Biomedical subjects

David Little

Publications and source records attributed to David Little.

10 recordsLinked to original sources

PubMed2006

Effect of zoledronic acid in an L6-L7 rabbit spine fusion model.

Previous studies have shown that zoledronic acid administration can increase mineral content and strength in distraction osteogenesis. Of the few studies that have examined the use of bisphosphonates in spinal arthrodesis, none have assessed the effect of single dose treatment. The objective of this study was to evaluate the feasibility of enhancing spinal fusion rate using single dose zoledronic acid (ZA) to increase fusion-mass size and mineral density. Forty-eight New Zealand white rabbits underwent an L6-L7 intertransverse process fusion. The L6-L7 model is more challenging than the more commonly used level of L5-L6. Animals were randomly allocated to one of three groups, one received iliac crest bone graft alone, one group received iliac crest bone graft with locally administered zoledronic acid, 20 microg, and one group received iliac crest bone graft with a single dose of systemically administered zoledronic acid, 0.1 mg/kg. ZA doses were administered at the time of surgery. Twenty-four rabbits were culled at 6 weeks and 24 rabbits were culled at 12 weeks. Success of spinal fusion was determined by manual palpation. Specimens were evaluated radiographically, underwent quantitative computerised tomography analysis and were tested biomechanically in flexion and extension. In the six-week group, only five of the 24 spines fused with no noticeable trend with respect to treatment. In the 12-week group there was a trend toward increased fusion in the systemically administered ZA group (63%) versus the other two groups (25%) but was not statistically significant (p = 0.15). Radiographically, the local ZA treatment group showed a delay in remodelling with the presence of unremodelled bone chips. The 12-week systemic ZA group exhibited an 86% increase in BMC, a 31% increase in vBMD and a 41% increase in the volume of the fusion-mass (p < 0.05). The 12-week local ZA group also showed significant increases in BMC (69%), vBMD (31%) and total fusion-mass volume (29%) (p < 0.05). Biomechanical testing showed that the range of motion in flexion decreased to 4.5 (+/-2.5) degrees and 4.8 (+/-4.7) degrees for the local and systemic groups respectively compared to 9.6 (+/-4.9) degrees for the control group (p < 0.05). This study has shown that zoledronic acid increased fusion-mass size and bone mineral content. Systemic ZA led to an increased fusion rate; however the fusion rate remained below 100%. We suggest that bisphosphonate treatment may require an anabolic conjunctive therapy to ensure enhanced successful fusion.

Animals↗

PubMed2006

High-throughput quantification for a drug mixture in rat plasma-a comparison of Ultra Performance liquid chromatography/tandem mass spectrometry with high-performance liquid chromatography/tandem mass spectrometry.

A quantitative Ultra Performance liquid chromatography/tandem mass spectrometry (UPL/MS/MS) protocol was developed for a five-compound mixture in rat plasma. A similar high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) quantification protocol was developed for comparison purposes. Among the five test compounds, three preferred positive electrospray ionization (ESI) and two preferred negative ESI. As a result, both UPLC/MS/MS and HPLC/MS/MS analyses were performed by having the mass spectrometer collecting ESI multiple reaction monitoring (MRM) data in both positive and negative ion modes during a single injection. Peak widths for most standards were 4.8 s for the HPLC analysis and 2.4 s for the UPLC analysis. There were 17 to 20 data points obtained for each of the LC peaks. Compared with the HPLC/MS/MS method, the UPLC/MS/MS method offered 3-fold decrease in retention time, up to 10-fold increase in detected peak height, with 2-fold decrease in peak width. Limits of quantification (LOQs) for both HPLC and UPLC methods were evaluated. For UPLC/MS/MS analysis, a linear range up to four orders of magnitude was obtained with r2 values ranging from 0.991 to 0.998. The LOQs for the five analytes ranged from 0.08 to 9.85 ng/mL. Three levels of quality control (QC) samples were analyzed. For the UPLC/MS/MS protocol, the percent relative standard deviation (RSD%) for low QC (2 ng/mL) ranged from 3.42 to 8.67% (N = 18). The carryover of the UPLC/MS/MS protocol was negligible and the robustness of the UPLC/MS/MS system was evaluated with up to 963 QC injections.

Animals↗

PubMed2005

Biocide dosing remains difficult.

Despite the sums above and large amounts of research on various biocides being available, the actual choice and effectiveness of biocides is still very variable. It is still not possible to predict why a part cular biocide may work in some situations and not in others. Cost-effective biocide dosing in the field remains a "black art". It is important to check that the biocide programme is appropriate for the particular cooling system. It is essential that the reasons for using a particular programme are documented (notes will possibly be sufficient). If the programme is ineffective, then investigations into why it is not working are made so that any remedial action is taken rapidly. If the remedial action taken s not effective, further options can be tried. The monitoring of biocides and bacterial control is an extremely important aspect of an effective water treatment programme.

Anti-Bacterial Agents↗

PubMed2004

Integrated high capacity solid phase extraction-MS/MS system for pharmaceutical profiling in drug discovery.

A method is described for use in analysis of samples from pharmaceutical profiling of early drug discovery compounds. The method consists of a high capacity autosampler which injects samples into one of two solid phase extraction columns operated in parallel for alternating trapping, washing and elution into a tandem quadrupole mass spectrometer operated in multiple reaction monitoring (MRM) MS/MS mode. A primary method, which is useful for 80-90% of compounds, and a secondary method, which is useful for a majority of the remaining compounds, are described. No analytical HPLC column is used and the analysis rate is approximately 50 samples/h. Specificity is obtained using MRM analysis. Application of the method for high capacity analysis of metabolic stability samples is described.

Drug Design↗

PubMed2004

Applications of a travelling wave-based radio-frequency-only stacked ring ion guide.

The use of radio-frequency (RF)-only ion guides for efficient transport of ions through regions of a mass spectrometer where the background gas pressure is relatively high is widespread in present instrumentation. Whilst multiple collisions between ions and the background gas can be beneficial, for example in inducing fragmentation and/or decreasing the spread in ion energies, the resultant reduction of ion axial velocity can be detrimental in modes of operation where a rapidly changing influx of ions to the gas-filled ion guide needs to be reproduced at the exit. In general, the RF-only ion guides presently in use are based on multipole rod sets. Here we report investigations into a new mode of ion propulsion within an RF ion guide based on a stack of ring electrodes. Ion propulsion is produced by superimposing a voltage pulse on the confining RF of an electrode and then moving the pulse to an adjacent electrode and so on along the guide to provide a travelling voltage wave on which the ions can surf. Through appropriate choice of the travelling wave pulse height, velocity and gas pressure it will be shown that the stacked ring ion guide with the travelling wave is effective as a collision cell in a tandem mass spectrometer where fast mass scanning or switching is required, as an ion mobility separator at pressures around 0.2 mbar, as an ion delivery device for enhancement of duty cycle on an orthogonal acceleration time-of-flight (oa-TOF) mass analyser, and as an ion fragmentation device at higher wave velocities.

Computer-Aided Design↗

PubMed2004

Short-term safety assessment in the use of intravenous zoledronic acid in children.

The clinical side effects of the potent new bisphosphonate zoledronic acid in children are unknown. In this study of 34 children with various bone disorders, the frequency of postinfusion flu-like illness, hypocalcemia, and hypophosphatemia was 85%, 74%, and 82%, respectively. No renal side effects were detected after up to 3 consecutive infusions.

Adolescent↗

PubMed2004

A locally created EBM course for faculty development.

International EBM workshops have significant barriers and lack focus on institutional needs. The authors describe a local EBM curriculum and report its effectiveness and participant satisfaction. Local EBM experts devised an EBM course designed to improve faculty understanding of EBM skills and concepts. Retention of EBM concepts was assessed with a 10-item EBM knowledge test administered before and after the course. Participants were also asked to self-assess five EBM skills immediately after and nine months after the course. They also filled out a satisfaction survey. In total, 61% of the participants completed the course. The EBM knowledge test showed a significant change in scores for EBM concepts. The participants' self-assessed EBM skills remained high at nine months. Participants rated most course variables highly. It is concluded that a locally developed EBM faculty curriculum can succeed if scholars define institutional needs, receive broad institutional support, use proven educational methodologies and avoid scheduling conflicts.

Curriculum↗

PubMed2004

Pelvic fractures and associated injuries in children.

BACKGROUND: Pelvic fractures occur uncommonly in children. Despite serious sequelae, they have been infrequently reviewed. METHODS: We conducted a retrospective review of admissions to our institution from January 1983 to December 2000. RESULTS: One hundred twenty children with pelvic fractures were identified. Median age was 9 years (range, 1-16 years) and 66% (n = 80) were boys. Pedestrian-motor vehicle injury accounted for 68% (n = 82) of cases. Associated injuries were present in 78% (n = 94). Management of the pelvic fracture was nonoperative in 113 (94%). Thirty-two children (27%) required surgery for associated injuries. Complications during admission occurred in 28% (n = 34). Five children died as a result of their injuries. With a mean follow-up of 36 months (range, 7-156 months), 27% (n = 32) of children suffered an adverse outcome, including neurologic dysfunction and leg-length discrepancies. CONCLUSION: The majority of pelvic fractures in children may be satisfactorily treated nonoperatively. Operative interventions were more frequently required for associated injuries. Long-term review is indicated because of delayed complications in children that are continuing to grow and develop.

Adolescent↗

PubMed2004

Comprehensive computerised primary care records are an essential component of any national health information strategy: report from an international consensus conference.

In many countries, primary care informatics has developed to the point that it is recognised as an important enabler of quality improvement; this has not occurred to date in the United States. With this conference, we aimed to build an international consensus as to whether primary care has unique characteristics that require an informatics subspecialty; and, if so, to establish the role of primary care informatics in improving patient care, and to enable its recognition in the national strategy.The conference was organised by the primary care informatics working groups of AMIA, EFMI, IMIA and Wonca and took place at Medinfo 2004 in San Francisco. It consisted of two plenary lectures, two small-group work sessions and a panel discussion to summarise the day. It was attended by an international audience of 53 health informaticians, mostly working in primary care. There was consensus among the participants that primary care has many unique characteristics that justify the existence of an informatics subspecialty: primary care informatics (PCI). The conference identified principles and practical examples of: (1) the effective deployment of information technology to underpin the provision of records, communication and access to information; (2) the need to harness the extensive knowledge base about the practice of PCI; and (3) the contribution of the experimental work and theory that underpins the science of PCI. These principles and examples of their practical application were largely derived from the extensive knowledge base which has been built up in countries that have developed PCI over the last one to two decades.

Health Policy↗

PubMed2002

Liquid chromatography/electrospray tandem mass spectrometric analysis of incurred ractopamine residues in livestock tissues.

Ractopamine HCl is a beta-adrenergic agonist (beta-agonist) recently approved by the U.S. Food and Drug Administration, but not other governmental agencies, for use in finishing swine. For these reasons, it was important to develop and validate mass spectrometric methods for the detection and confirmation of ractopamine residues in livestock marker tissues. Incurred tissues in cattle, sheep, turkeys, and ducks were generated during 7-day ractopamine feeding (20 ppm in diets) periods. Disposition of ractopamine residues in liver and pigmented retinal epithelium was determined in animals slaughtered with withdrawal periods of 0, 3, and 7 days. Ractopamine residues, purified using solid-phase extraction, were measured using liquid chromatography (LC) and electrospray with detection by tandem mass spectrometry (MS/MS) in the multiple reaction-monitoring (MRM) mode. Total ractopamine residues (parent ractopamine + hydrolyzed conjugates) in liver were detected in all species on withdrawal day 0 (2-97 ppb) and were greatly diminished in all species by withdrawal day 7 (<1 ppb). Bovine and ovine retina had lower levels of ractopamine (0.5-3 ppb) than liver, and occular residues increased with withdrawal time, suggesting redistribution into this tissue. Lower limits of quantification were found to be approximately 0.1 ppb in liver and retina. Incurred ractopamine residues were confirmed by the precise and accurate agreement of MRM intensity ratios of diagnostic fragment ions (m/z 284, 164, and 121) from the protonated molecule between ractopamine residues in incurred samples and an authentic ractopamine standard. The limits of confirmation in liver and retina using recognized acceptance criteria were below 1 ppb. The high sensitivity and specificity for measurement and confirmation of ractopamine residues suggests this method will be applicable for regulatory residue surveillance programs.

Animals↗