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Biomedical subjects

D Booth

Publications and source records attributed to D Booth.

At least 19 recordsLinked to original sources
PubMed2006

Point-of-care testing of neonatal coagulation.

The aim of this validation study was to compare prothrombin time (PT) and activated partial thromboplastin time (APTT) results from a point-of-care testing (POCT) device (Rapidpoint Coag) with those from standard laboratory tests. The subjects were newborn infants needing coagulation screen for any clinical indications within a regional neonatal intensive care unit. The level of agreement between POCT and laboratory measurements of PT and APTT was determined. For PT: the bias was from -7.6 to 12.4 s and precision was 5.0 s. For the detection of prolonged PT at a level of 16 s, the sensitivity was 0.70, specificity was 0.57 and the positive predictive value (PPV) was 0.62. For APTT: the bias was from -39.1 to 23.7 s, and precision was 15.7 s. For the detection of prolonged APTT at a level of 55 s, the sensitivity was 0.80, specificity was 0.95 and the PPV was 0.80. The POCT device tested has limited utility as a cot-side device for screening for a prolongation of the APTT in the newborn but is not sensitive for screening for prolongation of the PT.

Female↗
PubMed2004

Anticonvulsants for neonates with seizures.

BACKGROUND: Neonatal seizures are a common problem and most neonates with seizures are treated with anticonvulsants. There is wide variation in clinical practice in both diagnosis and treatment of such seizures and this reflects the lack of clear evidence of the relative benefit and harm of the anticonvulsants used. The routine use of anticonvulsants to treat seizures in neonates needs to be evaluated. OBJECTIVES: To assess and compare (with respect to benefits and harm) different anticonvulsants administered to neonates for the treatment of established seizures. SEARCH STRATEGY: Relevant randomised controlled trials were identified using a combination of electronic database searches (MEDLINE 1966 - March 2004, EMBASE 1980 - March 2004), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2004) and hand searches. Identification of ongoing or unpublished trials was attempted by contacting prominent authors in the field and searching electronic registers of ongoing trials. SELECTION CRITERIA: All randomised or quasi-randomised controlled clinical trials with reported data comparing the following outcomes: mortality, neurodevelopmental disability, need for additional anticonvulsants, need for maintenance anticonvulsants at discharge and adverse events (hypotension requiring volume or inotropic support, arrhythmia, respiratory depression, hepatotoxicity) in neonates treated for seizures with systemic anticonvulsants compared to placebo, no drug or alternative anticonvulsants. DATA COLLECTION AND ANALYSIS: Methodological quality and validity were assessed without consideration of the results. The first reviewer screened the title and abstracts of studies identified by the above search strategy. Full text versions of studies of potential relevance were re-screened by both reviewers. Studies meeting the pre-specified inclusion criteria were included. Relevant data were extracted and analysed separately and any disagreements were resolved by discussion. MAIN RESULTS: Only two randomised controlled trials published in full could be identified. Painter 1999 showed that both of the two most commonly used anticonvulsants (phenobarbital and phenytoin) were similarly effective (RR 1.03 95% CI 0.96 to 1.62), controlling seizures in less than fifty percent of infants. Painter 1999 did not report mortality or neurodevelopmental outcome. Boylan 2004 randomised infants who failed to respond to phenobarbital to receive either lidocaine or midazolam as second-line agents. There was a trend for lidocaine to be more effective in reducing seizure burden (RR 0.40 95% CI 0.14 to 1.17) but both groups had similarly poor long term outcomes assessed at one year. REVIEWERS' CONCLUSIONS: At present there is little evidence from randomised controlled trials to support the use of any of the anticonvulsants currently used in the neonatal period. In the literature, there remains a body of opinion that seizures should be treated because of the concern that seizures in themselves may be harmful, although this is only supported by relatively low grade evidence (Levene 2002; Massingale 1993). Development of safe and effective treatment strategies relies on future studies of high quality (randomised controlled trials with methodology that assures validity) and of sufficient size to have the power to detect clinically important reductions in mortality and severe neurodevelopmental disability in addition to any short term reduction in seizure burden.

Anticonvulsants↗
PubMed2004

Teduglutide ([Gly2]GLP-2) protects small intestinal stem cells from radiation damage.

Glucagon-like peptide-2 and its dipeptidyl peptidase (DP-IV) resistant analogue teduglutide are trophic for the gastrointestinal epithelium. Exposure increases villus height and crypt size and results in increased overall intestinal weight. As these effects may be mediated through stimulation of the stem cell compartment, they may promote intestinal healing and act as potential anti-mucositis agents in patients undergoing cancer chemotherapy. A study was initiated to investigate the protective effects of teduglutide on the murine small intestinal epithelium following gamma-irradiation using the crypt microcolony assay as a measure of stem cell survival and functional competence. Teduglutide demonstrated intestinotrophic effects in both CD1 and BDF1 mouse strains. In BDF1 mice, subcutaneous injection of GLP-2 or teduglutide (0.2 mg/kg/day, b.i.d.) for 14 days increased intestinal weight by 28% and resulted in comparable increases in crypt size, villus height and area. Teduglutide given daily for 6 or 14 days prior to whole body, gamma-irradiation significantly increased crypt stem cell survival when compared with vehicle-treated controls. The mean levels of protection over a range of doses provided protection factors from 1.3 to 1.5. A protective effect was only observed when teduglutide was given before irradiation. These results suggest that teduglutide has the ability to modulate clonogenic stem cell survival in the small intestine and this may have a useful clinical application in the prevention of cancer therapy-induced mucositis.

Animals↗
PubMed2003

A genome-wide screen for linkage disequilibrium in Australian HLA-DRB1*1501 positive multiple sclerosis patients.

The association of multiple sclerosis with alleles/haplotypes from the HLA region on chromosome 6p21 is well established although the remainder of the genome remains relatively unexplored. We have completed a genome-wide screen for linkage disequilibrium in a cohort of Australian multiple sclerosis patients positive for HLA-DRB1*1501. A total of 4346 microsatellite markers provided through the "Genetic Analysis of Multiple sclerosis in EuropeanS" (GAMES) collaborative were analysed in DNA separately pooled from cases (n=217) and controls (n=187). Associations were found in four genomic regions (12q15, 16p13, 18p11 and 19q13) previously identified in linkage genome screens. Three additional regions of novel association were also identified (11q12, 11q23 and 14q21). Further analysis of these regions is required to establish whether the associations observed are due to epistatic interaction with the HLA locus.

Adult↗
PubMed2002

Cell kinetic studies in the murine ventral tongue epithelium: thymidine metabolism studies and circadian rhythm determination.

The oral mucosa is a rapidly replacing body tissue that has received relatively little attention in terms of defining its cell kinetics and cellular organization. The tissue is sensitive to the effects of cytotoxic agents, the consequence of which can be stem cell death with the subsequent development of ulcers and the symptoms of oral mucositis. There is considerable interest in designing strategies to protect oral stem cells and, hence, reduce the mucositis side-effects in cancer therapy patients. Here we present details of a new histometric approach designed to investigate the changing patterns in cellularity in the ventral tongue mucosa. This initial paper in a series of four papers presents observations on the changing patterns in the labelling index following tritiated thymidine administration, which suggest a delayed uptake of tritiated thymidine from a long-term intracellular thymidine pool, a phenomenon that will complicate cell kinetic interpretations in a variety of experimental situations. We also provide data on the changing pattern of mitotic activity through a 24-h period (circadian rhythms). Using vincristine-induced stathmokinesis, the data indicate that 54% of the basal cells divide each day and that there is a high degree of synchrony in mitotic activity with a mitotic peak occurring around 13.00 h. The mitotic circadian peak occurs 9-12 h after the circadian peak in DNA synthesis. The data presented here and in the subsequent papers could be interpreted to indicate that basal cells of BDF1 mice have an average turnover time of about 26-44 h with some cells cycling once a day and others with a 2- or 3-day cell cycle time.

Animals↗
PubMed2002

Cell kinetic studies in murine ventral tongue epithelium: cell cycle progression studies using double labelling techniques.

The dorsal and ventral epithelia on the murine tongue exhibit very pronounced circadian rhythms in terms of the cell cycle. These rhythms are such that three injections of tritiated thymidine 3 h apart spanning the circadian peak in S phase cells labelled between 40 and 50% of the basal cells. Injection of bromodeoxyuridine generally gave slightly lower labelling indices. Approximately the same proportion (54% of the basal cells) could be accumulated in metaphase over a 24-h period using vincristine as a stathmokinetic agent. The experiments reported here using mouse ventral tongue epithelium use double-labelling approaches to address the question: what proportion of the approximately 50% of the basal cells that are proliferating have a 24-h cell cycle and can therefore be labelled by a similar labelling protocol the following day? The results suggest a heterogeneity amongst the proliferating basal cells, similar to the heterogeneity proposed for the dorsal tongue epithelium. Although not all the basal component has been accounted for, the data presented here suggest that about 20% of the basal cells may have a cell cycle time of 24 h, about 30% appear to have a longer cell cycle time (48 or 72 h), while about 20% of the basal cells appear to be postmitotic maturing G1 cells, awaiting the appropriate signals for migration into the suprabasal layer.

Animals↗
PubMed2002

Cell kinetic studies in the murine ventral tongue epithelium: the effects of repeated exposure to keratinocyte growth factor.

Keratinocyte growth factor (KGF) stimulates proliferation and differentiation in various epithelial systems. Three daily subcutaneous injections of 125 microg of this protein into mice induce dramatic changes in the histology and histometric measurements of the ventral tongue epithelium. The thickness of the epithelium is increased two-fold and the number of cells beneath a 1-mm length of the surface is increased 1.6-fold. KGF also induces a four-fold increase in the number of S phase cells labelled with tritiated thymidine in the basal layer on the third day after KGF administration. The increase in thickness and cellularity persist for at least 4 days after the end of the KGF injections. However, there is a dramatic fall in the number of S phase cells detected by 3HTdR pulse labelling 2 days after the end of the KGF treatment. There are indications that by 7 days after the 3-day regimen of KGF treatment, both thickness and cellularity have fallen back to near control levels. Continued exposure to KGF over a period of 7 days does not result in any further increases in thickness, cellularity or proliferation. In fact, the proliferation decreases on the fifth, sixth and seventh days of KGF injection to control values on day 7. These changes in the epithelium following KGF treatment suggest that the thicker and more cellular epithelium may be more able to cope with an exposure to a cytotoxic agent and hence be protected in comparison with normal or vehicle-treated epithelium.

Animals↗
PubMed2002

Cell kinetic studies in the murine ventral tongue epithelium: mucositis induced by radiation and its protection by pretreatment with keratinocyte growth factor (KGF).

Radiation kills or reduces reproductive capacity of proliferating cells, including stem cells. In the oral mucosae this can result in a decline in the number of cells in the tissue which, if severe enough, will result in the formation of an ulcer when the cellularity essentially reaches zero. We have used histometric measurements of cellularity following exposure to radiation in mouse ventral tongue epithelium as a model for oral mucositis (ulcer development). Here we provide further measurements of cellularity changes in the basal layer and in the epithelium as a whole at various times following 15, 20 or 25 Gy doses. The protective effects of prior treatment with keratinocyte growth factor (KGF) are also investigated. 20 Gy of 300 kV X-rays has become our standard reference dose and the changes in cellularity seen following this dose are highly reproducible, with minimum values being observed 6 days following irradiation. A higher dose results in a greater reduction of cellularity, although the minimum value also occurs at 6 days. A lower dose (15 Gy) results in a much shallower curve, with a minimum value being observed about 1 day earlier. These changes in cellularity can be related to the less sensitive index of mucositis, namely epithelial thickness. There is also a sharp peak in proliferation about 1 day after the minimum in cellularity, i.e. on day 7. The peak following a lower dose of radiation occurs a little earlier and, following the higher dose, the peak tends to be broader. Previous work and data presented in the preceding paper in this series has shown that KGF, given over a period of 3 days, results in a dramatic increase in epithelial thickness in oral mucosa, including the ventral tongue. As a result of the increased cellularity induced by KGF given before radiation, a delay in the fall in cellularity results, which is the consequence of the increased number of cells in the epithelium at the beginning of the study.

Animals↗
PubMed2002

Arthritis and use of dental services: a population based study.

BACKGROUND: Rheumatoid arthritis (RA) and osteoarthritis (OA) are chronic systemic conditions that can have a profound effect on oral health as the result of physical disability, immunosuppressant and other medications and autoimmune disease. However, there is insufficient information available on the use of dental services by the people suffering from RA or OA. The purpose of this study was to investigate dental visits and factors associated with dental attendance in those with RA and OA in order to improve access to dental care in these groups. METHODS: The study used population based data from the 1995 National Health Survey (total n=53828). The main variables of interest were reported RA (n=1193) and OA (n=3091) and the main outcome variable was having visited a dental professional in the previous 12 months. Chi-square analysis was performed using SAS software. RESULTS: The proportion of people visiting a dental professional in previous 12 months was significantly less in both RA and OA respondents compared to non-arthritic respondents. Both males and females with RA and OA were found to be less likely to have visited a dental professional when compared to general population (p=0.001 in each case). Furthermore, the findings have revealed that RA and OA patients living in metropolitan centres were more likely to have a dental visit than those living in rural or remote areas (p=0.001 in each case). CONCLUSIONS: When compared to non-arthritic subjects, all patients with RA and OA were less likely to receive dental care, in particular preventive care. This is especially important in patients with Sjogren's Syndrome and those who are immunosuppressed.

Adolescent↗
PubMed2002

Willingness to pay for flood and ecological risk reduction in an urban watershed.

Urban watershed managers frequently must address alternative policy goals; flood control and ecological risk reduction. This study combines hydrologic models of flood control and biotic models of ecologic risk with economic models of willingness-to-pay and psychological models of risk processing and planned behavior to evaluate these two alternative policy objectives. The findings reveal that flood risk exposure, especially for those individuals who would remain outside the 100 year flood plain if the project were enacted, does influence the financial support that local residents would be willing to make to a flood control project. Other important determinants include demographic factors such as income, and attitudinal measures of the respondent. Expanding the scope of the project to include ecological risk reduction does not, however, appear to change the average willingness-to-pay for a project.

Demography↗
PubMed2001

Appropriate procedures for the safe handling and pathologic examination of technetium-99m-labelled specimens.

Technetium 99m may now be used to identify sentinel nodes for surgical excision in a growing number of cancer sites. The pathology specimens of these sentinel nodes and of any injected tumoural sites are radioactive. Consequently, specific clinical and laboratory procedures must be developed to handle these specimens safely. It is recommended that specimens containing the injection site should be quarantined for a period to permit decay of radioactivity. This quarantine does delay the reporting of pathology results to surgeons, oncologists and other clinicians, but it does not adversely affect final patient management.

Canada↗
PubMed2001

ENCORE: the effect of nutrient enrichment on coral reefs. Synthesis of results and conclusions.

Coral reef degradation resulting from nutrient enrichment of coastal waters is of increasing global concern. Although effects of nutrients on coral reef organisms have been demonstrated in the laboratory, there is little direct evidence of nutrient effects on coral reef biota in situ. The ENCORE experiment investigated responses of coral reef organisms and processes to controlled additions of dissolved inorganic nitrogen (N) and/or phosphorus (P) on an offshore reef (One Tree Island) at the southern end of the Great Barrier Reef, Australia. A multi-disciplinary team assessed a variety of factors focusing on nutrient dynamics and biotic responses. A controlled and replicated experiment was conducted over two years using twelve small patch reefs ponded at low tide by a coral rim. Treatments included three control reefs (no nutrient addition) and three + N reefs (NH4Cl added), three + P reefs (KH2PO4 added), and three + N + P reefs. Nutrients were added as pulses at each low tide (ca twice per day) by remotely operated units. There were two phases of nutrient additions. During the initial, low-loading phase of the experiment nutrient pulses (mean dose = 11.5 microM NH4+; 2.3 microM PO4(-3)) rapidly declined, reaching near-background levels (mean = 0.9 microM NH4+; 0.5 microM PO4(-3)) within 2-3 h. A variety of biotic processes, assessed over a year during this initial nutrient loading phase, were not significantly affected, with the exception of coral reproduction, which was affected in all nutrient treatments. In Acropora longicyathus and A. aspera, fewer successfully developed embryos were formed, and in A. longicyathus fertilization rates and lipid levels decreased. In the second, high-loading, phase of ENCORE an increased nutrient dosage (mean dose = 36.2 microM NH4+; 5.1 microM PO4(-3)) declining to means of 11.3 microM NH4+ and 2.4 microM PO4(-3) at the end of low tide) was used for a further year, and a variety of significant biotic responses occurred. Encrusting algae incorporated virtually none of the added nutrients. Organisms containing endosymbiotic zooxanthellae (corals and giant clams) assimilated dissolved nutrients rapidly and were responsive to added nutrients. Coral mortality, not detected during the initial low-loading phase, became evident with increased nutrient dosage, particularly in Pocillopora damicornis. Nitrogen additions stunted coral growth, and phosphorus additions had a variable effect. Coral calcification rate and linear extension increased in the presence of added phosphorus but skeletal density was reduced, making corals more susceptible to breakage. Settlement of all coral larvae was reduced in nitrogen treatments, yet settlement of larvae from brooded species was enhanced in phosphorus treatments. Recruitment of stomatopods, benthic crustaceans living in coral rubble, was reduced in nitrogen and nitrogen plus phosphorus treatments. Grazing rates and reproductive effort of various fish species were not affected by the nutrient treatments. Microbial nitrogen transformations in sediments were responsive to nutrient loading with nitrogen fixation significantly increased in phosphorus treatments and denitrification increased in all treatments to which nitrogen had been added. Rates of bioerosion and grazing showed no significant effects of added nutrients. ENCORE has shown that reef organisms and processes investigated in situ were impacted by elevated nutrients. Impacts were dependent on dose level, whether nitrogen and/or phosphorus were elevated and were often species-specific. The impacts were generally sub-lethal and subtle and the treated reefs at the end of the experiment were visually similar to control reefs. Rapid nutrient uptake indicates that nutrient concentrations alone are not adequate to assess nutrient condition of reefs. Sensitive and quantifiable biological indicators need to be developed for coral reef ecosystems. The potential bioindicators identified in ENCORE should be tested in future research on coral reef/nutrient interactions. Synergistic and cumulative effects of elevated nutrients and other environmental parameters, comparative studies of intact vs. disturbed reefs, offshore vs. inshore reefs, or the ability of a nutrient-stressed reef to respond to natural disturbances require elucidation. An expanded understanding of coral reef responses to anthropogenic impacts is necessary, particularly regarding the subtle, sub-lethal effects detected in the ENCORE studies.

Animals↗
PubMed2001

Percutaneous coronary intervention versus coronary artery bypass graft surgery for patients with medically refractory myocardial ischemia and risk factors for adverse outcomes with bypass: a multicenter, randomized trial. Investigators of the Department of Veterans Affairs Cooperative Study #385, the Angina With Extremely Serious Operative Mortality Evaluation (AWESOME).

BACKGROUND: Percutaneous coronary intervention (PCI) and coronary artery bypass graft surgery (CABG) are being applied to high-risk populations, but previous randomized trials comparing revascularization methods have excluded a number of important high-risk groups. OBJECTIVES: This five-year, multicenter, randomized clinical trial was designed to compare long-term survival among patients with medically refractory myocardial ischemia and a high risk of adverse outcomes assigned to either a CABG or a PCI strategy, which could include stents. METHODS: Patients from 16 Veterans Affairs Medical Centers were screened to identify myocardial ischemia refractory to medical management and the presence of one or more risk factors for adverse outcome with CABG, including prior open-heart surgery, age >70 years, left ventricular ejection fraction <0.35, myocardial infarction within seven days or intraaortic balloon pump required. Clinically eligible patients (n = 2,431) underwent coronary angiography; 781 were angiographically acceptable; 454 (58% of eligible) patients consented to random assignment between CABG and PCI. RESULTS: A total of 232 patients was randomized to CABG and 222 to PCI. The 30-day survivals for CABG and PCI were 95% and 97%, respectively. Survival rates for CABG and PCI were 90% versus 94% at six months and 79% versus 80% at 36 months (log-rank test, p = 0.46). CONCLUSIONS: Percutaneous coronary intervention is an alternative to CABG for patients with medically refractory myocardial ischemia and a high risk of adverse outcomes with CABG.

Aged↗
PubMed2001

Protection against mucosal injury by growth factors and cytokines.

This article provides an overview of published studies in which growth factors and cytokines were used to modify the sensitivity of intestinal stem cells to a dose of radiation. In these experiments, growth factors were used to manipulate the sensitivity of stem cells in the gastrointestinal tract to reduce the severity of gastrointestinal mucositis in cancer therapy patients. Transforming growth factor beta3, interleukin 11, and keratinocyte growth factor were used. All three agents, given according to appropriate protocols, can result in a threefold to fourfold increase in the number of intestinal stem cells that survive a dose of radiation therapy. This result was assessed by using the crypt microcolony assay of stem cell functional capacity. The changes in stem cell survival that were observed resulted in increased animal survival. This increased survival was taken as a surrogate for improvement in patient well-being. The severity of diarrhea, a marker of functional impairment, was concomitantly reduced.

Animals↗
PubMed2001

Risk based urban watershed management under conflicting objectives.

Ecological impairment and flooding caused by urbanization can be expressed numerically by calculating the risks throughout the watershed (floodplain) and along the main stems of the streams. The risks can be evaluated in terms of the present and/or future. This article describes the methodologies for ascertaining the risks in the Geographical Information Systems (GIS) environment. The objectives of urban flood controls and ecological preservation/restoration of urban waters are often conflicting and, in the past, the sole emphasis on flood control led to destruction of habitat and deterioration of water quality. An optimal solution to these two problems may be achieved by linking the risks to the concepts of risk communication, risk perception, and public willingness to pay for projects leading to ecological restoration and ecologically sustainable flood control. This method is appropriate because, in each case, public funds are used and the projects require approval and backing of policy makers and stakeholders. This article briefly describes a research project that attempts to resolve the conflict between the flood protection and stream ecological preservation and restoration and suggests alternative ways of expressing benefits of urban stream flood control and restoration projects.

Cities↗