were sent to 242 patients from 2 general medical practices. BDZ usage and costs were compared in the years before and after intervention using numbers of defined daily dosages (DDDs) prescribed. The cost of intervention implementation was estimated using pharmacist, GP and administrative staff time, plus postage costs. MAIN OUTCOME MEASURES: Number of BDZ DDDs prescribed during the 12-month periods before and after intervention. The cost implications of intervention. RESULTS: Mean patient age was 67 years, 75% were female and the mean duration of BDZ usage was 19 years. A mean of 337 benzodiazepine DDDs per patient were prescribed during the baseline year. Overall BDZ usage at baseline was increasing by 13%. After receiving the letter, 31% of patients discussed BDZ usage with their GP and 10% had their drug or strength changed. During the year after intervention, a significant reduction of 17% in benzodiazepine usage was observed compared to baseline; 5% of patients ordered no more benzodiazepine prescriptions after receiving the letter. Mean BDZ costs reduced by 1.20 Pounds per patient after intervention. The cost of intervention implementation was 5.54 Pounds per patient, giving a net cost of 4.34 Pounds per patient, or 86.80 Pounds to obtain one BDZ discontinuation. CONCLUSION: This intervention is effective, simple, and inexpensive. Its minimal cost could be justified given the morbidity associated with the long-term prescribing of benzodiazepines, particularly in the elderly.

Adult↗
PubMedDate not supplied

An assessment of a multiplex PCR assay for differentiating clinically important mycobacteria based on pncA gene variation.

The pncA genes in mycobacteria are responsible for the production of pyrazinamidase (PZase). In Mycobacterium tuberculosis, PZase hydrolyses pyrazinamide (PZA) to pyrazonic acid, a compound that possesses bactericidal activity against tubercle bacilli. Nucleotide sequences of pncA genes found within mycobacteria where aligned in an effort to ascertain the significance of any variability in sequence. Three sets of primers (one degenerate and five consensus sequences) were designed and employed in a multiplex PCR assay to amplify the pncA region in seven clinically common mycobacteria. The banding patterns generated from each species in conjunction with PZase activity tests demonstrated that the mycobacterial species examined could be clearly identified and differentiated from one another. Although not yet tested with clinical isolates, the combination of these two assays has provided a promising discriminatory tool for the identification of commonly encountered clinical mycobacteria species.

Amidohydrolases↗
PubMedDate not supplied

Supporting students with disabilities.

The use of workshops to inform and question practice is common. Two workshops on supporting learners with disabilities in the clinical environment are described with support from the literature. Examples of discrimination are outlined showing a wide variation in the NHS before the implementation of the Disability Discrimination Act 1995. Participants outlined barriers to learning in clinical environments and ways of overcoming those barriers. They also discussed the need to develop support mechanisms.

Attitude↗