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PubMed1986

Simplified lysed-blood culture technique.

A blood culture system was developed in which a lysing agent (either Tween 20, one of several other polyoxyethylene adducts, digitonin, or Triton X-100) is added to the blood culture medium. Of 33 Triton compounds, 9 lysed human blood, as did 7 of 21 polyoxyethylene compounds and digitonin, all at a concentration of 0.05%. Under the specific test conditions, three of the hemolytic polyoxyethylene compounds and digitonin had no inhibitory effect. All of the Triton compounds had at least some inhibitory effect on the most sensitive of the pathogenic bacteria that were tested, Streptococcus pneumoniae and Neisseria meningitidis. Because of results from previous studies, Triton X-100 was tested further, despite evidence in this study of its inhibition of bacteria. Of the 55 lysing agents tested, digitonin, Triton X-100, Brij 96, and Tween 20 were selected for further testing as additions to conventional culture broth. Comparative culture studies with bacteremic blood from infected rabbits were performed with the conventional blood culture, the Isolator system (Du Pont Co., Wilmington, Del.), and the new lysing medium. The new system has the advantages of lysis filtration and lysis centrifugation without the associated added cost and processing complexity.

Animals↗

PubMed1993

Restriction endonuclease analysis of clinical Pseudomonas aeruginosa strains: useful epidemiologic data from a simple and rapid method.

Newer genetic techniques have replaced phenotypic methods of subtyping Pseudomonas aeruginosa strains. Widespread application of newer methodologies, however, may be limited by technologic complexity and the cost of equipment. We conducted restriction endonuclease analysis (REA) of sheared genomic DNAs from 48 clinical P. aeruginosa strains using the enzyme SalI and electrophoresis in horizontal, low-concentration (0.3 to 0.6%) agarose gels. Each REA profile consisted of a smear of lower-molecular-mass bands as well as a countable number of well-resolved bands in the 8.3- to 48.5-kbp range which could easily be compared when isolates were run side-by-side on the same gel. In general, the REA patterns of strains recovered from different patients differed by at least seven bands, and those of serial isolates from individual patients were identical or differed by, at most, two bands over this 8.3- to 48.5-kbp range. REA of strains already subtyped by field inversion gel electrophoresis revealed that the two techniques generally paralleled each other. Overall, some unrelated strains had similar REA profiles, but the relative simplicity and low cost of the approach coupled with the ability to demonstrate differences between most unrelated strains should make this type of REA an attractive first step in the investigation of institutional P. aeruginosa problems.

Adult↗

PubMed1980

Improving prognosis for infants weighing 1000 g or less at birth.

In the two years 1977 and 1978, 55 infants weighing less than or equal to 1000 g were admitted to the neonatal unit of the Queen Victoria Medical Centre. Overall neonatal survival was 60%; 44% of infants weighing 501-750 g and 67% of infants weighing 751-1000 g survived. One postneonatal death occurred at 51 days. Maternal risk factors were present in 80% of infants, although none had an effect on survival. Perinatal asphyxia, as indicated by an Apgar score less than or equal to 3 at five minutes, and base deficit greater than 10 mmol/l on admission, were associated with decreased survival. Mortality data with increasing postnatal age were used to produce a chart for sequential predication of neonatal survival. Intraventricular haemorrhage remained the most common necropsy finding. Follow-up of 32 survivors to date has shown no abnormalities, with the exception of one retrolental fibroplasia, and one porencephaly of unknown aetiology. We conclude that the prognosis for infants weighing less than or equal to 1000 g has continued to improve. From a review of the clinical and pathological characteristics in these infants however, it is obvious that this outcome requires complex organisation and costly resources in perinatal centres to which high-risk pregnancies must be transferred for optimal management both before and after birth.

Australia↗

PubMed1998

Urea breath tests in the management of Helicobacter pylori infection.

The 13/14C-Urea breath test (UBT) is based on the simple principle that a solution of isotopically labelled urea will be rapidly hydrolysed by the abundantly expressed urease of H pylori. The released 13/14CO2 is absorbed across the mucus layer to the gastric mucosa and hence, via the systemic circulation, excreted in the expired breath. Distribution of urea throughout the stomach prevents sampling error and allows semiquantitative assessments of the extent of H pylori infection. Originally the 13C-UBT was complex, cumbersome and costly but, by simplifying the protocol and reducing the number of samples to be analysed, is now a much easier, quicker and cheaper test for detecting H pylori. Although mass spectrometry is needed for analysis of exhaled 13CO2, the use of the stable isotope, which is completely safe, provides advantages over the 14C-UBT using radioactive 14C-urea, such that it can be used in women and children and a user's licence is not required. The widespread availability of scintigraphy for 14CO2 analysis may make the 14C-UBT seem an attractive alternative to the 13C-UBT. However, there are no standard protocols for the 14C-UBT and although the methods are similar, several different cut off values are used which makes formal validation studies still necessary. Both tests are easy to perform with minimum opportunity for observer variation or methodological error; they are very sensitive and specific tests and provide a clinical "gold standard" against which the accuracy of other tests can be validated. The 13/14C-UBT detects only current infection and can be used to screen for H pylori infection and as the sole method for assessing eradication. In addition, because the 13C-UBT can be performed repeatedly in the same subject, it can be used to monitor the effects of novel anti-H pylori therapies and for epidemiological studies in children.

Breath Tests↗

PubMed2000

Strategy for prevention and control of the risks due to noise.

OBJECTIVES: To propose a strategy for progressively controlling the exposure to noise in industry as much as possible. To propose a method that could, in the first stage, be used by the workers and management themselves to control exposures to noise as much as possible, and then, in later stages, when necessary, progressively call in the assistance of specialists and experts to identify more complex solutions and organise personal protection and medical surveillance. METHODS: The strategy includes three stages. Stage 1 is observation, simple and easy to use by the workers to recognise the problems, identify straightforward solutions, and call for assistance when needed. Stage 2 is analysis, more complex but more costly, performed with the assistance of occupational health specialists to identify more technical control measures and set up a programme to conserve hearing. Stage 3 is expertise, performed with the assistance of acoustic experts for special measurements and control measures. CONCLUSIONS: The proposed strategy enriches the assessment procedure that is usually recommended, by providing for one preliminary stage used by the people directly concerned. It explicitly recognises (a) the competence of the workers and management about their working conditions and (b) that knowledge and measurements of acoustics are not an absolute prerequisite for solving-at least partly-noise problems. It attempts to organise in sequence and optimise the cooperation between the workers, the occupational health specialists, and the experts in acoustics.

Acoustics↗

PubMedDate not supplied

Fluoroscopy: recording of fluoroscopic images and automatic exposure control.

Some means of recording images is a necessary part of most fluoroscopic systems. Several methods are available for recording images during fluoroscopy. Screen-film recording methods such as use of spot film devices and automatic film changers provide high-spatial-resolution images. Recording images by using the image intensifier (fluorography) provides film or digital images at relatively lower doses but with poorer spatial resolution. Digitally recorded images have better contrast resolution than analog images but lower spatial resolution and represent a compromise between dose and image quality. Motion picture (cine fluorographic) recording requires extremely high dose rates compared with those of lower-resolution videotape recording of motion. Recording systems in fluoroscopy require automatic exposure control for optimum image quality. The same feedback system used to control fluorographic exposures can be used to control exposure rates during fluoroscopy as well. Automatic brightness control maintains intensifier exposure rates on the basis of subject thickness by adjusting various technique factors. The type of control mechanism depends on the imaging task and the complexity (age and cost) of the equipment. The operator can choose between better image quality (higher contrast) or lower radiation dose.

Fluoroscopy↗

PubMed2003

Quantitative assessment of the importance of dye switching and biological replication in cDNA microarray studies.

Dye switching and biological replication substantially increase the cost and the complexity of cDNA microarray studies. The objective of the present analysis was to quantitatively assess the importance of these procedures to provide a quantitative basis for decision-making in the design of microarray experiments. Taking advantage of the unique characteristics of a published data set, the impact of these procedures on the reliability of microarray results was calculated. Adding a second microarray with dye switching substantially increased the correlation coefficient between observed and predicted ln(ratio) values from 0.38 +/- 0.06 to 0.62 +/- 0.04 (n = 12) and the outlier concordance from 21 +/- 3% to 43 +/- 4%. It also increased the correlation with the entire set of microarrays from 0.60 +/- 0.04 to 0.79 +/- 0.04 and the outlier concordance from 31 +/- 6% to 58 +/- 5% and tended to improve the correlation with Northern blot results. Adding a second microarray to include biological replication also improved the performance of these indices but often to a lesser degree. Inclusion of both procedures in the second microarray substantially improved the consistency with the entire set of microarrays but had minimal effect on the consistency with predicted results. Analysis of another data set generated using a different cDNA labeling method also supported a significant impact of dye switching. In conclusion, both dye switching and biological replication substantially increased the reliability of microarray results, with dye switching likely having even greater benefits. Recommendations regarding the use of these procedures were proposed.

Algorithms↗

PubMed2001

Liquid ventilation: from experimental use to clinical application.

Despite advances in perinatal care of preterm infants, complications of prematurity are still common. If new conventional ventilatory interventions fail, ECMO is the only alternative method, but is a complex, invasive and costly technique and difficult to apply to small infants. Perfluorocarbon liquid ventilation is a promising technique. It has been demonstrated to be effective in experimental models, in mature and immature animals. However, its role in the management of human neonates, infants, older children and adults with acute respiratory failure is still not established. Both liquid ventilation strategies, total and partial, are able not only to maintain gas exchange, but also to reduce inflammatory changes. While total liquid ventilation remains as an experimental technique, partial liquid ventilation could be readily applied, but its implementation in clinical practice awaits results from ongoing and future clinical trials that may define its effectiveness.

Fluorocarbons↗

PubMed2001

Nutrition and prostate cancer.

Nutrition is apparently a major risk factor for the development and progression of prostate cancer. Based on experimental studies and epidemiologic data mainly from case-control studies or cohort studies, there is strong evidence that reduction of the total energy consumption, a diet comprising less than 30% fat, and increased intake of phytoestrogens, vitamins D and E and selenium could yield a decreased prostate cancer incidence. Furthermore, some of these measures appear to have antitumoral capacity even in the presence of the disease. These observations have provided a rationale to forward large prospective trials on dietary interventions to prove the efficacy of the concept and further delineate the correlation between nutritional compounds and prostate cancer risk. These chemoprevention trials are either aiming a reduction prostate cancer incidence or a decrease in tumor progression. Depending on the study design, large numbers of individuals need to be enrolled and long follow-up intervals are required thus making such trials highly complex and cost-intensive. However, regarding the potential relevance of chemoprevention on public health, further efforts to identify nutritional factors affecting prostate cancer growth are warranted.

Carotenoids↗

PubMedDate not supplied

Number of potential patients to be treated with proton therapy in Italy.

In radiotherapy, the use of proton beams is one of the most promising approaches in order to reduce the treatment volume and, consequently, increase the total dose avoiding severe complications to the normal tissues surrounding the target. Among the new hospital-based facilities that are planned for the next future, the italian project is in an advanced stage of study. Because of the complexity and high cost of the italian centre, one of the most important information in order to establish the cost/benefit balance, is represented by the number of potential patients to be treated for the various pathologies. For this reason it is useful to define a priority scale of clinical indications and, on this basis, to estimate the yearly patient afflux to the center, taking into account the incidence and the expected new cases to be treated with protons. Indications have been divided into two categories, according to decreasing priority. Category A includes all the tumors in which the use of proton therapy has clearly demonstrated to be advantageous, being the only way to give a curative dose to the target. In Italy, the estimated number of this category of patients is 825 each year. Category B comprises a great variety of tumors characterized mainly by a local evolution, with a limited likelihood of distant spread, and therefore potentially cured if the local control can be obtained. The total number of potential patients in this category is more than 10,000.

Humans↗

PubMed2001

Non-invasive cardiac output determination: comparison of a new partial-rebreathing technique with thermodilution.

This study compares a derivative Fick technique using carbon dioxide (CO2) with the thermodilution pulmonary artery catheter (PAC), for determination of cardiac output (CO). Subjects were sedated, mechanically ventilated adults following elective cardiac surgery Microprocessor controlled deadspace activation and side-stream capnography in a ventilator circuit enabled calculation of CO (CO(CO2)) every four minutes. Thermodilution CO (CO(TD)) was performed as clinically indicated and at 20-minute intervals. Simultaneous CO(TD)/CO(CO2) pairs were recorded from time of admission to ICU for a minimum period of two hours for each patient. There were 358 CO(TD)/CO(CO2) pairs recorded from 41 patients. Cardiac output measurements ranged from 2. 7 to 10.6 l/min. The bias (Bland-Altman) was 0.050 l/min (95% CI -0.024 to 0.125 l/min). The 95% limits of agreement were -1.354 to 1.455 l/min. This simple, non-invasive partial-rebreathing technique is a valid alternative to thermodilution for cardiac output determination in sedated, mechanically ventilated patients. There are significant implications for improved safety, reduced complexity and reduced cost in anaesthesia and intensive care.

Adult↗

PubMed2000

Pattern recognition analysis of endogenous cell metabolites for high throughput mode of action identification: removing the postscreening dilemma associated with whole-organism high throughput screening.

Although whole-organism HTS can give clear indications of in vivo activity, typically few clues are given as to the mechanism of action (MOA), and determining the MOA for large numbers of active compounds can be costly and complex-an alternative approach is required. This report demonstrates that it is possible to conduct relatively high throughput MOA characterization of HTS hits utilizing a single sample preparation and analytical method. By monitoring a wide range of endogenous cellular metabolites via (1)H nuclear magnetic resonance spectroscopy, the MOA of herbicides can be predicted using computational methods to compare the metabolite perturbation patterns. Herbicides that induce a characteristic pattern of metabolic perturbation in maize include inhibitors of acetolactate synthase, acetyl co-enzyme A carboxylase, protoporphyrinogen oxidase, 5-enolpyruvylshikimate-3-phosphate synthase, and phytoene desaturase. In soya, photosystem II inhibitors can also be detected, further demonstrating that this method is not limited to inhibitors of enzymes that directly act upon endogenous metabolites, or a single species. The methods, including data analysis, can be readily automated, enabling relatively high throughput MOA elucidation of whole-organism screen hits. Additionally, for compounds with a novel MOA, this approach may lead to MOA identification faster than traditional methods. It is envisaged that application of these data analysis methods to other data types-for example, transcription (mRNA) or translation (protein) profiles-is likely to permit higher throughput with smaller sample requirements, along with ability to discriminate MOAs that are not adequately discriminated based upon endogenous metabolite profiles.

Automation↗

PubMed2006

Development of a macrophage-based nanoparticle platform for antiretroviral drug delivery.

Complex dosing regimens, costs, side effects, biodistribution limitations, and variable drug pharmacokinetic patterns have affected the long-term efficacy of antiretroviral medicines. To address these problems, a nanoparticle indinavir (NP-IDV) formulation packaged into carrier bone marrow-derived macrophages (BMMs) was developed. Drug distribution and disease outcomes were assessed in immune-competent and human immunodeficiency virus type 1 (HIV-1)-infected humanized immune-deficient mice, respectively. In the former, NP-IDV formulation contained within BMMs was adoptively transferred. After a single administration, single-photon emission computed tomography, histology, and reverse-phase-high-performance liquid chromatography (RP-HPLC) demonstrated robust lung, liver, and spleen BMMs and drug distribution. Tissue and sera IDV levels were greater than or equal to 50 microM for 2 weeks. NP-IDV-BMMs administered to HIV-1-challenged humanized mice revealed reduced numbers of virus-infected cells in plasma, lymph nodes, spleen, liver, and lung, as well as, CD4(+) T-cell protection. We conclude that a single dose of NP-IDV, using BMMs as a carrier, is effective and warrants consideration for human testing.

Animals↗

PubMed2005

The McKenzie Method for the management of acute non-specific low back pain: design of a randomised controlled trial [ACTRN012605000032651].

BACKGROUND: Low back pain (LBP) is a major health problem. Effective treatment of acute LBP is important because it prevents patients from developing chronic LBP, the stage of LBP that requires costly and more complex treatment. Physiotherapists commonly use a system of diagnosis and exercise prescription called the McKenzie Method to manage patients with LBP. However, there is insufficient evidence to support the use of the McKenzie Method for these patients. We have designed a randomised controlled trial to evaluate whether the addition of the McKenzie Method to general practitioner care results in better outcomes than general practitioner care alone for patients with acute LBP. METHODS/DESIGN: This paper describes the protocol for a trial examining the effects of the McKenzie Method in the treatment of acute non-specific LBP. One hundred and forty eight participants who present to general medical practitioners with a new episode of acute non-specific LBP will be randomised to receive general practitioner care or general practitioner care plus a program of care based on the McKenzie Method. The primary outcomes are average pain during week 1, pain at week 1 and 3 and global perceived effect at week 3. DISCUSSION: This trial will provide the first rigorous test of the effectiveness of the McKenzie Method for acute non-specific LBP.

Acute Disease↗

PubMed2006

What interventions should pharmacists employ to impact health practitioners' prescribing practices?

OBJECTIVE: To determine which interventions are effective in influencing health practitioners' prescribing practices and explore differences in intervention complexity, setting, sustainability, cost effectiveness, and impact on patient outcomes. METHODS: A systematic search for English-language systematic reviews was performed in MEDLINE, Cumulative Index of Nursing and Allied Health Literature, EMBASE, and the Cochrane Library from the date of inception to July 2005 using search terms in accordance with Cochrane recommendations. Included reviews were required to clearly report a search strategy, inclusion/exclusion criteria, literature assessment criteria, and methods for synthesizing or summarizing information and references. Two reviewers independently identified studies for inclusion, assessed study quality, and extracted relevant information. Interventions were classified as consistently effective, inconsistently effective, and effectiveness uncertain. RESULTS: Thirty-four of 4585 titles reviewed met the inclusion criteria. Quality scores ranged from 70% to 100%. Consistently effective interventions included reminders (manual and computerized), audit and feedback, educational outreach visits, organizational strategies, and patient-mediated interventions. Inconsistently effective interventions included computer decision support systems and educational meetings. Multi-faceted interventions were consistently shown to be more efficacious than single interventions. Limited data precluded exploration of the effects of interventions in different settings, sustainability of effect, cost effectiveness, and patient clinical outcomes. CONCLUSIONS: Interventions that are most effective for impacting prescribing practice include audit and feedback, reminders, educational outreach visits, and patient-mediated interventions. To maximize impact, pharmacists' efforts to positively impact prescribing practices should focus on these intervention types rather than relying primarily on passive didactics or dissemination of guidelines.

Drug Prescriptions↗

PubMed2004

Energy-scavenging amplifiers for miniature solid-state lasers.

Longitudinally pumped miniature lasers are inefficient, partly because of their inefficient absorption of the pump light. Scavenging the unabsorbed pump light to pump an in-line amplifier can greatly enhance the efficiency of the system, with minimal added cost, size, or complexity.

Journal Article↗

PubMed2005

A microchip CD4 counting method for HIV monitoring in resource-poor settings.

BACKGROUND: More than 35 million people in developing countries are living with HIV infection. An enormous global effort is now underway to bring antiretroviral treatment to at least 3 million of those infected. While drug prices have dropped considerably, the cost and technical complexity of laboratory tests essential for the management of HIV disease, such as CD4 cell counts, remain prohibitive. New, simple, and affordable methods for measuring CD4 cells that can be implemented in resource-scarce settings are urgently needed. METHODS AND FINDINGS: Here we describe the development of a prototype for a simple, rapid, and affordable method for counting CD4 lymphocytes. Microliter volumes of blood without further sample preparation are stained with fluorescent antibodies, captured on a membrane within a miniaturized flow cell and imaged through microscope optics with the type of charge-coupled device developed for digital camera technology. An associated computer algorithm converts the raw digital image into absolute CD4 counts and CD4 percentages in real time. The accuracy of this prototype system was validated through testing in the United States and Botswana, and showed close agreement with standard flow cytometry (r = 0.95) over a range of absolute CD4 counts, and the ability to discriminate clinically relevant CD4 count thresholds with high sensitivity and specificity. CONCLUSION: Advances in the adaptation of new technologies to biomedical detection systems, such as the one described here, promise to make complex diagnostics for HIV and other infectious diseases a practical global reality.

Algorithms↗

PubMed1975

Laboratory and clinical evaluation of a new volume ventilator.

A three phase laboratory and clinical evaluation of a new fluidically controlled volume ventilator (Ohio 550) was undertaken to determine if this more compact, less complex and less costly unit retained the multiple advantages which have been established for volume ventilators in the continuous ventilatory support of patients in respiratory failure. Inspired volume, peak pressure, and flow rates were continuously monitored while a "test lung" was ventilated with its "effective compliance" reduced, and ambulatory patients with varying degrees of obstructive and restrictive ventilatory impairment were ventilated with the 550 respirator. Since adequate tidal and minute volumes were achieved under these conditions of markedly altered breathing mechanics, ten patients in acute respiratory failure requiring mechanical ventilation were managed with the 550 respirator. Aside from the absence of a sighing device, not considered by the authors to be a major disadvantage, the mechanical characteristics, inspired oxygen control and alarm systems were judged satisfactory and compared favorably with the volume ventilators currently available. The fluidic control system is expected to enhance the reliability and minimize the maintenance required of this respirator.

Acute Disease↗