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Background: One explanation for why older age is associated with greater duration of wage replacement following a work-related injury may be that older workers sustain more severe injuries and different types of injury compared with their younger counterparts. Aims: To examine the role of injury-related characteristics in explaining the impact of age on wage replacement duration, and whether the relationship between age and wage replacement duration is consistent across injury types and levels of severity. Methods: A secondary analysis of workers' compensation claims in the Australian state of Victoria. In Victoria, only injuries which have accumulated >10 days of wage replacement, or have health care expenditures above a financial threshold, are eligible for compensation. Nested regression models were used to examine the relative contribution of injury-related characteristics to age differences in wage replacement duration. Results: Older age was associated with greater days of wage replacement among men and women, even after adjusting for injury characteristics. Adjustment for differences in injury types and compensation reporting practices resulted in moderate attenuation of the age-duration relationship among men and small attenuation among women. The age-duration relationship was consistent across injury types/severity. Conclusions: The relationship between older age and greater duration of wage replacement is ubiquitous across injuries of different types and severity. Future research is required to understand better why older age is consistently associated with worse compensation outcomes following work-related injury. [ABSTRACT FROM AUTHOR]

Background: Despite disproportionate rates of mental ill-health compared with non-Indigenous populations, few programs have been tailored to the unique health, social, and cultural needs and preferences of young Aboriginal and Torres Strait Islander males. This paper describes the process of culturally adapting the US-based Young Black Men, Masculinities, and Mental Health (YBMen) Project to suit the needs, preferences, culture, and circumstances of Aboriginal and Torres Strait Islander males aged 16-25 years in the Northern Territory, Australia. YBMen is an evidence-based social media-based education and support program designed to promote mental health, expand understandings of gender and cultural identities, and enhance social support in college-aged Black men., Methods: Our adaptation followed an Extended Stages of Cultural Adaptation model. First, we established a rationale for adaptation that included assessing the appropriateness of YBMen's core components for the target population. We then investigated important and appropriate models to underpin the adapted program and conducted a non-linear, iterative process of gathering information from key sources, including young Aboriginal and Torres Strait Islander males, to inform program curriculum and delivery., Results: To maintain program fidelity, we retained the core curriculum components of mental health, healthy masculinities, and social connection and kept the small cohort, private social media group delivery but developed two models: 'online only' (the original online delivery format) and 'hybrid in-person/online' (combining online delivery with weekly in-person group sessions). Adaptations made included using an overarching Aboriginal and Torres Strait Islander social and emotional wellbeing framework and socio-cultural strengths-based approach; inclusion of modules on health and wellbeing, positive Indigenous masculinities, and respectful relationships; use of Indigenous designs and colours; and prominent placement of images of Aboriginal and Torres Strait Islander male sportspeople, musicians, activists, and local role models., Conclusions: This process resulted in a culturally responsive mental health, masculinities, and social support health promotion program for young Aboriginal and Torres Strait Islander males. Next steps will involve pilot testing to investigate the adapted program's acceptability and feasibility and inform further refinement., (© 2024. The Author(s).)

Although highly related, mental illness may not fully determine perceived well-being, a distinction captured by dual-continuum models. Separating mental illness and well-being into related but separate constructs prompted investigation into potential buffers to reduce the impact of mental illness on perceived well-being. This study explored two such buffers in health literacy and psychological resilience among Australian men. Using the Ten to Men Australian Longitudinal Study on Male Health, this secondary data analysis of n = 8,408 men between 18 and 60 years of age assessed the moderating effect of three components of health literacy (feeling supported by health care providers, ability to find health information, and active engagement with health care providers) and psychological resilience on the relationship between mental illness and well-being. Mental illness symptoms were negatively associated with well-being, whereas psychological resilience, active engagement with health care, and health care provider support (β res = .65, β eng = .28, and β sup = .25) had positive significant relationships with the outcome (all p ≤ .001). Ability to find health information ( p = .25) and psychological resilience ( p = .43) were not significantly associated with well-being. Of the four interactions tested, health literacy relating to health care worker support was the only significant moderator between mental illness and well-being (β sup = .03). This study identified that meaningful support and understanding from health care providers for Australian men aged between 18 and 60 years may somewhat ameliorate the impact of mental illness on well-being. Further related investigation may reveal specific interventions that improve perceptions of support among men., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: More Aboriginal and Torres Strait Islander young people experience high or very high levels of psychological distress compared to their non-Indigenous counterparts. This may be partly attributed to systemic barriers resulting in lower rates of help-seeking, sub-optimal identification of psychological challenges, and undertreatment. Reducing these barriers within health systems is an important factor in reducing the Social and Emotional Wellbeing (SEWB) health burden on young Aboriginal and Torres Strait Islander people., Objectives: In partnership with Miwatj Health Aboriginal Corporation (Miwatj), this project will co-design an integrated youth Social and Emotional Wellbeing (SEWB) and mental health stepped care model for remote Aboriginal communities in the north east Arnhem region of the Northern Territory., Design: A collaborative research approach using co-design methods will underpin a community-centric stepped care allocation method, to which culturally appropriate SEWB and mental health interventions and treatments are assigned. These components of the project will inform a digital platform which will facilitate access to SEWB care for young people in north east Arnhem land. This concept was co-developed in a partnership between researchers and Miwatj and builds on Miwatj's previous work to map the stepped needs of young people. The co-design of the content and features of these outputs will be facilitated through community participation and overseen by community, health, and cultural governance structures. This will ensure the solutions developed by the project are culturally responsive, fit for purpose, and will enhance self-determination while reducing systemic barriers to care., (© 2022 National Rural Health Alliance Ltd..)

Objective: In the Northern Territory, people who commit drink driving offences are required to undertake an approved course or treatment to be eligible for a driver's licence, however, course uptake is low. We investigated barriers to program uptake., Methods: We conducted semi-structured interviews with 24 program attendees, course providers and government stakeholders. We used a framework analysis., Results: Program coverage in remote areas was limited, leading to inequitable access. The course cost affected uptake and exacerbated existing financial hardship. There were mixed views among government stakeholders on the program. While some held a view that offenders should 'pay the price', some also saw the user-pays model and high program cost as a clear barrier to accessibility., Conclusions: The data from this study demonstrate how the current delivery model for drink and drug driving education increases inequities for those in regional and remote areas, and Aboriginal and Torres Strait Islander people., Implications for Public Health: Moving away from the current user-pays model to a subsidised or free model may facilitate greater access. Online delivery may increase accessibility; however, consultation is required to ensure the program is delivered equitably with consideration of language, literacy, cultural factors and access to technology., (© 2022 The Authors.)

Gunshot residue (GSR) stemming from the discharge of firearms has been essential to advancements in the field of forensic science however the human and environmental health impacts from GSR are far less researched. GSR represents a multifaceted concern: it contains a complex mixture of inorganic and organic components and produces airborne particles with variable sizes, depositions, and fates. Herein we evaluate studies in the literature examining GSR collection, deposition, composition, environmental contamination, and potential remediation techniques within the last two decades (2000 - 2020). Throughout we reflect upon key findings and weaknesses in relation to environmental characterization of GSR and associated firearm contaminants. Research focused on techniques to analyze both inorganic and organic GSR simultaneously has begun, but requires additional effort. A vast majority of the available environmental characterization literature focuses on soil contamination at outdoor firing ranges for a select number of elements (Cu, Pb, Sb) with comparisons between ranges or at different collection distances and depths. There is limited ability for between study comparisons due to collection and analysis differences as well as a lack of background soil sampling. Notably, these studies lack direct quantification of the contribution of contaminants from GSR as well as analysis of organic compounds. Currently, there is a need for air monitoring to determine the composition, deposition, and fate of GSR, particularly in outdoor settings. This review summarizes the collection, characterization, and environmental studies related to GSR and highlights areas of research needed to establish the environmental health impacts., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: In addition to providing injured workers with biomedical treatment, health care providers (HCPs) can promote return to work (RTW) through various communications., Objectives: To test the effect of several types of HCP communications on time loss following injury., Research Design: The authors analyzed survey and administrative claims data from a total of 730 injured workers in Victoria, Australia. Survey responses were collected around 5 months postinjury and provided data on HCP communication and confounders. Administrative claim records provided data on compensated time loss postsurvey. The authors conducted multivariate zero-inflated Poisson regressions to determine both the odds of having future time loss and its duration., Measures: Types of HCP communications included providing an estimated RTW date, discussing types of activities the injured worker could do or ways to prevent a recurrence, and contacting other RTW stakeholders. Each was measured in isolation as well as modified by a low-stress experience with the HCP. Time loss was the count of cumulative compensated work absence in weeks, accrued postsurvey., Results: RTW dates reduced the odds of future time loss [odds ratio, 0.26; 95% confidence interval (CI), 0.09-0.82] regardless of the stressfulness of the experience. Communications that predicted shorter durations of time loss only did so with low-stress experiences: RTW date [incidence rate ratio (IRR), 0.56; 95% CI, 0.50-0.63], stakeholder contact (IRR, 0.78; 95% CI, 0.70-0.87), and prevention discussions (IRR, 0.87; 95% CI, 0.78-0.98)., Conclusions: HCPs may reduce time loss through several types of communication, particularly when stress is minimized. RTW dates had the largest and most robust effect.

Purpose This study investigated the association between return to work self-efficacy (RTW-SE) and sustained return to work (RTW) at two different time points, over a 12-month period. The primary objective of the study was to examine if the relationship between RTW-SE and a sustained RTW changed over the RTW timeline. Methods This study used survey responses from a longitudinal cohort of n = 410 workers' compensation claimants with either an upper-body musculoskeletal injury or a psychological injury. A path analysis tested the associations between RTW-SE and a sustained RTW at two time-points. A Wald χ 2 test compared nested models to determine if the association changed over time. Results RTW-SE measured at time- point 1 (T1) was associated with a sustained RTW at time-point two (T2) (β = 0.24, P < 0.05) but no association was found between RTW-SE at T2 and a sustained RTW at time-point three (T3) (β = 0.017, n.s.). Model comparisons revealed significant differences in the associations between RTW-SE and a sustained RTW, with the relationship being stronger in the early phase of RTW compared to the latter phase (χ 2  = 5.002, p = 0.03). Conclusions The results indicate that RTW-SE at 4-6 months post-injury is important for a sustained RTW 6-months later although RTW-SE at 10-12 months post-injury had a negligible association over the same duration. Further research should investigate whether these findings generalize to other populations and what factors other than RTW-SE are associated with RTW in the later stages of the RTW process.

Background: Persistent pain and mental health conditions often co-occur after injury, cause enormous disability, reduce social and economic participation, and increase long-term healthcare costs. This study aimed to characterise the incidence, profile and healthcare cost implications for people who have a treated mental health condition, persistent pain, or both conditions, after compensable transport injury., Methods: The study comprised a population cohort of people who sustained a transport injury (n = 74,217) between 2008 to 2013 and had an accepted claim in the no-fault transport compensation system in Victoria, Australia. Data included demographic and injury characteristics, and payments for treatment and income replacement from the Compensation Research Database. Treated conditions were identified from 3 to 24-months postinjury using payment-based criteria developed with clinical and compensation system experts. Criteria included medications for pain, anxiety, depression or psychosis, and services from physiotherapists, psychologists, psychiatrists, and pain specialists. The data were analysed with Cox Proportional Hazards regression to examine rates of treated conditions, and general linear regression to estimate 24 month healthcare costs., Results: Overall, the incidence of treated mental health conditions (n = 2459, 3.3%) and persistent pain (n = 4708, 6.3%) was low, but rates were higher in those who were female, middle aged (35-64 years), living in metropolitan areas or neighbourhoods with high socioeconomic disadvantage, and for people who had a more severe injury. Healthcare costs totalled more than $A707 M, and people with one or both conditions (7.7%) had healthcare costs up to 7-fold higher (adjusting for demographic and injury characteristics) in the first 24 months postinjury than those with neither condition., Conclusions: The incidence of treated mental health and persistent pain conditions was low, but the total healthcare costs for people with treated conditions were markedly higher than for people without either treated condition. While linkage with other public records of treatment was not possible, the true incidence of treated conditions is likely to be even higher than that found in this study. The present findings can be used to prioritise the implementation of timely access to treatment to prevent or attenuate the severity of pain and mental health conditions after transport injury., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

We modified a popular and inexpensive quadcopter to collect gaseous mercury (Hg) on gold-coated quartz cartridges, and analyzed the traps using cold vapor atomic fluorescence spectrometry. Flight times averaged 16 min, limited by battery life, and yielded > 5 pg of Hg, well above the limit of detection (< 0.2 pg). We measured progressively higher concentrations upon both vertical and lateral approaches to a dish containing elemental Hg, demonstrating that the method can detect Hg emissions from a point source. Using the quadcopter, we measured atmospheric Hg near anthropogenic emission sources in the mid-south USA, including a municipal landfill, coal-fired power plant (CFPP), and a petroleum refinery. Average concentrations (± standard deviation) immediately downwind of the landfill were higher at ground level and 30 m compared to 60 and 120 m (5.3 ± 0.5 ng m -3 , 5.4 ± 0.7 ng m -3 , 4.2 ± 0.7 ng m -3 , and 2.5 ± 0.3 ng m -3 , respectively). Concentrations were also higher at an urban/industrial area (Memphis) (3.3 ± 0.9 ng m -3 ) compared with a rural/background area (1.5 ± 0.2 ng m -3 ). Due to airspace flight restrictions near the CFPP and refinery, we were unable to access near-field (stack) plumes and did not observe differences between upwind and downwind locations. Overall, this study demonstrates that highly maneuverable multicopters can be used to probe Hg concentrations aloft, which may be particularly useful for evaluating Hg emissions from remote landscapes and transient sources that are inadequately characterized and leading to uncertainties in ecosystem budgets.

Purpose Work absence can result in substantial losses to the economy and workers. As a result, identifying modifiable factors associated with return-to-work (RTW) following an injury or illness is the focus of many empirical investigations. Self-efficacy, the belief about one's ability to undertake behaviours to achieve desired goals, has been identified as an important factor in RTW for injured workers. This paper systematically reviewed the literature on the association between self-efficacy and RTW outcomes for workers with an upper-body musculoskeletal injury or psychological injury. Methods A systematic search was conducted across five databases using two main search concepts- 'self-efficacy' and 'RTW'. After removing duplicates, our search strategy identified 836 studies, which were screened for relevance using titles and abstracts. Results A two stage screening process reduced the study pool to six studies using psychological injury cohorts and three using upper-body musculoskeletal (UB-MSK) cohorts. Eight cohorts from seven prospective cohort studies and one sample from a randomised control trial (RCT) were subjected to a risk of bias assessment. Higher levels of self-efficacy appeared to have a consistent and positive association with RTW across return-to-work status and work absence outcomes, injury type and follow-up periods. Effect ratios ranged from 1.00 to 5.26 indicating a potentially large impact of self-efficacy on RTW outcomes. The relationship between self-efficacy and RTW strengthened as the domain of self-efficacy became more specific to RTW and job behaviours. Studies assessing workers with psychological injuries were of a lower quality compared to those assessing workers with UB-MSK injuries. Conclusions Higher self-efficacy had consistent positive associations with RTW outcomes. Further empirical research should identify the determinants of self-efficacy, and explore the processes by which higher self-efficacy improves RTW outcomes.

Humans throughout the world are exposed regularly to mixtures of environmental toxicants. Four of the most common heavy metal toxicants in the environment are mercury (Hg), cadmium (Cd), lead (Pb), and arsenic (As). Numerous studies have assessed the effects and disposition of individual metals in organ systems; however, humans are usually exposed to mixtures of toxicants or metals rather than to a single toxicant. Therefore, the purpose of the current study was to test the hypothesis that exposure to a mixture of toxic heavy metals alters the disposition of single metals in target organs. Wistar rats ( Rattus norvegicus ) were exposed to Hg, Cd, Pb, or As as a single metal or as a mixture of metals. Rats were injected intravenously for three days, following which kidneys, liver, brain, and blood were harvested. Samples were analyzed for content of Hg, Cd, Pb, and As via inductively coupled plasma mass spectrometry. In general, exposure to a mixture of metals reduced accumulation of single metals in target organs. Interestingly, exposure to mixtures of metals with Pb and/or As increased the concentration of these metals specifically in the liver. The findings from this study indicate that exposure to mixtures of toxic heavy metals may alter significantly the distribution and accumulation of these metals in target organs and tissues.

Objective: The objective of this study was to investigate modifiable early-injury factors which are associated with self-efficacy to return-to-work (RTW-SE) and explore whether these factors are different for people with psychological or upper-body musculoskeletal (UB-MSK) injuries., Methods: The study used a sample of workers with a UB-MSK (N = 244) or psychological (N = 113) injury who were off work. Differences between injury types were investigated across variables related to: (1) communication with RTW stakeholders; and (2) components of the job itself. A stratified and multigroup analysis was conducted using structural equation modeling (SEM)., Results: Injury-stratified models revealed no significant differences. In a combined model, higher job autonomy and low-stress contact from the RTW coordinator remained significantly associated with higher RTW-SE., Conclusions: Job autonomy and low-stress contact from the RTW coordinator are possible areas to target to increase self-efficacy among injured workers.

Children with sickle cell anemia (SCA) may be at risk of cerebral vasculopathy and strokes, which can be prevented by chronic transfusion programs. Repeated transfusions of packed red blood cells (PRBCs) is currently the simplest and most used technique for chronic transfusion programs. However, iron overload is one of the major side effects of this therapy. More developed methods exist, notably the apheresis of RBC (erythrapheresis), which is currently the safest and most efficient method. However, it is costly, complicated, and cannot be implemented everywhere, nor is it suitable for all patients. Manual exchange transfusions combine one or more manual phlebotomies with a PRBC transfusion. At the Reference Center of Sickle Cell Disease, we set up a continuous method of manual exchange transfusion that is feasible for all hospital settings, demands no specific equipment, and is widely applicable. In terms of HbS decrease, stroke prevention, and iron overload prevention, this method showed comparable efficiency to erythrapheresis. In cases where erythrapheresis is not available, this method can be a good alternative for patients and care centers.

Injuries at work have a substantial economic and societal burden. Often groups of labour market participants, such as young workers, recent immigrants or temporary workers are labelled as being "vulnerable" to work injury. However, defining groups in this way does little to enable a better understanding of the broader factors that place workers at increased risk of injury. In this paper we describe the development of a new measure of occupational health and safety (OH&S) vulnerability. The purpose of this measure was to allow the identification of workers at increased risk of injury, and to enable the monitoring and surveillance of OH&S vulnerability in the labour market. The development included a systematic literature search, and conducting focus groups with a variety of stakeholder groups, to generate a pool of potential items, followed by a series of steps to reduce these items to a more manageable pool. The final measure is 29-item instrument that captures information on four related, but distinct dimensions, thought to be associated with increased risk of injury. These dimensions are: hazard exposure; occupational health and safety policies and procedures; OH&S awareness; and empowerment to participate in injury prevention. In a large sample of employees in Ontario and British Columbia the final measure displayed minimal missing responses, reasonably good distributions across response categories, and strong factorial validity. This new measure of OH&S vulnerability can identify workers who are at risk of injury and provide information on the dimensions of work that may increase this risk. This measurement could be undertaken at one point in time to compare vulnerability across groups, or be undertaken at multiple time points to examine changes in dimensions of OH&S vulnerability, for example, in response to a primary prevention intervention., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To investigate occupational risk of musculoskeletal (MSK) and mental injury among ambulance officers and paramedics, and compare with nurse professionals, social and welfare professionals, and carers and aides in Victoria, Australia, using workers' compensation (WC) claims statistics., Methods: Data were retrieved from the Victorian Compensation Research Database (CRD). Analysis was restricted to claims received between 1 July 2003 and 30 June 2012. WC claim rates were calculated using labour force statistics, and expressed per 1000 full-time equivalent workers. Adjusted HRs with 95% CIs for injury risk were estimated using multivariable regression modelling., Results: Ambulance officers and paramedics had an upward trend in WC claim rates for all injuries and the highest rates for MSK and mental injury, in comparison with other healthcare workers during the study period. In the 2009-2012 time period, ambulance officers and paramedics' risk of lower back MSK and mental injury was approximately 13 times higher than nurse professionals, HRs 57.6 vs 4.4 and 17.77 vs 1.29, respectively. Social and welfare professionals had the second highest risk of mental injury, which was up to threefold greater than in nurses. Carers and aides and nurse professionals had similar HRs overall for all injury categories., Conclusions: Differential patterns of MSK and mental injury exist among healthcare occupational groups in Victoria, Australia. Given the significant findings, especially the high risks among ambulance personnel, future research should focus on the circumstances of injury to improve understanding and inform prevention programmes., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: To examine if the factors associated with days of absence following a work-related injury are similar for mental health versus musculoskeletal (MSK) conditions., Methods: A secondary analysis of wage replacement workers' compensation claims in the state of Victoria, Australia. We examined the relationship between individual, injury, occupational and workplace variables with days of wage replacement over the 2-year period following first day of absence from work separately for mental health claims and MSK claims using negative binomial regression models., Results: Mental health conditions were associated with a greater number of days of absence over the 2 years following first incapacity compared to MSK conditions. Differences were observed in employment, injury and industry variables on absence from work for mental claims compared to MSK claims. Working in the agriculture, forestry, fishing and mining industries and employment with a small organisation were more strongly associated with the number of days of wage-replacement among MSK compared to mental health claims, and working in the public administration and safety, or education and training industries or being employed in a position with high time pressure were associated with greater days of wage-replacement among mental health compared to MSK claims., Conclusions: Predictors of days away from work in the 2 years following an injury differ for mental health versus MSK claims. Given the increasing number of mental health claims in Australia more research is required to understand differences in return-to-work for this group of claimants compared to those with physical injuries.

Objective: To determine the prevalence, symptom characteristics, and potential risk factors for vestibular symptoms after cochlear implantation., Study Design: Case-control study design embedded within an ongoing cohort of patients undergoing implantation., Setting: Academic medical center cochlear implant research program funded by the National Institutes of Health., Patients: Seventy five eligible consecutive patients undergoing cochlear implantation., Intervention: Medical record review., Main Outcome Measure: Recorded symptoms of vestibular symptoms after cochlear implantation. Subjects with vestibular symptoms were considered case subjects; those without vestibular symptoms were considered control subjects., Results: Twenty-nine of 75 (39%) patients experienced dizziness postoperatively. Four patients experienced a single, transient acute vertigo attack occurring less than 24 hours after surgery. The majority, 25 patients, experienced delayed, episodic onset of vertigo. The median (interquartile range) time of delayed onset was 74 (26-377) days after implantation. Delayed dizziness manifested as spontaneous episodic or positional vertigo. Preoperative dizziness, age at implantation, and age at onset of hearing loss were significantly greater in the dizzy group. Preoperative electronystagmography did not differentiate between groups., Conclusions: Thirty-nine percent (29/75) of subjects with implants were dizzy after implantation. The majority of subjects experienced dizziness in a delayed episodic fashion. Dizziness was not related to implant activation. It seemed that delayed dizziness was not related to immediate surgical intervention but could result from chronic changes occurring in the inner ear; there was some suggestion this could take the form of endolymphatic hydrops.

In vitro and in vivo studies revealed that pancreases of Long-Evans male rats metabolized 3-methylcholanthrene (3MC) principally at the 1- and 2-carbon positions. The pancreatic metabolizing capability was not induced by pretreatment with either benzo(a)pyrene (BP) or phenobarbital (PB). During the period of observation from 5 to 48 hr, the maximum tissue content of radioactivity observed in the in vivo studies occurred at 16 hr after injection of 3MC in both liver and pancreas. Pancreatic tissue retained about four times more carcinogen per gram of tissue than liver tissues at all time periods.

Pancreases of Long-Evans rats were treated in vitro and in vivo with 3-methylcholanthrene and examined by histofluorescence techniques. For in vitro studies, tissue sections were dipped in 3-methylcholanthrene and incubated in vitro. These sections revealed that acinar and ductal epithelium had equal fluorescence which suggested equal metabolic capability. For in vivo experiments, 3-methylcholanthrene was injected intraperitoneally and the rats were killed 60 min later. Two additional rats were provided with biliary cannulae to divert bile from the pancreatobiliary ducts. Frozen sections, 16 mu in thickness, were prepared and examined under the fluorescence microscope. The sections revealed that fluorescence was concentrated in the epithelium and lumen of ducts. Animals with diversion of bile from the pancreatobiliary ducts had similar intensity and distribution of fluorescence. The in vivo studies showed that ductal epithelium was exposed to greater concentrations of carcinogen than nonductal epithelium. These observations provide a link between epidemiological studies that show an increased incidence of pancreatic adenocarcinoma in populations exposed to environmental carcinogens and morphological studies that show the ductal cell to be the most likely cell of origin.

A major problem in the therapy of pancreatic adenocarcinoma is its inherent resistance to most chemotherapeutic agents. Previously, we have reported that the four pancreatic cancer cell lines studied here have elevated levels of ornithine decarboxylase, a growth-regulating enzyme, and further that the degree of elevation tends to parallel the degree of chemoresistance. On the basis of these prior findings, we investigated the effects of alpha-difluoromethylornithine (DFMO), a specific inhibitor of ornithine decarboxylase, alone and in combination with cis-diamminedichloroplatinum(II) (cisplatin), to which two of the four cell lines display relative resistance. The cell lines studied were: two of human origin, PANC-1 and COLO-357; and two of hamster origin, WD PaCa and PD PaCa. Colony formation (clonogenic) assays were used to evaluate drug effects. Cells were exposed continuously to DFMO in medium. For the combined treatments, cells were exposed to cisplatin for 1 hr, washed, and then plated in DFMO-containing medium. The inhibitory effects of DFMO were predominantly cytostatic, were reversible by putrescine, and were roughly additive when combined with cisplatin. Our panel of cell lines responded heterogeneously to DFMO, with PANC-1 and WD PaCa showing the most sensitivity. The combination of DFMO and cisplatin appears to be a promising experimental approach to overcoming drug resistance in pancreatic cancer.

Implantation of 7,12-dimethylbenz(a)anthracene (DMBA) into the pancreas of rats has been shown to induce adenocarcinoma. Complexes of tubules, which have the appearance of proliferated intralobular ducts, frequently appear during tumor development. These complexes were studied by light and electron microscopy to determine their method of formation. In addition, a tubular complex was reconstructed from serial sections to determine its three-dimensional configuration. Although tubular complexes have been thought by others to result from ductal proliferation, the following observation indicate that they originate from zymogen-granule-containing cells: a) there is a continuum of transitional stages between acini and tubules, b) most tubules decrease in size and are replaced by connective tissue (evidence of regression rather than proliferation), c) few mitotic figures are seen in tubular complexes, d) the tubules comprise many cells which have an abundance of rough endoplasmic reticulum, an organelle which is sparce in ducts, and e) the three-dimensional arrangement of tubules appears identical to the branching, anastomosing arrangement of zymogen-granule-containing cells of the normal rat pancreas. Control animals in which only sutures were placed in the pancreas showed minimal reaction. It is concluded that "acini" become recognized as tubules when loss of zymogen granules accompanies tumor induction by DMBA. Transformation of these cells could be erroneously interpreted as transformation from proliferating ducts.

The present studies characterized the pancreatic metabolic system which biodegrades benzo[a]pyrene (BP), in male Sprague-Dawley rats pretreated with 20 mg/kg 3-methylcholanthrene (3MC), 75 mg/kg phenobarbital (PB) or solvent as control. Type of cytochrome involved was examined by measuring the reaction in the presence of 7,8-benzoflavone (BF), an inhibitor of the cytochrome P-448-related enzyme activity. The data indicated that the enzyme activity was induced by pretreatment with PB but not with 3MC. These pretreatment protocols resulted in changes both in Km and Vmax. Studies with BF suggested that pancreatic tissue may not contain more than one class of hemoprotein. These studies pointed out species differences between the rat and guinea pig, and confirmed the pancreatic capability to metabolize procarcinogens and to further degrade carcinogenic metabolites.

The in vitro metabolism of benzo(a)pyrene was compared between pancreas and liver with and without pretreatment. There was no significant difference in metabolic pathways between the two tissues. Evidence for induction of the metabolism was evident following 3-methyl-cholanthrene pretreatment. Temporal studies demonstrated rapid elimination of BP from the tissues within the first 5 hours with possible recirculation of metabolites 22 hours after injection of the carcinogen. There was significant binding of BP to DNA in pancreas and liver at 5 hours.

Because of the high incidence of pancreatic cancer in the United States and because of the correlation of pancreatic cancer to environmental exposure, we have undertaken experiments to measure the metabolism of the carcinogen 7,12-dimethylbenzanthracene in the pancreas of the Long-Evans male rat. This study examined the in vitro metabolism of the carcinogen and found the production of aqueous products in pancreas to be similar to that in liver, however, the pancreatic capability was not induced to greater metabolism by pretreatment with either phenobarbital or 3-methylcholanthrene. High pressure liquid chromatographic analysis of the in vitro products of pancreatic metabolism demonstrated a relatively greater abundance of 5,6-epoxy-7-hydroxymethyl-12-methylbenzanthracene than the liver and a relatively less abundance of 7-hydroxymethyl-12-methylbenzanthracene and 7-methyl-12-hydroxymethylbenzanthracene than the liver. Carcinogen levels were measured in pancreas, liver, bile and blood at 2, 5, 10, 16, 22 and 36 hours after injection.

This review outlines progress made during the past 11 years in research related to pancreatic acinar cell metabolism and function. We have reviewed information gained at the cellular level concerning structural and functional relationships, and effects of fasting and feeding, as well as the action of gastrointestinal hormones and cholinergic agonists on acinar cells. In toto, this information outlines a significant role for gastrointestinal hormones as mediators of secretion, synthesis, and control of trophism. This information provides a basis for more sophisticated inquiries as to the mechanisms of injury of alcohol and drugs. The information may prove helpful in developing diagnostic modalities for pancreatic disease, as well as understanding the processes involved in neoplastic transformation.