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Insertion of the laryngeal mask airway (LMA) without muscle relaxant requires adequate obtundation of airway reflexes, which may otherwise lead to incorrect or failed LMA placement. This study compared topical lignocaine spray vs. intravenous (IV) fentanyl, during propofol induction for insertion of the ProSeal™ LMA (PLMA). This was a prospective, randomized, double blind study, in ASA I or II patients, for elective or emergency surgery. Seventy patients ( n = 70) who fulfilled the inclusion criteria were randomly assigned to receive IV fentanyl 2 mcg/kg or topical lignocaine spray 40 mg, prior to anesthesia induction with IV propofol (2-2.5 mg/kg). ProSeal™ LMA insertion condition was regarded optimal in the absence of adverse responses (gag, cough, laryngospasm and body movements), and successful LMA placement at the first attempt. Hemodynamic parameters were recorded and patients were assessed for sore throat and hoarseness post operatively. Seventy patients were analyzed. The number of patients with optimal PLMA insertion conditions were comparable between the groups (60% vs. 57%, P = 0.808). All hemodynamic parameters were comparable between groups with the exception of heart rate. Sympathetic obtundation of heart rate was greater with IV fentanyl than topical lignocaine ( P < 0.05). The proportion of patients with postoperative sore throat significantly increased with the number of insertion attempts ( P < 0.05). Topical lignocaine spray to the pharynx is as effective, and may be an alternative to IV fentanyl, during propofol induction for PLMA insertion. Success rate and optimal insertion condition at the first attempt, propofol requirement, blood pressure, adverse events and airway complications were comparable. Heart rate obtundation was less with topical lignocaine spray but remained within clinically acceptable values., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Rahmat Ameen Noorazyze, Nor, Zain, Mohamad Yusof and Yong.)

Purpose: Excision of wrist ganglions is a common procedure in hand surgery. Our objective was to determine whether the type of anesthesia (general anesthesia [GA] vs wide-awake local anesthesia no tourniquet [WALANT] technique) would affect patient satisfaction regarding intraoperative pain control, postoperative pain management, and anxiety., Methods: This was a prospective study with patients divided into either the WALANT or GA cohort. The waiting time for surgery, Amsterdam Preoperative Anxiety and Information Scale, blood pressure, and heart rate were measured. Postsurgical questionnaires with the visual analog scale were completed. The surgeon's feedback on the ease of ganglion stalk visibility and usage of diathermy as a measure of a bloodless field was recorded. Patients reported the amount of analgesia consumed and overall satisfaction with the operation via the Surgical Satisfaction-8 questionnaire., Results: A total of 42 patients underwent wrist ganglion excision in 2 orthopedic centers over a period of 2 years, with 21 undergoing GA and 22 undergoing WALANT. The GA group was more anxious about anesthetic use with a higher demand for information about GA ( P  = .04). The duration of surgery was significantly shorter in the WALANT group and with a lower diathermy usage ( P < .001). There was no difference in terms of surgical difficulty and stalk visualization. The visual analog scale pain score was significantly lower in the WALANT group than in the GA group immediately after surgery ( P  = .04) and on discharge ( P  = .004). While at home for 2 weeks, the WALANT group (mean = 2.91 tablets) consumed significantly fewer analgesic tablets than the GA group (mean = 6.25 tablets). However, both groups were satisfied with their experience., Conclusions: Wide-awake local anesthesia no tourniquet technique in the excision of ganglions provides another option of anesthesia with painless experiences, and no pain rebound after surgery. Patients were less anxious about WALANT than GA. Excision can be performed without diathermy usage with similar visualization of the stalk., Type of Study/level of Evidence: Therapeutic II., (© 2022 The Authors.)

Objectives: This study investigates the use of tibia-mounted inertial measurement units (IMUs) as an alternative to upper trunk-mounted IMUs for assessing lower limb training magnitudes and asymmetries in Badminton players., Design: Cross-Sectional Study., Setting: Youth athlete training environment., Participants: Thirty-three adolescent Badminton players, grouped based on injury history (non-injured = 19, bilateral = 6, unilateral = 8)., Main Outcome Measures: Players wore 1 upper trunk-mounted and 2 tibia-mounted IMUs during simulated match-play. Modified vector magnitudes were assessed to identify if the IMUs can discriminate between injury history groups to assess the device location sensitivity, determine to what extent players exhibit movement asymmetry within the sport, and explore if asymmetries exist within groups with injury history., Results: Upper trunk-mounted IMUs could not distinguish between injury history groups. Statistically significant asymmetries were observed in the non-injured group, however these were below the 10% threshold for clinical asymmetry. No significant asymmetries were observed in the bilaterally injured group, while statistically significant asymmetries were observed in the unilaterally injured group, which were above the 10% threshold for clinical asymmetry., Conclusion: These results suggest that direct limb specific IMU measurement offers a method to suitably assess training magnitudes and asymmetry within a sporting performance, rather than isolated non-sport specific testing., Competing Interests: Declaration of competing interest None declared., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Psoriasis is a chronic skin disease characterized by thickening and disorganization of the skin's protective barrier. Although current models replicate some aspects of the disease, development of therapeutic strategies have been hindered by absence of more relevant models. This study aimed to develop and characterize an in vitro psoriatic human skin equivalent (HSE) using human keratinocytes HaCat cell line grown on fibroblasts-derived matrices (FDM). The constructed HSEs were treated with cytokines (IL-1α, TNF-α, IL-6, and IL22) to allow controlled induction of psoriasis-associated features. Histological stainings showed that FDMHSE composed of a fully differentiated epidermis and fibroblast-populated dermis comparable to native skin and rat tail collagen-HSE. Hyperproliferation (CK16 and Ki67) and inflammatory markers (TNF-α and IL-6) expression were significantly enhanced in the cytokine-induced FDM- and rat tail collagen HSEs compared to non-treated HSE counterparts. The characteristics were in line with those observed in psoriasis punch biopsies. Treatment with all-trans retinoic acid (ATRA) has shown to suppress these effects, where HSE models treated with both ATRA and cytokines exhibit histological characteristics, hyperproliferation and differentiation markers expression like non-treated control HSEs. Cytokine-induced FDM-HSE, constructed entirely from human cell lines, provides an excellent opportunity for psoriasis research and testing new therapeutics.

Background: Nut consumption at the population level remains low despite the well-documented benefits of their consumption, including their cardioprotective effects. Studies have suggested that advice from health professionals may be a means to increase nut consumption levels. Understanding how nuts are perceived by the public and health professionals, along with understanding the public's perceptions of motivators of and deterrents to consuming nuts, may inform the development of initiatives to improve on these low levels of consumption. The aim of this cross-sectional study was to compare perceptions of nuts among three groups of health professionals (dietitians, general practioners, and practice nurses) and the general public in New Zealand (NZ), along with motivators of and deterrents to consuming nuts amongst the general public and their experiences of receiving advice around nut consumption., Methods: The NZ electoral roll was used to identify dietitians, general practitioners (GPs), and practice nurses, based on their free-text occupation descriptions, who were then invited to complete a questionnaire with 318, 292, and 149 respondents respectively. 1,600 members of the general public were randomly selected from the roll with 710 respondents. Analyses were performed using chi-squared tests to look at differences in categorical variables and linear regression for differences in other variables between the four survey groups., Results: Although there were significant differences between the four groups regarding the perceptions of nuts, in general there was agreement that nuts are healthy, high in protein and fat, are filling, and some nuts are high in selenium. We noted frequent agreement that the general public participants would consume more if nuts: improved health (67%), were more affordable (60%), or improved the nutrient content (59%) and balance of fats (58%) within their diets. Over half the respondents reported they would eat more nuts if they were advised to do so by a dietitian or doctor, despite less than 4% reporting they had received such advice. The most frequently selected deterrents to increasing nut consumption were: cost (67%), potential weight gain (66%), and leading to eating too much fat (63%)., Discussion: It is concerning that so few among the general public report receiving advice to consume more nuts from health professionals, especially given their apparent responsiveness to such advice. Health professionals could exploit the motivators of nut consumption, while also addressing the deterrents, to promote nut intake. These factors should also be addressed in public health messages to encourage regular nut consumption among the public. Educational initiatives could also be used to improve the nutritional knowledge of GPs and practice nurses with regard to nuts, although even dietitians were unsure of their knowledge in some cases., Competing Interests: Andrew Robert Gray is an Academic Editor for PeerJ.

Background: Chromosome translocations are a biomarker of cumulative exposure to ionizing radiation. We examined the relation between the frequency of translocations and cosmic radiation dose in 83 male airline pilots., Methods: Translocations were scored using fluorescence in situ hybridization chromosome painting. Cumulative radiation doses were estimated from individual flight records. Excess rate and log-linear Poisson regression models were evaluated., Results: Pilots' estimated median cumulative absorbed dose was 15 mGy (range 4.5-38). No association was observed between translocation frequency and absorbed dose from all types of flying [rate ratio (RR) = 1.01 at 1 mGy, 95% confidence interval (CI) 0.97-1.04]. However, additional analyses of pilots' dose from only commercial flying suggested an association (RR = 1.04 at 1 mGy, 95% CI 0.97-1.13)., Discussion: Although this is the largest cytogenetic study of male commercial airline pilots to date of which the authors are aware, future studies will need additional highly exposed pilots to better assess the translocation-cosmic radiation relation.Grajewski B, Yong LC, Bertke SJ, Bhatti P, Little MP, Ramsey MJ, Tucker JD, Ward EM, Whelan EA, Sigurdson AJ, Waters MA. Chromosome translocations and cosmic radiation dose in male U.S. commercial airline pilots. Aerosp Med Hum Perform. 2018; 89(7):616-625.

Objective: Despite evidence linking regular nut consumption with reduced chronic disease risk, population-level intakes remain low. Research suggests nut-promoting advice from doctors facilitates regular nut consumption. However, there is no information on current nut recommendation practices of health professionals. The aim of the present study was to examine the advice provided by health professionals regarding nut consumption., Design: In this cross-sectional study, participants were invited to complete a survey including questions about their nut recommendation practices., Setting: New Zealand (NZ)., Subjects: The NZ Electoral Roll was used to identify dietitians, general practitioners and practice nurses., Results: In total 318 dietitians, 292 general practitioners and 149 practice nurses responded. Dietitians were more likely (82·7 %) to recommend patients increase consumption of nuts than general practitioners (55·5 %) and practice nurses (63·1 %; both P<0·001). The most popular nuts recommended were almonds, Brazil nuts and walnuts, with most health professionals recommending raw nuts. The most common recommendation for frequency of consumption by dietitians and practice nurses was to eat nuts every day, while general practitioners most frequently recommended 2-4 times weekly, although not statistically significantly different between professions. Dietitians recommended a significantly greater amount of nuts (median 30 g/d) than both general practitioners and practice nurses (20 g/d; both P<0·001)., Conclusions: Dietitians were most likely to recommend consumption of nuts in accordance with current guidelines, but there are opportunities to improve the adoption of nut consumption recommendations for all professions. This may be a viable strategy for increasing population-level nut intakes to reduce chronic disease.

Objective: Despite considerable evidence supporting the health benefits of regular nut consumption, nut intakes remain lower than recommended among many populations. Understanding how the general population perceives nuts could inform strategies to promote regular nut consumption and increase intakes among the general public., Design: Cross-sectional study. Participants were invited to complete a questionnaire which included information on nut consumption and knowledge and perceptions of nuts., Setting: The study was set in New Zealand (NZ)., Subjects: Participants (n 1600), aged 18 years or over, were randomly selected from the NZ electoral roll., Results: A total of 710 participants completed the questionnaire (response rate 44 %). More than half of the respondents believed that nuts are healthy, filling, high in protein and high in fat. The most common reason cited by consumers for eating nuts was taste (86 % for nuts, 85 % for nut butters), while dental issues was the most frequent reason for avoidance. About 40 % of respondents were not aware of the effects of nut consumption on lowering blood cholesterol and CVD risk., Conclusions: Despite overall basic knowledge of the nutritional value of nuts, a substantial proportion of the general population was unaware of the cardioprotective effects of nuts. The present study identified common motivations for eating and avoiding nuts, as well as perceptions of nuts which could affect intake. These should guide the content and direction of public health messages to increase regular nut consumption. The public's knowledge gaps should also be addressed.

Despite their nutritional value, population-level nut consumption remains low. Studies suggest that individuals would eat more nuts on their doctor's advice, making health professionals potentially important for promoting nut consumption. This cross-sectional study aimed to examine the perceptions and knowledge of nuts and the predictors of nut promotion among health professionals in New Zealand. Dietitians, general practitioners (GPs), and practice nurses were identified from the Electoral Roll and invited to complete a questionnaire (n = 318, 292, and 149 respondents respectively). Over one-fifth of GPs and practice nurses believed that eating nuts could increase blood cholesterol concentrations and cause weight gain. The most common perceptions overall were that nuts are healthy; high in protein, fat, and calories; and are satiating. Nut consumption was recommended for reasons relating to these perceptions and because of nuts' selenium content. Conversely, reasons for suggesting the consumption of fewer nuts included that they were high in calories and fat, would cause weight gain, and concerns regarding allergies and cost. All groups of health professionals were more likely to promote nut consumption if they perceived nuts to reduce the risk of diabetes (all p ≤ 0.034). Education could improve health professionals' knowledge regarding the effects of nut consumption on blood cholesterol and body weight, alongside other health benefits, which should improve the advice given to patients and may thereby increase nut consumption.

Objective: To estimate the prevalence of a comprehensive set of self-reported sleep problems by job characteristics, including shiftwork status, among a representative sample of US workers., Methods: Data for 6338 workers aged ≥18 years were obtained from the National Health and Nutrition Examination Survey. Short sleep duration was defined as <7 hours per weekday/workday. Sleep quality was categorised as good, moderate and poor based on the frequency of 6 sleep-related symptoms. A sleep-related activities of daily living (ADL) score ≥2 was defined as impaired. Insomnia was defined as having poor sleep quality and impaired ADL. Shiftwork status was categorised as daytime, night, evening, rotating or another schedule. Prevalence rates were calculated and multivariate logistic regression analyses were used., Results: The prevalence of short sleep duration (37.6% overall) was highest among night shift workers (61.8%; p<0.001). The prevalence of poor sleep quality was 19.2% among all workers, with the highest prevalence among night shift workers (30.7%, p=0.004). The prevalence of impaired ADL score (24.8% overall) and insomnia (8.8% overall) was also highest for night shift workers (36.2%, p=0.001 and 18.5%, p=0.013, respectively). In multivariate analysis, night shift workers had the highest likelihood of these sleep problems., Conclusions: Self-reported short sleep duration, poor sleep quality, impaired ADL score and insomnia are common among US workers especially among night shift workers. Although these findings should be confirmed with objective sleep measures, they support the need for intervention programmes to improve sleep quantity and quality among night shift workers., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background and Objective: This was a prospective, randomized clinical study to compare the success rate of nasogastric tube insertion by using GlideScope™ visualization versus direct MacIntosh laryngoscope assistance in anesthetized and intubated patients., Methods: Ninety-six ASA I or II patients, aged 18-70 years were recruited and randomized into two groups using either technique. The time taken from insertion of the nasogastric tube from the nostril until the calculated length of tube had been inserted was recorded. The success rate of nasogastric tube insertion was evaluated in terms of successful insertion in the first attempt. Complications associated with the insertion techniques were recorded., Results: The results showed success rates of 74.5% in the GlideScope™ Group as compared to 58.3% in the MacIntosh Group (p=0.10). For the failed attempts, the nasogastric tube was successfully inserted in all cases using rescue techniques. The duration taken in the first attempt for both techniques was not statistically significant; Group A was 17.2±9.3s as compared to Group B, with a duration of 18.9±13.0s (p=0.57). A total of 33 patients developed complications during insertion of the nasogastric tube, 39.4% in Group A and 60.6% in Group B (p=0.15). The most common complications, which occurred, were coiling, followed by bleeding and kinking., Conclusion: This study showed that using the GlideScope™ to facilitate nasogastric tube insertion was comparable to the use of the MacIntosh laryngoscope in terms of successful rate of insertion and complications., (Copyright © 2015 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.)

Background: We evaluated mortality among 5,964 former U.S. commercial cockpit crew (pilots and flight engineers). The outcomes of a priori interest were non-chronic lymphocytic leukemia, central nervous system (CNS) cancer (including brain), and malignant melanoma., Methods: Vital status was ascertained through 2008. Life table and Cox regression analyses were conducted. Cumulative exposure to cosmic radiation was estimated from work history data., Results: Compared to the U.S. general population, mortality from all causes, all cancer, and cardiovascular diseases was decreased, but mortality from aircraft accidents was highly elevated. Mortality was elevated for malignant melanoma but not for non-chronic lymphocytic leukemia. CNS cancer mortality increased with an increase in cumulative radiation dose., Conclusions: Cockpit crew had a low all-cause, all-cancer, and cardiovascular disease mortality but elevated aircraft accident mortality. Further studies are needed to clarify the risk of CNS and other radiation-associated cancers in relation to cosmic radiation and other workplace exposures., (© 2014 Wiley Periodicals, Inc.)

Objectives: To determine the prevalence of cigarette smoking cessation and examine the association between cessation and various factors among workers in a nationally representative sample of US adults., Methods: Data were derived from the 2010 National Health Interview Survey. Prevalence rates were calculated for interest in quitting smoking, making an attempt to quit smoking, and successful smoking cessation (defined as smokers who had quit for 6-12 months). Logistic regression analyses were used to identify factors associated with cessation after adjustment for demographic characteristics (age group, race/ethnicity, educational level and marital status)., Results: Data were available for 17 524 adults who were employed in the 12 months prior to interview. The prevalence of quit interest, quit attempt and recent cessation was 65.2%, 53.8% and 6.8%, respectively. Quit interest was less likely among workers with long work hours, but more likely among workers with job insecurity, or frequent workplace skin and/or respiratory exposures. Quit attempt was more likely among workers with a hostile work environment but less likely among workers living in a home that permitted smoking or who smoked ≥11 cigarettes/day. Recent smoking cessation was less likely among workers with frequent exposure to others smoking at work or living in a home that permitted smoking, but more likely among workers with health insurance., Conclusions: Factors associated with cessation interest or attempt differed from those associated with successful cessation. Cessation success might be improved by reducing exposure to others smoking at work and home, and by improving access to health insurance.

Objectives: US commercial airline pilots, like all flight crew, are at increased risk for specific cancers, but the relation of these outcomes to specific air cabin exposures is unclear. Flight time or block (airborne plus taxi) time often substitutes for assessment of exposure to cosmic radiation. Our objectives were to develop methods to estimate exposures to cosmic radiation and circadian disruption for a study of chromosome aberrations in pilots and to describe workplace exposures for these pilots., Methods: Exposures were estimated for cosmic ionizing radiation and circadian disruption between August 1963 and March 2003 for 83 male pilots from a major US airline. Estimates were based on 523 387 individual flight segments in company records and pilot logbooks as well as summary records of hours flown from other sources. Exposure was estimated by calculation or imputation for all but 0.02% of the individual flight segments' block time. Exposures were estimated from questionnaire data for a comparison group of 51 male university faculty., Results: Pilots flew a median of 7126 flight segments and 14 959 block hours for 27.8 years. In the final study year, a hypothetical pilot incurred an estimated median effective dose of 1.92 mSv (absorbed dose, 0.85 mGy) from cosmic radiation and crossed 362 time zones. This study pilot was possibly exposed to a moderate or large solar particle event a median of 6 times or once every 3.7 years of work. Work at the study airline and military flying were the two highest sources of pilot exposure for all metrics. An index of work during the standard sleep interval (SSI travel) also suggested potential chronic sleep disturbance in some pilots. For study airline flights, median segment radiation doses, time zones crossed, and SSI travel increased markedly from the 1990s to 2003 (P(trend) < 0.0001). Dose metrics were moderately correlated with records-based duration metrics (Spearman's r = 0.61-0.69)., Conclusions: The methods developed provided an exposure profile of this group of US airline pilots, many of whom have been exposed to increasing cosmic radiation and circadian disruption from the 1990s through 2003. This assessment is likely to decrease exposure misclassification in health studies.

Experimental studies suggest that B vitamins such as niacin, folate, riboflavin, vitamin B6 and vitamin B12 may protect against DNA damage induced by ionising radiation (IR). However, to date, data from IR-exposed human populations are not available. We examined the intakes of these B vitamins and their food sources in relation to the frequency of chromosome translocations as a biomarker of cumulative DNA damage, in eighty-two male airline pilots. Dietary intakes were estimated by using a self-administered semi-quantitative FFQ. Translocations in peripheral blood lymphocytes were scored by using fluorescence in situ hybridisation whole-chromosome painting. Negative binomial regression was used to estimate rate ratios and 95 % CI, adjusted for age and occupational and lifestyle factors. We observed a significant inverse association between translocation frequency and dietary intake of niacin (P = 0·02): adjusted rate ratio for subjects in the highest tertile compared with the lowest tertile was 0·58 (95 % CI 0·40, 0·83). Translocation frequency was not associated with total niacin intake from food and supplements as well as dietary or total intake of folate, riboflavin or vitamin B6 or B12. However, the adjusted rate ratios were significant for subjects with ≥ median compared with < median intake of whole grains (P = 0·03) and red and processed meat (P = 0·01): 0·69 (95 % CI 0·50, 0·96) and 1·56 (95 % CI 1·13, 2·16), respectively. Our data suggest that a high intake of niacin from food or a diet high in whole grains but low in red and processed meat may protect against cumulative DNA damage in IR-exposed persons.

Controversy regarding potential health risks from increased use of medical diagnostic radiologic examinations has come to public attention. We evaluated whether chromosome damage, specifically translocations, which are a potentially intermediate biomarker for cancer risk, was increased after exposure to diagnostic X-rays, with particular interest in the ionizing radiation dose-response below the level of approximately 50 mGy. Chromosome translocation frequency data from three separately conducted occupational studies of ionizing radiation were pooled together. Studies 1 and 2 included 79 and 150 medical radiologic technologists, respectively, and study 3 included 83 airline pilots and 50 university faculty members (total = 155 women and 207 men; mean age = 62 years, range 34-90). Information on personal history of radiographic examinations was collected from a detailed questionnaire. We computed a cumulative red bone marrow (RBM) dose score based on the numbers and types of X-ray examinations reported with 1 unit approximating 1 mGy. Poisson regression analyses were adjusted for age and laboratory method. Mean RBM dose scores were 49, 42, and 11 for Studies 1-3, respectively (overall mean = 33.5, range 0-303). Translocation frequencies significantly increased with increasing dose score (P < 0.001). Restricting the analysis to the lowest dose scores of under 50 did not materially change these results. We conclude that chromosome damage is associated with low levels of radiation exposure from diagnostic X-ray examinations, including dose scores of approximately 50 and lower, suggesting the possibility of long-term adverse health effects.

Background: Dietary antioxidants may protect against DNA damage induced by endogenous and exogenous sources, including ionizing radiation (IR), but data from IR-exposed human populations are limited., Objective: The objective was to examine the association between the frequency of chromosome translocations, as a biomarker of cumulative DNA damage, and intakes of vitamins C and E and carotenoids in 82 male airline pilots., Design: Dietary intakes were estimated by using a self-administered semiquantitative food-frequency questionnaire. Translocations were scored by using fluorescence in situ hybridization with whole chromosome paints. Negative binomial regression was used to estimate rate ratios and 95% CIs, adjusted for potential confounders., Results: Significant and inverse associations were observed between translocation frequency and intakes of vitamin C, beta-carotene, beta-cryptoxanthin, and lutein-zeaxanthin from food (P < 0.05). Translocation frequency was not associated with the intake of vitamin E, alpha-carotene, or lycopene from food; total vitamin C or E from food and supplements; or vitamin C or E or multivitamin supplements. The adjusted rate ratios (95% CI) for > or =median compared with or =median compared with

Background: Despite the endocrine system activity exhibited by polychlorinated biphenyls (PCBs), recent studies have shown little association between PCB exposure and breast cancer mortality., Objectives: To further evaluate the relation between PCB exposure and breast cancer risk, we studied incidence, a more sensitive end point than mortality, in an occupational cohort., Methods: We followed 5,752 women employed for at least 1 year in one of three capacitor manufacturing facilities, identifying cases from questionnaires, cancer registries, and death certificates through 1998. We collected lifestyle and reproductive information via questionnaire from participants or next of kin and used semiquantitative job-exposure matrices for inhalation and dermal exposures combined. We generated standardized incidence ratios (SIRs) and standardized rate ratios and used Cox proportional hazards regression models to evaluate potential confounders and effect modifiers., Results: Overall, the breast cancer SIR was 0.81 (95% confidence interval, 0.72-0.92; n = 257), and regression modeling showed little effect of employment duration or cumulative exposure. However, for the 362 women of questionnaire-identified races other than white, we observed positive, statistically significant associations with employment duration and cumulative exposure; only smoking, birth cohort, and self- or proxy questionnaire completion had statistically significant explanatory power when added to models with exposure metrics., Conclusions: We found no overall elevation in breast cancer risk after occupational exposure to PCBs. However, the exposure-related risk elevations seen among nonwhite workers, although of limited interpretability given the small number of cases, warrant further investigation, because the usual reproductive risk factors accounted for little of the increased risk.

Background: Chromosome translocations are an established biomarker of cumulative exposure to external ionising radiation. Airline pilots are exposed to cosmic ionising radiation, but few flight crew studies have examined translocations in relation to flight experience., Methods: We determined the frequency of translocations in the peripheral blood lymphocytes of 83 airline pilots and 50 comparison subjects (mean age 47 and 46 years, respectively). Translocations were scored in an average of 1039 cell equivalents (CE) per subject using fluorescence in situ hybridisation (FISH) whole chromosome painting and expressed per 100 CE. Negative binomial regression models were used to assess the relationship between translocation frequency and exposure status and flight years, adjusting for age, diagnostic x ray procedures, and military flying., Results: There was no significant difference in the adjusted mean translocation frequency of pilots and comparison subjects (0.37 (SE 0.04) vs 0.38 (SE 0.06) translocations/100 CE, respectively). However, among pilots, the adjusted translocation frequency was significantly associated with flight years (p = 0.01) with rate ratios of 1.06 (95% CI 1.01 to 1.11) and 1.81 (95% CI 1.16 to 2.82) for a 1- and 10-year incremental increase in flight years, respectively. The adjusted rate ratio for pilots in the highest compared to the lowest quartile of flight years was 2.59 (95% CI 1.26 to 5.33)., Conclusions: Our data suggests that pilots with long-term flying experience may be exposed to biologically significant doses of ionising radiation. Epidemiological studies with longer follow-up of larger cohorts of pilots with a wide range of radiation exposure levels are needed to clarify the relationship between cosmic radiation exposure and cancer risk.

The U.S. population has nearly one radiographic examination per person per year, and concern about cancer risks associated with medical radiation has increased. Radiologic technologists were surveyed to determine whether their personal cumulative exposure to diagnostic X-rays was associated with increased frequencies of chromosome translocations, an established radiation biomarker and possible intermediary suggesting increased cancer risk. Within a large cohort of U.S. radiologic technologists, 150 provided a blood sample for whole chromosome painting and were interviewed about past X-ray examinations. The number and types of examinations reported were converted to a red bone marrow (RBM) dose score with units that approximated 1 mGy. The relationship between dose score and chromosome translocation frequency was assessed using Poisson regression. The estimated mean cumulative RBM radiation dose score was 49 (range, 0-303). After adjustment for age, translocation frequencies significantly increased with increasing RBM dose score with an estimate of 0.004 translocations per 100 cell equivalents per score unit (95% confidence interval, 0.002-0.007; P < 0.001). Removing extreme values or adjustment for gender, cigarette smoking, occupational radiation dose, allowing practice X-rays while training, work with radioisotopes, and radiotherapy for benign conditions did not affect the estimate. Cumulative radiation exposure from routine X-ray examinations was associated independently with increased chromosome damage, suggesting the possibility of elevated long-term health risks, including cancer. The slope estimate was consistent with expectation based on cytogenetic experience and atomic bomb survivor data.

Chromosome translocations in peripheral blood lymphocytes of normal, healthy humans increase with age, but the effects of gender, race, and cigarette smoking on background translocation yields have not been examined systematically. Further, the shape of the relationship between age and translocation frequency (TF) has not been definitively determined. We collected existing data from 16 laboratories in North America, Europe, and Asia on TFs measured in peripheral blood lymphocytes by fluorescence in situ hybridization whole chromosome painting among 1933 individuals. In Poisson regression models, age, ranging from newborns (cord blood) to 85 years, was strongly associated with TF and this relationship showed significant upward curvature at older ages versus a linear relationship (p<0.001). Ever smokers had significantly higher TFs than non-smokers (rate ratio (RR)=1.19, 95% confidence interval (CI), 1.09-1.30) and smoking modified the effect of age on TFs with a steeper age-related increase among ever smokers compared to non-smokers (p<0.001). TFs did not differ by gender. Interpreting an independent effect of race was difficult owing to laboratory variation. Our study is three times larger than any pooled effort to date, confirming a suspected curvilinear relationship of TF with age. The significant effect of cigarette smoking has not been observed with previous pooled studies of TF in humans. Our data provide stable estimates of background TF by age, gender, race, and smoking status and suggest an acceleration of chromosome damage above age 60 and among those with a history of smoking cigarettes.

Measurement of chromosome translocations in peripheral blood lymphocytes has been used to quantify prior exposure to ionizing radiation, including for workers exposed to low, chronic doses. We assessed translocation frequencies in a subset of U.S. radiologic technologists to substantiate ionizing radiation dose estimates developed for 110,418 technologists who worked between 1916 and 1984. From 3,441 cohort members known to have begun working before 1950, we selected a sample of 152, stratified by estimated cumulative dose, over-sampling from higher-dose categories and excluding persons with a prior cancer diagnosis, a personal or family history of chromosomal instability disorders, or a current history of smoking. Estimates of film-badge dose ranged from less than 10 cSv to more than 30 cSv. Blood samples, obtained in 2004, were analyzed by fluorescence in situ hybridization (FISH) whole chromosome painting by simultaneously labeling chromosomes 1, 2 and 4 in red and 3, 5 and 6 in green. Translocations were scored in 1800 well-spread metaphase cells and expressed per 100 cell equivalents (CE) per person. Linear Poisson regression models with allowance for overdispersion were used to assess the relationship between estimated occupational red bone marrow absorbed dose in cGy and translocation frequency, adjusted for age, gender and estimated red bone marrow absorbed dose score from personal diagnostic procedures. We observed 0.09 excess translocations per 100 CE per cGy red bone marrow dose (95% CI: -0.01, 0.2; P = 0.07), which is similar to the expected estimate based on previous cytogenetic studies (0.05 excess translocations per 100 CE per cGy). Despite uncertainty in the estimates of occupational red bone marrow absorbed doses, we found good general agreement between the doses and translocation frequencies, lending support to the credibility of the dose assessment for this large cohort of U.S. radiologic technologists.

Background: Ethylene oxide (EtO), an important industrial chemical intermediate and sterilant, is classified as a human carcinogen. Occupational EtO exposure in many countries is regulated at 1 ppm (8-hr TWA), but levels of EtO-DNA adducts in humans with low occupational EtO exposures have not been reported., Methods: We examined the formation of N7-(2'-hydroxyethyl)guanine (N7-HEG), a major DNA adduct of EtO, in 58 EtO-exposed sterilizer operators and six nonexposed workers from ten hospitals. N7-HEG was quantified in granulocyte DNA (0.1-11.5 microg) by a highly sensitive and specific gas chromatography-electron capture-mass spectrometry method. Cumulative exposure to EtO (ppm-hour) was estimated during the 4-month period before the collection of blood samples., Results: There was considerable inter-individual variability in the levels of N7-HEG with a range of 1.6-241.3 adducts/10(7) nucleotides. The mean levels in the nonexposed, low (< or =32 ppm-hour), and high (>32 ppm-hour) EtO-exposure groups were 3.8, 16.3, and 20.3 adducts/10(7) nucleotides, respectively, after the adjustment for cigarette smoking and other potential confounders, but the differences were not statistically significant., Conclusions: This study has demonstrated for the first time, detectable levels of N7-HEG adducts in granulocytes of hospital workers with EtO exposures at levels less than the current U.S. standard of 1 ppm (8-hr TWA). A nonsignificant increase in adduct levels with increasing EtO exposure indicates that further studies of EtO-exposed workers are needed to clarify the relationship between EtO exposure and N7-HEG adduct formation.

Purpose: Lung cancer is a leading cause of cancer death worldwide. Although smoking remains the predominant cause of lung cancer, lung cancer in never smokers is an increasingly prominent public health issue. However, data on this topic, particularly lung cancer incidence rates in never smokers, are limited., Methods: We reviewed the existing literature on lung cancer incidence and mortality rates among never smokers and present new data regarding rates in never smokers from the following large, prospective cohorts: Nurses' Health Study; Health Professionals Follow-Up Study; California Teachers Study; Multiethnic Cohort Study; Swedish Lung Cancer Register in the Uppsala/Orebro region; and First National Health and Nutrition Examination Survey Epidemiologic Follow-Up Study., Results: Truncated age-adjusted incidence rates of lung cancer among never smokers age 40 to 79 years in these six cohorts ranged from 14.4 to 20.8 per 100,000 person-years in women and 4.8 to 13.7 per 100,000 person-years in men, supporting earlier observations that women are more likely than men to have non-smoking-associated lung cancer. The distinct biology of lung cancer in never smokers is apparent in differential responses to epidermal growth factor receptor inhibitors and an increased prevalence of adenocarcinoma histology in never smokers., Conclusion: Lung cancer in never smokers is an important public health issue, and further exploration of its incidence patterns, etiology, and biology is needed.

Nutrient concentration and hydrocarbon bioavailability are key factors affecting biodegradation rates of oil in contaminated beach sediments. The effect of a slow-release fertilizer, Osmocote, as well as two biopolymers, chitin and chitosan, on the bioremediation of oil-spiked beach sediments was investigated using an open irrigation system over a 56-day period under laboratory conditions. Osmocote was effective in sustaining a high level of nutrients in leached sediments, as well as elevated levels of microbial activity and rates of hydrocarbon biodegradation. Chitin was more biodegradable than chitosan and gradually released nitrogen into the sediment. The addition of chitin or chitosan to the Osmocote amended sediments enhanced biodegradation rates of the alkanes relative to the presence of Osmocote alone, where chitosan was more effective than chitin due to its greater oil sorption capacity. Furthermore, chitosan significantly enhanced the biodegradation rates of all target polycyclic aromatic hydrocarbons.

Fluidization finds many process applications in the areas of catalytic reactions, drying, coating, combustion, gasification and microbial culturing. This work aims to compare the dynamic adsorption characteristics and adsorption rates in a bubbling fluidized bed and a fixed bed at the same gas flow-rate, gas residence time and bed height. Adsorption with 520 ppm methanol and 489 ppm isobutane by the ZSM-5 zeolite of different particle size in the two beds enabled the differentiation of the adsorption characteristics and rates due to bed type, intraparticle mass transfer and adsorbate-adsorbent interaction. Adsorption of isobutane by the more commonly used activated carbon provided the comparison of adsorption between the two adsorbent types. With the same gas residence time of 0.79 seconds in both the bubbling bed and fixed bed of the same bed size of 40 mm diameter and 48 mm height, the experimental results showed a higher rate of adsorption in the bubbling bed as compared to the fixed bed. Intraparticle mass transfer and adsorbent-adsorbate interaction played significant roles in affecting the rate of adsorption, with intraparticle mass transfer being more dominant. The bubbling bed was observed to have a steeper decline in adsorption rate with respect to increasing outlet concentration compared to the fixed bed. The adsorption capacities of zeolite for the adsorbates studied were comparatively similar in both beds; fluidizing, and using smaller particles in the bubbling bed did not increase the adsorption capacity of the ZSM-5 zeolite. The adsorption capacity of activated carbon for isobutane was much higher than the ZSM-5 zeolite for isobutane, although at a lower adsorption rate. Fourier transform infra-red (FTIR) spectroscopy was used as an analytical tool for the quantification of gas concentration. Calibration was done using a series of standards prepared by in situ dilution with nitrogen gas, based on the ideal gas law and relating partial pressure to gas concentration. Concentrations up to 220 ppm for methanol and 75 ppm for isobutane were prepared using this method.

Ethylene oxide (EtO) is a genotoxic carcinogen with widespread uses as an industrial chemical intermediate and sterilant. We examined the effects of glutathione S-transferase T1 (GSTT1) and M1 (GSTM1) genotypes on the levels of N-(2-hydroxyethyl)valine (HEV) adducts in the erythrocytes and sister chromatid exchange (SCE) in lymphocytes from a group of 58 operators of sterilizers that used EtO and nonexposed workers from nine hospitals in the United States and one hospital in Mexico City. Cumulative exposure to EtO was estimated during the 4-month period before the collection of blood samples. Results showed that EtO exposure was significantly associated with the levels of HEV adducts and SCE after adjusting for cigarette smoking and other potential confounders. A significantly higher HEV adduct level (0.17 +/- 0.03 versus 0.08 +/- 0.01, mean +/- SE; P = 0.02) but lower SCE frequency (5.31 +/- 0.39 versus 6.21 +/- 0.17; P = 0.04) was observed in subjects with homozygous deletion of the GSTT1 gene (null genotype) as compared with those with at least one copy of the gene (positive genotype). In multiple regression analysis, the GSTT1-null genotype was associated with an increase in HEV adduct level (beta = 1.62; P = 0.02) and a decrease in SCE frequency (beta = -1.25; P = 0.003) after adjusting for age, gender, race, education, cigarette smoking, and EtO exposure status. The inverse SCE-GSTT1 relationship remained unchanged when SCE was further examined in relation to HEV adducts as an indicator of the internal EtO dose. The GSTM1 genotype was not associated with the level of either HEV adduct or SCE. These data indicate that the GSTT1-null genotype is associated with increased formation of EtO-hemoglobin adducts in relation to occupational EtO exposure, suggesting that individuals with homozygous deletion of the GSTT1 gene may be more susceptible to the genotoxic effects of ETO: The unexpected finding of decreased SCEs, which is less clear, may be attributed to the nonchemical specificity of this end point and the lack of expression of the GSTT1 enzyme in lymphocytes.

The mast cell remains an enigmatic cell more than 100 years after its discovery by Paul Ehrlich at the turn of the century. It is a cell that is found widely distributed in the body particularly associated with connective tissues. It can be recognised by its content of metachromatic granules when appropriately fixed and stained with metachromatic dyes such as toulidine blue. The metachromatic granules of the mast cell remain an important differentiating characteristic from other cells although it is by no means absolute. In the early days of its discovery it was thought to originate from primitive mesenchyme, thymocyte or lymphocyte. More recent evidence suggests that it may have originated from the monocyte. Current evidence points to an origin from haemopoietic tissue in the bone marrow, the progenitors differentiate from primitive cells under the influence of cytokines (IL3), migrate to other body sites and then undergo differentiation and maturation under the influence of growth and other factors. The mast cell has many functions exerted through its ability to produce a host of biologically active substances the most notable being heparin, serotonin, dopamine, tryptase and chymase. These substances may be released in response to immunological and neural stimuli. Mast cells are found to be functionally heterogeneous, possibly site specific and have the ability to adapt to their environment, producing secretions commensurate with the needs of any situation. The mast cell is involved in immunological, neoplastic, inflammatory and other conditions. Much about its function has been unravelled but there remains more to be uncovered.

The relation between the dietary intake of vitamins E, C, and A (estimated by a 24-hour recall) and lung cancer incidence was examined in the First National Health and Nutrition Examination Survey Epidemiologic Followup Study cohort of 3,968 men and 6,100 women, aged 25-74 years. During a median follow-up period of 19 years (from 1971-1975 to 1992), 248 persons developed lung cancer. Adjusted for potential confounders using Cox proportional hazards regression methods with age as the underlying time variable, the relative risk of lung cancer for subjects in the highest quartile of vitamin C intake compared with those in the lowest quartile was 0.66 (95% confidence interval (CI) 0.45-0.96). For vitamin A intake, a protective effect was observed only for its fruit and vegetable component (carotenoids) among current smokers (relative risk = 0.49, 95% CI 0.29-0.84), but this was modified by the intensity of smoking (a statistically significant effect (relative risk = 0.33, 95% CI 0.13-0.84) was observed only for those in the lowest tertile of pack-years of smoking). The vitamin E intake-lung cancer relation was modified by the intensity of smoking with a significant protective effect confined to current smokers in the lowest tertile of pack-years of smoking (relative risk = 0.36, 95% CI 0.16-0.83). Overall, there was no additional protective effect of supplements of vitamins E, C, and A beyond that provided through dietary intake. When vitamin E, vitamin C, and carotenoid intakes were examined in combination, a strong protective effect was observed for those in the highest compared with those in the lowest quartile of all three intakes (relative risk = 0.32, 95% CI 0.14-0.74). These data provide support for a protective role of dietary vitamins E and C and of carotenoids against lung cancer risk but with a modification in effects by the intensity of cigarette exposure. While smoking avoidance is the most important behavior to reduce lung cancer risk, the daily consumption of a variety of fruits and vegetables that provides a combination of these nutrients and other potential protective factors may offer the best dietary protection against lung cancer.

Despite extensive research on obesity and breast cancer in recent decades, inconsistencies in the literature exist. The authors examined prospectively the relation between adult relative weight (weight (kg)/height (m)1.5) and breast cancer risk in a cohort of 54,896 women aged 31-89 years who had previously participated in the Breast Cancer Detection Demonstration Project. During a mean follow-up period of 7 years, 226 of the premenopausal women and 1,198 of the postmenopausal women developed breast cancer. Analysis was performed using Cox proportional hazards regression methods with age as the underlying time variable and adjusted for the effects of potential confounders. Among postmenopausal women, the risk of breast cancer increased with increasing relative weight (p < 0.05 for trend); relative risk for the highest compared with the lowest quintile for relative weight was 1.3 (95% confidence interval (CI) 1.1-1.6). This association was modified by age at diagnosis, with relative risks of 1.1 (95% CI 0.8-1.4), 1.2 (95% CI 0.8-1.7), and 1.8 (95% CI 1.3-2.5), respectively, for women aged < 60, 60-64, and > or = 65 years. The higher risk of breast cancer among the older and overweight women was largely confined to women whose weights were measured during the postmenopausal but not the premenopausal period. This risk pattern was observed among the naturally menopausal women, but was also apparent in the smaller group of women with bilateral oophorectomy or hysterectomy with one ovary retained. Among premenopausal women, adult relative weight was not associated with breast cancer risk. These findings suggest that the inconsistencies in the literature on obesity and breast cancer may be due in part to the differing age distributions of the populations studied. The authors conclude that prevention of obesity throughout adulthood, particularly after menopause, may help reduce breast cancer among older women.

The development of risk factors for young adults to older ages for women has been evaluated in several studies. The increase in risk factor levels is related to age, weight gain, and diet. The levels of risk factors are related to extent of atherosclerosis, even at relatively young ages. The prevention of increase in risk factors is of primary importance for the future reduction of morbidity and mortality due to cardiovascular disease.

Notexin, a well known neurotoxin, derived from tiger snake venom, was shown to have direct nephrotoxic properties in experimental mice. A single subcutaneous dose of 1.38 micrograms/kg body weight of notexin produced renal tubular and glomerular damage within 24 hours. Renal damage increased in severity proportional to the dose of notexin injected. At a high dose of notexin, thrombotic "spherules" were found in glomeruli. These thrombotic spherules have not been previously reported to be associated with notexin or snake venoms.

Methods: Tracking of blood pressure was studied in a cohort of 86 men and 116 women, initially examined at mean age 17 years and re-examined at mean ages 34 and 47 years in the Dormont High School Follow-up Study., Results: Correlations for systolic blood pressure (men vs women, P < 0.05) were r = 0.42 vs r = 0.39 between mean ages 17 and 34 years; r = 0.38 vs r = 0.54 between mean ages 34 and 47 years; and r = 0.27 vs r = 0.24 between mean ages 17 and 47 years. For diastolic blood pressure, the correlations were lower, but were higher among women than men, and were higher between mean ages 34 and 47 years (r = 0.44 for men and r = 0.54 for women, P < 0.001) than at earlier ages. The correlations for weight were higher than those for blood pressure (men vs women, P < 0.001): r = 0.64 vs r = 0.59 between mean ages 17 and 34 years; r = 0.88 vs r = 0.81 between mean ages 34 and 47 years; and r = 0.58 vs r = 0.49 between mean ages 17 and 47 years. With increase in age and length of follow-up, there was a stronger tendency for those in the extreme tertiles of the blood pressure distribution to maintain their ranks. The significance and magnitude of the blood pressure correlations remained essentially unchanged after adjustment for weight and its changes. However, weight was related to the changes in blood pressure tracking status, but this varied with age., Conclusion: These data suggest that the age and gender differences in the degree of blood pressure tracking may be a function of the tracking of weight as well as a reflection of the gender difference in the consistency of the relationship of blood pressure to weight at different ages.

The changes and determinants of blood pressure were examined in the Dormont High School (Pittsburgh, Pennsylvania) cohort of 86 men and 116 women with mean ages of 17 years during high school (1957-1963), 34 years at follow-up I (1977-1978), and 47 years at current follow-up II (1989-1990). Over the 30-year period, the subjects' mean systolic blood pressure changed relatively little, whereas the increase in mean diastolic blood pressure was significantly higher in men than in women (p < 0.01). Based on the criteria of diastolic blood pressure > or = 90 mmHg, and/or current use of antihypertensive medication, 18% developed hypertension. Compared with nonhypertensives, hypertensives had significantly higher baseline systolic blood pressure (p < 0.001); higher weight at all ages (p < 0.05); and gained more weight over the period (p < 0.01). By means of multivariate analyses, it was found that baseline systolic blood pressure, current weight, and weight gain were significantly and independently associated with current systolic blood pressure level and hypertension. These data indicate that initial systolic blood pressure level at adolescence, current weight, and weight gain are important determinants of risk of high blood pressure, and there is a further suggestion of sex and age differences in the critical period of risk.

Aipysurus laevis venom has been shown to have a direct nephrotoxic effect in mice. A single subcutaneous injection (0.075 mg/kg body wt.) of the whole venom caused acute renal tubular degeneration and proliferative glomerulonephritis. The tubular changes appeared within 1 hour and remained for at least 14 days. Mesangial proliferative glomerulonephritis developed within 3-10 days, and is characterised by mild mesangial proliferation, mesangial and glomerular basement membrane deposits. This is followed by a partial resolution and subsequent mesangial sclerosis. The exact pathogenesis of venom-induced glomerulonephritis is not clear although it may have an immunological basis similar to that seen in human poststreptococcal glomerulonephritis. It was not possible to clarify the nature of the deposits by conventional immunohistochemical stains.

There is comparatively little knowledge of the structure and function of cultured lymphatic endothelium. A study was carried out to compare the intrinsic growth characteristics of cultured lymphatic endothelial cells with cultured endothelial derived from blood vessels. It was found that cultured lymphatic endothelium has growth requirements and growth characteristics similar to vascular endothelium. It also possesses FVIIIRA and Weibel-Palade bodies for specific identification. The results of this study have provided important base line data for subsequent studies of the pathobiology of lymphatic endothelium.

A study of the clearance of anti GBM antibodies is important for an understanding of the pathogenesis of Goodpasture's syndrome. This paper reports a study of the sequential clearance of heterologous anti-glomerular basement membrane antibodies in the neonatal rat. A single intraperitoneal injection was followed by rapid and linear binding of injected antibodies to glomerular basement membranes, particularly to those glomeruli in the corticomedullary region. GBM bound antibodies were cleared gradually through the mesangium and significant amounts of antibodies still remained bound after 6 months. Subsequent injections of antibodies failed to provoke morphological abnormalities. These experiments have shown that the glomerular basement membrane of neonatal and adult rats possesses similar antigenic sites. The mesangium plays a major role in the clearance of injected heterologous antibodies. The slow clearance of antibodies from the GBM indicates a strong affinity of antibodies to antigenic sites and that the removal of antibodies is intimately related to the slow metabolic turnover of the glomerular basement membrane. The findings help to explain some of the observations in human antibasement membrane antibody mediated disease of the Goodpasture's type.

Lymphatic endothelial cells isolated from bovine mesenteric lymphatic vessels were cultured and characterized. Lymphatic endothelial cells grew as a monolayer displaying an elongated morphology in preconfluent primary cultures. When confluent, the cells exhibited a polygonal morphology to form a "cobblestone" pattern previously described for cultured vascular endothelium. All culture lymphatic endothelial cells expressed Factor VIII-related antigen and bound Ulex europaeus I lectin. Ultrastructurally, cultured lymphatic endothelium was characterized by the presence of Weibel-Palade bodies as well as the usual cytoplasmic organelles.

Adult Wistar rats were subjected to a chemical carcinogenesis regimen involving initiation with diethylnitrosamine (DEN) and cytotoxic selection of initiated cells following partial hepatectomy. The livers of treated rats exhibited sequential changes of vacuolar degeneration and hepatocellular nodular hyperplasia up to 5 mth after completion of the experimental regimen. The hyperplastic nodules regressed slowly at that time. Cystic bile duct hyperplasia emerged with high frequency between 5 and 15 mth after completion of the regimen. The nitrosamine-initiated nodular and biliary hyperplasias could not be unequivocally accepted as preneoplastic lesions since frankly neoplastic transformation under these conditions was a relatively rare occurrence.

The immunological and structural changes during the heterologous phase of experimental antibasement membrane antibody mediated disease was sequentially studied in the rat following single i.v. injections of rabbit antibodies to basement membrane antigens prepared from kidney, lung and salivary gland tissues. Although each of the anti-bodies bound strongly to GBM, structural changes were initially subtle accompanied by proteinuria and hematuria. More severe structural changes related to dose and duration of the disease did not appear for several weeks.

Adult Wistar rats rendered diabetic by a single dose of streptozotocin develop renal morphological changes which show subtle differences compared to those seen in human diabetic renal disease. The early tubular degeneration is sited in the distal rather than the proximal convoluted tubule and subsequent glomerular lesion shows linear deposits of IgG and albumin in the basement membrane rather than in the mesangium. The carcinogenicity of streptozotocin in the rat is reconfirmed.

The changing population-density of mast cells in various organs was plotted for rats aged 1/2 to 90 days and correlated with histochemical studies on the stage of maturation of cells. Mast cells are present at birth in liver and spleen and are particularly associated with foci of haemopoiesis. In bone marrow mast cells are absent at birth but become progressively more numerous with increasing age of the animal. The association of mast cells firstly with foci of extramedullary haemopoiesis and secondly with medullary foci coupled with their detection in peripheral blood strongly suggests that mastopoiesis may be analogous with granulopoiesis. In thymus mast cells are usually associated with interlobular connective tissue stroma, but in the parenchyma they are found toward the medullary side of the cortico-medullary junction. Such a distribution suggests the possible origin of mast cells from lymphocyte or thymocyte. In other tissues examined mast cells are frequently associated with connective tissue stroma and blood vessels.

It has been suspected that pulmonary lesions of the Goodpasture type may be the result of circulating antibodies to alveolar basement membrane and that environmental factors such as cigarette smoke may influence antibody binding. Carefully designed experiments in this study have shown that exposure to cigarette smoke for 3 weeks or 100% oxygen for 65 h did not influence the binding of heterologous antibodies to alveolar basement membrane in Wistar rats, nor did these regimes increase any pathological changes associated with the antibody binding as detected by light microscopy. The results which are at variance with other reported findings are discussed with reference to reported animal models of antibody mediated pneumonitis and Goodpasture's syndrome in man.

A 5-year-old girl suffered Campylobacter jejuni enteritis. Over the ensuing weeks she developed glomerulonephritis, pulmonary hemorrhage and anemia. Renal biopsy revealed immune-complex mediated, crescentic glomerulonephritis. Campylobacter jejuni antigen was identified in the glomeruli suggesting a causal role of Campylobacter jejuni in the disease process.