Development of a low-level 39Ar calibration standard - Analysis by absolute gas counting measurements augmented with simulation.

This paper describes the generation of 39Ar, via reactor irradiation of potassium carbonate, followed by quantitative analysis (length-compensated proportional counting) to yield two calibration standards that are respectively 50 and 3 times atmospheric background levels. Measurements were performed in Pacific Northwest National Laboratory's shallow underground counting laboratory studying the effect of gas density on beta-transport; these results are compared with simulation. The total expanded uncertainty of the specific activity for the ~50× 39Ar in P10 standard is 3.6% (k=2).

Bacteria in a water-damaged building: associations of actinomycetes and non-tuberculous mycobacteria with respiratory health in occupants.

We examined microbial correlates of health outcomes in building occupants with a sarcoidosis cluster and excess asthma. We offered employees a questionnaire and pulmonary function testing and collected floor dust and liquid/sludge from drain tubing traps of heat pumps that were analyzed for various microbial agents. Forty-nine percent of participants reported any symptom reflecting possible granulomatous disease (shortness of breath on exertion, flu-like achiness, or fever and chills) weekly in the last 4 weeks. In multivariate regressions, thermophilic actinomycetes (median = 529 CFU/m2 ) in dust were associated with FEV1 /FVC [coefficient = -2.8 per interquartile range change, P = 0.02], percent predicted FEF25-75% (coefficient = -12.9, P = 0.01), and any granulomatous disease-like symptom [odds ratio (OR) = 3.1, 95% confidence interval (CI) = 1.45-6.73]. Mycobacteria (median = 658 CFU/m2 ) were positively associated with asthma symptoms (OR = 1.5, 95% CI = 0.97-2.43). Composite score (median = 11.5) of total bacteria from heat pumps was negatively associated with asthma (0.8, 0.71-1.00) and positively associated with FEV1 /FVC (coefficient = 0.44, P = 0.095). Endotoxin (median score = 12.0) was negatively associated with two or more granulomatous disease-like symptoms (OR = 0.8, 95% CI = 0.67-0.98) and asthma (0.8, 0.67-0.96). Fungi or (1→3)-ß-D-glucan in dust or heat pump traps was not associated with any health outcomes. Thermophilic actinomycetes and non-tuberculous mycobacteria may have played a role in the occupants' respiratory outcomes in this water-damaged building.

Quality assurance in cardiovascular CT: a practical guide.

Cardiovascular computed tomography (CCT) is a cutting-edge imaging technique providing important, non-invasive, diagnostic information. Concerns exist regarding radiation exposure to patient populations, but achieving optimal image quality at the lowest doses can be challenging. This guide provides practical advice about how quality can be assured in any CCT unit or radiology department. Illustrated by real-world vignettes and data analysis from our own experience, we highlight a multidisciplinary team approach to each stage of the patient journey, the effectiveness of regular dose audit overseen by a CT optimisation group, and the importance of underused systolic scanning techniques, in order to drive significant dose reduction without loss of image quality or clinical confidence.

Myocardial Tissue Characterization: Histological and Pathophysiological Correlation.

Cardiovascular magnetic resonance imaging (CMR) has become the gold standard not only for cardiac volume and function quantification, but for a key unique strength: non-invasive myocardial tissue characterization. Several different techniques, separately or in combination, can detect and quantify early and established myocardial pathological processes permitting better diagnosis, prognostication and tracking of therapy. The authors will focus on the histological and pathophysiological evidence of these imaging parameters in the characterization of edema, infarction, scar and fibrosis. In addition to laying out the strengths and weaknesses of each modality, the reader will be introduced to rapid developments in T1 and T2 mapping as well as the use of contrast-derived extracellular volume for quantification of diffuse fibrosis.

Work-related peak flow and asthma symptoms in a damp building.

BACKGROUND: Working in damp conditions is associated with asthma, but few studies have used objective testing to document work-related patterns. AIMS: To describe the relationship of peak flow measurements to work-related asthma (WRA) symptoms and WRA among occupants in a damp office building. METHODS: At the beginning of the study, all workers were offered a questionnaire and methacholine challenge testing. Participants were then instructed to perform serial spirometry using handheld spirometers five times per day over a 3 week period. Peak flow data were analysed using OASYS-2 software. We calculated the area between the curves (ABC score) using hours from waking. We considered a score >5.6 L/min/h to be indicative of a work-related pattern. RESULTS: All 24 employees participated in the questionnaire. Seven participants (29%) reported physician-diagnosed asthma with onset after starting work in the building. Almost two-thirds (63%) of participants reported at least one lower respiratory symptom (LRS) occurring one or more times per week in the last 4 weeks. Twenty-two (92%) consented to participate in serial spirometry. Fourteen participants had adequate quality of serial spirometry, five of whom had ABC scores >5.6, ranging from 5.9-23.0. Of these five, two had airways responsiveness, three had current post-hire onset physician-diagnosed asthma and four reported work-related LRS. CONCLUSIONS: We found evidence of work-related changes in serial peak flows among some occupants of an office building with a history of dampness. Serial peak flows may be a useful measure to determine WRA in office settings.

16alpha-Bromoepiandrosterone (HE2000) limits non-productive inflammation and stimulates immunity in lungs.

16alpha-Bromoepiandrosterone (HE2000) is a synthetic steroid that limits non-productive inflammation, enhances protective immunity and improves survival in clinical studies of patients with human immunodeficiency virus (HIV), malaria and tuberculosis infections. We now show that HE2000 decreased nitric oxide production by lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Treatment with HE2000 also reduced non-productive inflammation associated with carrageenan-induced pleurisy and LPS-induced lung injury in mice. In the hapten-carrier reporter antigen popliteal lymph node assay, HE2000 increased absolute numbers of lymphocytes, antigen-presenting cells, hapten-specific immunoglobulin (Ig)M antibody-forming cells and shifted the interferon (IFN)-gamma/interleukin (IL)-4 balance towards IFN-gamma production. In the cystic fibrosis transmembrane conductance regulator (CFTR(-/-)) mouse model of acute Pseudomonas aeruginosa infection, treatment with HE2000 consistently reduced bacterial burden in lungs. All HE2000 effects were dose-dependent. In H1N1 infection in mice, HE2000 was safe but not effective as a monotherapy, as treatment did not effect survival. HE2000 reduced mortality related to excessive inflammation and opportunistic lung infections in animals and patients, and this might extend to those with H1N1 influenza infection.

Respiratory inflammatory responses among occupants of a water-damaged office building.

UNLABELLED: The National Institute for Occupational Safety and Health (NIOSH) received a request for evaluation of a water-damaged office building which housed approximately 1300 employees. Workers reported respiratory conditions that they perceived to be building related. We hypothesized that these symptoms were associated with airways inflammation. To test this hypothesis, we assessed airways inflammation in employees using exhaled breath condensate (EBC) and the fraction of exhaled nitric oxide (FENO). In September 2001, a health questionnaire was offered to all employees. Based on this questionnaire, NIOSH invited 356 symptomatic and asymptomatic employees to participate in a medical survey. In June 2002, these employees were offered questionnaire, spirometry, methacholine challenge test, allergen skin prick testing, EBC and FENO. FENO or EBC were completed by 239 participants. As smoking is highly related to the measurements that we used in this study, we included only the 207 current non-smokers in the analyses. EBC interleukin-8 (IL-8) levels, but not nitrite, were significantly higher among workers with respiratory symptoms and in the physician-diagnosed asthmatic group. Of the analyses assessed, EBC IL-8 showed the most significant relationship with a number of symptoms and physician-diagnosed asthma. PRACTICAL IMPLICATIONS: Implementation of exhaled breath condensate and exhaled nitric oxide in indoor air quality problems.

Management of epilepsy in women.

There are many aspects to the management of epilepsy in women related to their role in reproduction. Some of these need to be considered in adolescents, some are related to pregnancy, concerning both the mother and her infant, and others with the menstrual cycle and the menopause. This review considers contraception, fertility, teratogenicity, and the use of folic acid. It also discusses the special investigations in pregnancy, hyperemesis, the effect of pregnancy on the control of epilepsy, the effect of seizures on the fetus, a first fit in pregnancy, pseudoseizures, seizures during delivery, vitamin K, breast feeding, postpartum maternal epilepsy, hereditary risks, counselling, catamenial epilepsy, the menopause, and bone density.

Synthesis of C-11 methyl-substituted benzocycloheptapyridine inhibitors of farnesyl protein transferase.

[formula: see text] Synthesis of C-11 methyl-substituted benzocycloheptylpyridine tricyclic compounds has been achieved via two different methods. Methylation of C-11 has been effected by treatment of amine 4 with BuLi followed by Mel quenching. In a similar procedure, introduction of a C-11 substituent with concomitant rearrangement of the exocyclic double bond has been carried out. Potent farnesyl protein transferase inhibitors have been synthesized using the above methodologies.

Arrhythmia detection and response in a monitoring technician and pocket paging system.

Technologically advanced telemetry systems have begun to produce alternatives to the need for continuous visual observation of the electrocardiogram (ECG). Few studies have been conducted to determine the efficacy of these systems in the clinical setting. The purpose of this study was to describe two different approaches to communication of arrhythmia events and corresponding nurse response. One approach, on a cardiac medical unit, utilized a monitoring technician to continuously observe ECGs at a central monitoring technician station (MTS) and notify the nurse of changes. The other approach, on a general medical unit, eliminated the use of the monitoring technician and utilized a pocket paging system (PPS). The PPS interfaced with the computerized arrhythmia detection system from the ECG monitor, which directly alerted the nurse to arrhythmia events. A quasi-experimental comparative post-test design was used. The sample consisted of 50 randomly selected, 2-hour observation periods on each unit during a 3-month period. Data collectors recorded the interaction of the monitoring technician with the arrhythmia detection system and the nurse on the MTS unit, or the nurse using the PPS. Results of this study revealed all arrhythmia events activated an alarm by the computerized arrhythmia detection system. Length of time to notify the nurse was within 0 to 1 minute for both systems. This study demonstrated that the PPS is a viable approach to arrhythmia detection and communication in the medical/cardiac patient population.

The physician's role in minimizing prehospital delay in patients at high risk for acute myocardial infarction: recommendations from the National Heart Attack Alert Program. Working Group on Educational Strategies To Prevent Prehospital Delay in Patients at High Risk for Acute Myocardial Infarction.

Physicians and other health care professionals play an important role in reducing the delay to treatment in patients who have an evolving acute myocardial infarction. A multidisciplinary working group has been convened by the National Heart Attack Alert Program (which is coordinated by the National Heart, Lung, and Blood Institute of the National Institutes of Health) to address this concern. The working group's recommendations target specific groups of patients: those who are known to have coronary heart disease, atherosclerotic disease of the aorta or peripheral arteries, or cerebrovascular disease. The risk for acute myocardial infarction or death in such patients is five to seven times greater than that in the general population. The working group recommends that these high-risk patients be clearly informed about symptoms that they might have during a coronary occlusion, steps that they should take, the importance of contacting emergency medical services, the need to report to an appropriate facility quickly, treatment options that are available if they present early, and rewards of early treatment in terms of improved quality of life. These instructions should be reviewed frequently and reinforced with appropriate written material, and patients should be encouraged to have a plan and to rehearse it periodically. Because of the important role of the bystander in increasing or decreasing delay to treatment, family members and significant others should be included in all instruction. Finally, physicians' offices and clinics should devise systems to quickly assess patients who telephone or present with symptoms of a possible acute myocardial infarction.

Hyperthermic intraoperative intraperitoneal chemotherapy safety considerations.

Perioperative staff members encounter many occupational exposure hazards in the workplace. Cytotoxic agent exposure is a relatively new hazard that perioperative staff members are experiencing as more surgeons use hyperthermic intraoperative intraperitoneal chemotherapy (HIIC) to treat patients with abdominopelvic cavity malignancies. Routes of exposure include inhalation, ingestion, injection, and skin contact. The National Cancer Institute, the Occupational Safety and Health Administration, and the Joint Commission on Accreditation of Healthcare Organizations provide guidelines for the safe administration and handling of cytotoxic agents. Institutions in which cytotoxic agents are administered should use these guidelines to develop policies, procedures, and educational programs to protect surgical patients and perioperative staff members.

Safety constiderations in the use of intraoperative intraperitoneal chemotherapy.

The clinical significance of occupational exposure to antineoplastic agents is controversial. Accrued evidence does not seem to indicate mutagenicity, carcinogenicity, and tertogenicity when exposure is limited by proper precautions. However, medical surveillance of personnel continually exposed to these cytotoxic agents will aid in early detection of any problems should they occur. Because the current fiscal milieu constantly emphasizes cost containment, true prevention means an intense worker education program. Personnel continually exposed to these cytotoxic agents should have scheduled health checkups twice a year, and exposure frequency should be reported to the employee's personal physician.

Supporting nursing innovations in a cost-conscious environment.

Our rapidly changing health care environment requires critical care nurses to develop creative and innovative approaches to patient care. Empowering and enabling these nurses are the only ways that health care institutions will be able to meet the challenges of the future. This article describes two examples of innovations that have contributed to cost containment within a coronary care unit.

Synthesis and structure-activity relationships of novel retinoid X receptor-selective retinoids.

Two series of potent retinoid X receptor (RXR)-selective compounds were designed and synthesized based upon recent observation that (E)-4-[2-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthalenyl)-1- propenyl]benzoic acid (TTNBP) binds and transactivates only the retinoic acid receptor (RAR) subtypes whereas (E)-4-[2-(3,5,5,8,8-pentamethyl-5,6,7,8- tetrahydro-2-naphthalenyl)-1-propenyl]benzoic acid (3-methyl TTNPB) binds and transactivates both the RAR and RXR subfamilies. Addition of functional groups such as methyl, chloro, bromo, or ethyl to the 3 position of the tetrahydronaphthalene moiety of 4-[(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)carbonyl]benzoic acid (5a) and 4-[1-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2- naphthyl)ethenyl]benzoic acid (6a) results in compounds which elicit potent and selective activation of the RXR class. Such RXR-selective compounds offer pharmacological tools for elucidating the biological role of the individual retinoid receptors with which they interact. Activation profiles in cotransfection and competitive binding assays as well as molecular modeling calculations demonstrate critical structural determinants that confer selectivity for members of the RXR subfamily. The most potent compound of these series, 4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)ethenyl]ben zoi c acid (6b), is the first RXR-selective retinoid (designated as LGD1069) to enter clinical trials for cancer indications.

Synthesis of high specific activity [3H]-9-cis-retinoic acid and its application for identifying retinoids with unusual binding properties.

all-trans-Retinoic acid is known to bind to the retinoic acid receptors (RARs) resulting in an increase in their transcriptional activity. In contrast, recently identified 9-cis-retinoic acid (9-cis-RA), which is an additional endogenous RA isomer, is capable of binding to both RARs and retinoid X receptors (RXRs). These distinct properties have raised questions as to the biological role governed by these two retinoic acid isomers and the set of target genes that they regulate. Herein, we report the synthesis of high specific activity [3H]-9-cis-RA and its application to study the ligand-binding properties of the various retinoid receptor subtypes. We examined the binding properties of RARs and RXRs for a series of synthetic retinoids and compared the ligand-binding properties of these arotinoid analogs with their ability to regulate gene expression via the retinoid receptors in a cotransfection assay. The utilization of the [3H]-9-cis-RA competitive binding assay and the cotransfection assay has made it possible to rapidly identify important structural features of retinoids leading to increased selectivity for either the RAR or RXR receptor subtypes.

Transactivation properties of retinoic acid and retinoid X receptors in mammalian cells and yeast. Correlation with hormone binding and effects of metabolism.

The binding affinities of 9-cis-retinoic acid (9-cis-RA) and all-trans-retinoic acid (t-RA) for retinoic acid receptors (RAR) alpha, beta, and gamma and for retinoid X receptors (RXR) alpha, beta, and gamma were determined using the recombinant receptor proteins and were compared with each hormone's ability to activate transcription through the receptors in mammalian and yeast cell systems. 9-cis-RA bound to both the RXRs (Kd values = 1.4-2.4 nM) and the RARs (Kd values = 0.2-0.8 nM). The ability of 9-cis-RA to bind to the RARs and RXRs correlated with its ability to produce similar transactivation profiles with these receptors in mammalian and yeast cell assays. t-RA bound to the RARs (Kd values = 0.2-0.4 nM) and activated transcription through the RARs in mammalian and yeast cells. In contrast, while t-RA did not bind to the RXRs, it did activate the RXRs, albeit less potently than 9-cis-RA, in mammalian cells. In yeast, however, the RXRs activated transcription only in the presence of 9-cis-RA, not with t-RA. While RAR gamma is activated in yeast by either t-RA or 9-cis-RA, the overall level of transcription was increased upon the addition of hormone-occupied RXR. Metabolism studies suggest that while there was no cell-dependent interconversion between t-RA and 9-cis-RA in yeast, there was cell-dependent conversion of 9-cis-RA to t-RA in mammalian cells [corrected].