Persistent effects of Libby amphibole and amosite asbestos following subchronic inhalation in rats.

BACKGROUND: Human exposure to Libby amphibole (LA) asbestos increases risk of lung cancer, mesothelioma, and non-malignant respiratory disease. This study evaluated potency and time-course effects of LA and positive control amosite (AM) asbestos fibers in male F344 rats following nose-only inhalation exposure. METHODS: Rats were exposed to air, LA (0.5, 3.5, or 25.0 mg/m(3) targets), or AM (3.5 mg/m(3) target) for 10 days and assessed for markers of lung inflammation, injury, and cell proliferation. Short-term results guided concentration levels for a stop-exposure study in which rats were exposed to air, LA (1.0, 3.3, or 10.0 mg/m(3)), or AM (3.3 mg/m(3)) 6 h/day, 5 days/week for 13 weeks, and assessed 1 day, 1, 3, and 18 months post-exposure. Fibers were relatively short; for 10 mg/m(3) LA, mean length of all structures was 3.7 µm and 1% were longer than 20 µm. RESULTS: Ten days exposure to 25.0 mg/m(3) LA resulted in significantly increased lung inflammation, fibrosis, bronchiolar epithelial cell proliferation and hyperplasia, and inflammatory cytokine gene expression compared to air. Exposure to 3.5 mg/m(3) LA resulted in modestly higher markers of acute lung injury and inflammation compared to AM. Following 13 weeks exposure, lung fiber burdens correlated with exposure mass concentrations, declining gradually over 18 months. LA (3.3 and 10.0 mg/m(3)) and AM produced significantly higher bronchoalveolar lavage markers of inflammation and lung tissue cytokines, Akt, and MAPK/ERK pathway components compared to air control from 1 day to 3 months post-exposure. Histopathology showed alveolar inflammation and interstitial fibrosis in all fiber-exposed groups up to 18 months post-exposure. Positive dose trends for incidence of alveolar epithelial hyperplasia and bronchiolar/alveolar adenoma or carcinoma were observed among LA groups. CONCLUSIONS: Inhalation of relatively short LA fibers produced inflammatory, fibrogenic, and tumorigenic effects in rats which replicate essential attributes of asbestos-related disease in exposed humans. Fiber burden, inflammation, and activation of growth factor pathways may persist and contribute to lung tumorigenesis long after initial LA exposure. Fiber burden data are being used to develop a dosimetry model for LA fibers, which may provide insights on mode of action for hazard assessment.

An integrated mental health clinical rotation.

The most common site for accessing mental health care is the primary care setting. Yet, primary care nurses are not adequately prepared to treat the complex mental health needs of these patients. Similarly, providers in segregated mental health sites do not adequately address physical health needs. New educational models are needed to better prepare nursing graduates to provide holistic care. The integrated mental health model, which colocates mental health specialists in primary care sites, is designed to do this. This article describes key curricular elements of a successful interprofessional clinical rotation within an integrated mental health team that included the use of case studies, a standardized mental health screening instrument, a quality improvement process, and a patient satisfaction questionnaire. Family nurse practitioner and psychiatric mental health nurse practitioner students learned to collaborate with each other and with other members of the interprofessional team to provide holistic care.

What factors affect medication-storage practice among patients on methadone maintenance treatment?

OBJECTIVES: Medication storage in patients' homes is an important safety issue. Safe storage of methadone oral solution is of particular concern. Previous studies have suggested that only about half of patients store methadone appropriately. The aims of this study were to describe medication-storage practice in a sample of patients receiving methadone maintenance treatment (MMT), and to identify factors associated with safe storage. METHODS: The setting was a primary health care centre in Edinburgh, Scotland. One hundred and four consecutive patients on MMT completed a self-administered questionnaire covering medication-storage practice, together with clinical and demographic variables. Storage of medication was classified as 'acceptable' if medication was out of sight and out of reach of children, and 'optimal' if it was also kept in a secure container. KEY FINDINGS: Percentages (95% confidence intervals) for acceptable and optimal storage were as follows: methadone 80% (71-86%) and 33% (24-42%); other prescribed medication 69% (59-78%) and 27% (19-37%); purchased medication 64% (50-76%) and 28% (17-42%). Safe storage of methadone was more common in patients taking higher doses of methadone (P = 0.004 for acceptable storage, and P = 0.012 for optimal storage), and in those with children in the house (P = 0.007 and 0.061). Safe storage of prescribed and purchased medication was strongly associated with safe storage of methadone (P < 0.01 in both cases). CONCLUSIONS: Medication-storage practice was better than in previous surveys of patients on MMT. This may reflect the high profile given to safety issues for children of drug-using parents in Scotland, as well as local initiatives. Some aspects of prescribing and dispensing practice could be improved further.

What factors affect medication-storage practice among patients on methadone maintenance treatment?

OBJECTIVES: Medication storage in patients' homes is an important safety issue. Safe storage of methadone oral solution is of particular concern. Previous studies have suggested that only about half of patients store methadone appropriately. The aims of this study were to describe medication-storage practice in a sample of patients receiving methadone maintenance treatment (MMT), and to identify factors associated with safe storage. METHODS: The setting was a primary health care centre in Edinburgh, Scotland. One hundred and four consecutive patients on MMT completed a self-administered questionnaire covering medication-storage practice, together with clinical and demographic variables. Storage of medication was classified as 'acceptable' if medication was out of sight and out of reach of children, and 'optimal' if it was also kept in a secure container. KEY FINDINGS: Percentages (95% confidence intervals) for acceptable and optimal storage were as follows: methadone 80% (71-86%) and 33% (24-42%); other prescribed medication 69% (59-78%) and 27% (19-37%); purchased medication 64% (50-76%) and 28% (17-42%). Safe storage of methadone was more common in patients taking higher doses of methadone (P = 0.004 for acceptable storage, and P = 0.012 for optimal storage), and in those with children in the house (P = 0.007 and 0.061). Safe storage of prescribed and purchased medication was strongly associated with safe storage of methadone (P < 0.01 in both cases). CONCLUSIONS: Medication-storage practice was better than in previous surveys of patients on MMT. This may reflect the high profile given to safety issues for children of drug-using parents in Scotland, as well as local initiatives. Some aspects of prescribing and dispensing practice could be improved further.

Community perceptions of mental health needs in an underserved minority neighborhood.

Accurate information is needed to facilitate health equity in underserved communities. This community-based participatory study asked residents about the meaning of mental health, their perceptions of community mental health needs, barriers to accessing mental health care, and acceptability of mental health services that are integrated in primary health clinics. Forty-five primarily African-American residents from urban communities participated in focus groups. Findings revealed high prevalence of substance abuse, depression, crime, and stigma about mental illness, with multiple access barriers. Participants were receptive to mental health care integrated in primary care, if others did not know they were receiving mental health care.

Genotoxicity of intermittent co-exposure to benzene and toluene in male CD-1 mice.

Benzene is an important industrial chemical. At certain levels, benzene has been found to produce aplastic anemia, pancytopenia, myeloblastic anemia and genotoxic effects in humans. Metabolism by cytochrome P450 monooxygenases and myeloperoxidase to hydroquinone, phenol, and other metabolites contributes to benzene toxicity. Other xenobiotic substrates for cytochrome P450 can alter benzene metabolism. At high concentrations, toluene has been shown to inhibit benzene metabolism and benzene-induced toxicities. The present study investigated the genotoxicity of exposure to benzene and toluene at lower and intermittent co-exposures. Mice were exposed via whole-body inhalation for 6h/day for 8 days (over a 15-day time period) to air, 50 ppm benzene, 100 ppm toluene, 50 ppm benzene and 50 ppm toluene, or 50 ppm benzene and 100 ppm toluene. Mice exposed to 50 ppm benzene exhibited an increased frequency (2.4-fold) of micronucleated polychromatic erythrocytes (PCE) and increased levels of urinary metabolites (t,t-muconic acid, hydroquinone, and s-phenylmercapturic acid) vs. air-exposed controls. Benzene co-exposure with 100 ppm toluene resulted in similar urinary metabolite levels but a 3.7-fold increase in frequency of micronucleated PCE. Benzene co-exposure with 50 ppm toluene resulted in a similar elevation of micronuclei frequency as with 100 ppm toluene which did not differ significantly from 50 ppm benzene exposure alone. Both co-exposures - 50 ppm benzene with 50 or 100 ppm toluene - resulted in significantly elevated CYP2E1 activities that did not occur following benzene or toluene exposure alone. Whole blood glutathione (GSH) levels were similarly decreased following exposure to 50 ppm benzene and/or 100 ppm toluene, while co-exposure to 50 ppm benzene and 100 ppm toluene significantly decreased GSSG levels and increased the GSH/GSSG ratio. The higher frequency of micronucleated PCE following benzene and toluene co-exposure when compared with mice exposed to benzene or toluene alone suggests that, at the doses used in this study, toluene can enhance benzene-induced clastogenic or aneugenic bone marrow injury. These findings exemplify the importance of studying the effects of binary chemical interactions in animals exposed to lower exposure concentrations of benzene and toluene on benzene metabolism and clastogenicity. The relevance of these data on interactions for humans exposed at low benzene concentrations can be best assessed only when the mechanism of interaction is understood at a quantitative level and incorporated within a biologically based modeling framework.

Interprofessional ambulatory primary care practice-based educational program.

Although interprofessional teamwork and collaboration are considered key elements for improving patient outcomes, there are few reports of controlled studies involving interprofessional training of health care learners in the ambulatory primary care setting. We describe an educational program for teams of nurse practitioners, family medicine residents and social work students to work together at clinical sites in the delivery of longitudinal care in primary care ambulatory clinics. Year 1 was a planning year. Program evaluation completed at the end of the second curriculum (Year 3) indicated that the changes the team made at the end of the first curriculum (Year 2) resulted in increased appreciation of the training program, greater perception of value of care delivered by interprofessional teams among team learners as compared to non-team learners, and team learner self assessment of improved team skills including working with other professionals, resolving conflict, and integrating prevention and health promotion into health care. Team learners demonstrated an increased awareness of the limits of their own profession's approach to team care. We conclude that interprofessional ambulatory clinical training in primary care where learners work together providing care to patients can contribute to fostering both positive learner attitudes toward interprofessional work and development of team skills.

Incorporation of tissue reaction kinetics in a computational fluid dynamics model for nasal extraction of inhaled hydrogen sulfide in rats.

Rodents exposed to hydrogen sulfide (H2S) develop olfactory neuronal loss. This lesion has been used by the risk assessment community to develop occupational and environmental exposure standards. A correlation between lesion locations and areas of high H2S flux to airway walls has been previously demonstrated, but a quantitative dose assessment is needed to extrapolate dose at lesion sites to humans. In this study, nasal extraction (NE) of 10, 80, and 200 ppm H2S was measured in the isolated upper respiratory tract of anesthetized rats under constant unidirectional inspiratory flow rates of 75, 150, and 300 ml/min. NE was dependent on inspired H2S concentration and air flow rate: increased NE was observed when H2S exposure concentrations or inspiratory air flow rates were low. An anatomically accurate, three-dimensional computational fluid dynamics (CFD) model of rat nasal passages was used to predict NE of inhaled H2S. To account for the observed dependence of NE on H2S exposure concentration, the boundary condition used at airway walls incorporated first-order and saturable kinetics in nasal tissue to govern mass flux at the air:tissue interface. Since the kinetic parameters cannot be obtained using the CFD model, they were estimated independently by fitting a well-mixed, two-compartment pharmacokinetic (PK) model to the NE data. Predicted extraction values using this PK-motivated CFD approach were in good agreement with the experimental measurements. The CFD model provides estimates of localized H2S flux to airway walls and can be used to calibrate lesion sites by dose.

A millennial benchmark of nurse-academics' scholarly productivity.

The benchmark against which nurse-academics are primarily judged remains scholarly productivity. This study sought to examine levels of scholarly productivity amongst Australian nurse academics: where they are putting their emphasis, and what progress they are making. This quantitative study used a questionnaire survey technique that identified individual items of scholarship over a two-year period. The use of two author-developed rating scales, the General Scholarship Index (GSI) and the DEST Scholarship Index (DSI) enabled a comparison of nurse academics with other academic disciplines. Findings from the study underscore the positive association between academic rank, qualifications and scholarly productivity. To facilitate increasing the latter to a level comparable with other disciplines, nurse academics may need to refocus their energies on DEST approved activities. A work climate more conducive to fostering the ethos and skills of academic scholarly productivity is needed.

Nurse-academics' mentorship: rhetoric or reality?

Mentorship is generally identified in nursing literature as a positive strategy, and one that is said to be beneficial in increasing scholarly productivity. However, previous studies investigating the relationship of mentoring to scholarly productivity have produced equivocal findings. This relationship was examined as part of a study that considered constraints and/or facilitators of scholarly productivity among nurse academics. A survey questionnaire technique was used to establish current scholarly productivity levels, and frame and factor facilitating theory and analysis to identify major constraints and facilitators. Findings showed that while the majority of participants perceived mentoring as important to developing and increasing scholarly productivity, this was less so as academic rank increased. More than a quarter reported never having had a mentor. The burden of teaching and administrative over-load, and a cultural climate of non-support, were described as major disincentives to mentoring. Mentoring was more likely to occur where a collaborative and collegial network to support scholarly productivity existed. However, often it was seen as not available. A workplace environment that is appropriately supported by adequate resources may be as important as the research training that can occur through mentoring.

Nurse-academics' scholarly productivity: perceived frames and facilitators.

The reward system within Universities remains focused on research, with a benchmark of scholarly productivity, especially in relation to promotion. Despite their relative newness to the tertiary system, nurse academics are judged by the same standards as other disciplines. This study sought to examine factors that constrained and/or facilitated scholarly productivity. The study used a questionnaire survey technique to establish current productivity levels, and frame and facilitating factor theory and analysis to identify major constraints and facilitators. Findings from the study were that the unremitting nature of teaching, course coordination and university service workloads interact to the detriment of research and writing. Facilitating factors included a departmental culture that values and supports research, in conjunction with tangible support from University management. Mentorship was viewed as desirable, but often not available. An environment that more actively prioritises, fosters and supports academic scholarly productivity is needed.

The interrater reliability among physical therapists newly trained in a classification system for acute low back pain.

STUDY DESIGN: A prospective methodological interrater reliability study. OBJECTIVES: To calculate the interrater reliability among clinicians newly trained in a classification system for acute low back pain and to determine the level of agreement at key junctures within the classification algorithm. BACKGROUND: The utility of a classification system for patients with low back pain depends on its reliability and generalizability. To be practical, clinicians must be able to apply the system after a reasonable amount of training. Identifying key points in the classification algorithm where disagreement occurs can lead to better operational definitions. METHODS: Four physical therapists read an article and attended a 1-day training session in the classification system. Randomly paired therapists classified patients referred for treatment of acute low back pain and noted decisions at key junctures in the system algorithm. RESULTS: Forty-five patients were classified. Repeated examinations did not increase the patient's pain (P>.05). For 3 out of the 4 therapists, the interrater reliability showed a kappa value of 0.45. The fourth therapist, excluded from the overall analysis, exhibited a bias towards the immobilization classification. Among the 3 therapists, major disagreement occurred with the determination of symmetry with trunk side bending and the effects of repeated movements. CONCLUSIONS: Three out of 4 clinicians newly trained in the system showed moderate reliability. The reliability was slight when the fourth therapist was included. Refinement of the operational definitions and criteria for determining lumbar capsular patterns are needed. One day of training is probably not adequate for all therapists, especially for those biased towards specific low back pain syndromes.

Pharmacy customers' views and experiences of using pharmacies which provide drug misuse services.

This study aimed to determine whether pharmacy customers are deterred from using a pharmacy that offers services to drug misusers. If patients are deterred, what are their specific concerns? The study was qualitative and three different groups were interviewed about their views on pharmacies providing services to drug misusers (i) pharmacy customers, (ii) local community councils and (iii) local drug forums. This paper focuses on pharmacy customer interview results. Interviews were conducted in 10 pharmacies, five in Aberdeen and five in Glasgow, both areas of high drug misuse. The pharmacy customers were attending pharmacies with high, medium and low involvement with drug misusers and were located in city centre, suburban and rural locations. Pharmacy customers were generally supportive of pharmacies offering services to drug misusers. However, their support was often qualified by a wish to see a private area provided for methadone consumption. Pharmacy customers were more knowledgeable of the rationale for and supportive of needle exchange services compared to methadone maintenance and supervised consumption. The results of the study demonstrate that the majority of pharmacy customers are supportive of drug misuse services, provided there is adequate privacy in the pharmacy. These results should be used to encourage more pharmacists to provide drug misuse services.

A comprehensive system of pharmaceutical care for drug misusers.

This article outlines the evolution of a community pharmacy-based supervised consumption of methadone program in Grater Glasgow. The formalization of this program in 1994 promoted full patient compliance with the methadone regimen and reduced seepage of the drug to the illicit market. 184 of the area's 215 community pharmacies now dispense methadone for the treatment of opiate dependence. Of these, 173 have a supplementary contract with the local health board to supervise the consumption of methadone on their premises. In addition 15 of "methadone" pharmacists are involved in the provision of a pharmacy based needle exchange scheme. This has been shown to be the most efficient and cost effective method of delivering clean injecting equipment to injecting drug users in the Greater Glasgow area. Glasgow's pharmacists' have now been involved in the methadone and needle exchange programs for more than ten years. The support needed by pharmacists and the steps that have been put in place to provide this level of commitment are described. The development of the Glasgow pharmacy based services to drug users has had a major impact on practice elsewhere in the United Kingdom.

Genetic susceptibility to benzene-induced toxicity: role of NADPH: quinone oxidoreductase-1.

Enzymes that activate and detoxify benzene are likely genetic determinants of benzene-induced toxicity.NAD(P)H: quinone oxidoreductase-1 (NQO1) detoxifies benzoquinones, proposed toxic metabolites of benzene. NQO1 deficiency in humans is associated with an increased risk of leukemia, specifically acute myelogenous leukemia, and benzene poisoning. We examined the importance of NQO1 in benzene-induced toxicity by hypothesizing that NQO1-deficient (NQO1-/-) mice are more sensitive to benzene than mice with wild-type NQO1 (NQO1+/+; 129/Sv background strain). Male and female NQO1-/- and NQO1+/+ mice were exposed to inhaled benzene (0, 10, 50, or 100 ppm) for 2 weeks, 6 h/day, 5 days/week. Micronucleated peripheral blood cells were counted to assess genotoxicity. Peripheral blood counts and bone marrow histology were used to assess hematotoxicity and myelotoxicity. p21 mRNA levels in bone marrow cells were used as determinants of DNA damage response. Female NQO1-/- mice were more sensitive (6-fold) to benzene-induced genotoxicity than the female NQO1+/+ mice. Female NQO1-/- mice had a 9-fold increase (100 versus 0 ppm) in micronucleated reticulocytes compared with a 3-fold increase in the female NQO1+/+ mice. However, the induced genotoxic response in male mice was similar between the two genotypes (> or = 10-fold increase at 100 ppm versus 0 ppm). Male and female NQO1-/- mice exhibited greater hematotoxicity than NQO1+/+ mice. p21 mRNA levels were induced significantly in male mice (>10-fold) from both strains and female NQO1-/- mice (> 8-fold), which indicates an activated DNA damage response. These results indicate that NQO1 deficiency results in substantially greater benzene-induced toxicity. However, the specific patterns of toxicity differed between the male and female mice.

Olfactory transport: a direct route of delivery of inhaled manganese phosphate to the rat brain.

Experiments examining the dosimetry of inhaled manganese generally focus on pulmonary deposition and subsequent delivery of manganese in arterial blood to the brain. Growing evidence suggests that nasal deposition and transport along olfactory neurons represents another route by which inhaled manganese is delivered to certain regions of the rat brain. The purpose of this study was to evaluate the olfactory uptake and direct brain delivery of inhaled manganese phosphate ((54)MnHPO(4)). Male, 8-wk-old, CD rats with either both nostrils patent or the right nostril occluded underwent a single, 90-min, nose-only exposure to a (54)MnHPO(4) aerosol (0.39 mg (54)Mn/m(3); MMAD 1.68 microm, sigma(g) 1.42). The left and right sides of the nose, olfactory pathway, striatum, cerebellum, and rest of the brain were evaluated immediately after the end of the (54)MnHPO(4) exposure and at 1, 2, 4, 8, and 21 d postexposure with gamma spectrometry and autoradiography. Rats with two patent nostrils had equivalent (54)Mn concentrations on both sides of the nose, olfactory bulb, and striatum, while asymmetrical (54)Mn delivery occurred in rats with one occluded nostril. High levels of (54)Mn activity were observed in the olfactory bulb and tubercle on the same side (i.e., ipsilateral) to the open nostril within 1-2 d following (54)MnHPO(4) exposure, while brain and nose samples on the side ipsilateral to the nostril occlusion had negligible levels of (54)Mn activity. Our results demonstrate that the olfactory route contributes to (54)Mn delivery to the rat olfactory bulb and tubercle. However, this pathway does not significantly contribute to striatal (54)Mn concentrations following a single, short-term inhalation exposure to (54)MnHPO(4).

Over a decade of syringe exchange: results from 1997 UK survey.

AIMS: To describe syringe exchange provision in the United Kingdom. DESIGN: Two-phase cross-sectional survey: phase I, establishing a sampling frame of syringe exchange coordinators (n=420); phase II, surveying the coordinators seeking data on the number of syringe exchange outlets, visits and syringes distributed during April 1997 (68% response rate). SETTING: United Kingdom. FINDINGS: In 1997, nearly all Health Authorities in the United Kingdom (96%) operated some form of syringe exchange service, except Northern Ireland. In April 1997, 1 707 000 syringes were reported as being distributed. Assuming that non-responders coordinated the median number of outlets and distributed the median number of syringes as responders, we estimate that 27 million syringes were distributed annually from over 2000 outlets in the United Kingdom. The number distributed in Scotland was 3-4 times less than in England when measured as a number per adult (15-44), drug user in treatment, or estimated injecting drug user. CONCLUSIONS: Overall, there has been a 6.5-fold increase in syringe distribution in England since 1991. The number of syringes distributed in the United Kingdom may be higher than the United States. However, there appears to be unequal distribution of syringes within the United Kingdom, which may be associated with higher levels of HCV among injectors in Scotland compared to England.

From apprentices to academics: are nurses catching up?

In comparison to other disciplines, Australian nursing has only come relatively lately to academia. Traditionally, academic qualifications were not viewed as necessary for nurses. The movement of nursing education to the tertiary sector has seen many changes from the traditional apprenticeship model and the characteristics of nurse-academics reflect these. The researchers identified changes that have occurred in the last five years in nurse-academics' qualifications, academic rank and links between them. It is clear that the goalposts for nurse academics have moved, with a master's degree now standard for Lecturer Level B and a doctorate for Level D. Other findings show a strong link between movement (transfer), increased qualifications and promotion. Females were more likely than males to have increased their qualifications and to be promoted. In terms of academic qualifications in the whole system, female nurse-academics have caught up with their counterparts in the former CAE sector. Male nurse-academics have parity with female nurse-academics but not with males in the system generally. The study shows the great strides that Australian nurse-academics have made in the five years preceding the end of the old millenium but illustrates that they and female academics generally have not yet caught up to their male colleagues.