Biochar effect on sheep feed intake, growth rate and ruminant in vitro and in vivo methane production.

Biochar, which is the product of biomass pyrolysis, has been suggested as a feed supplement to improve performance in livestock systems and reduce greenhouse gas emissions. The aim of the current study was to investigate in vitro and in vivo potential of biochar to favourably modify rumen fermentation (e.g., an increase in total Short Chained Fatty Acid (SCFA) concentration and a change in SCFA profile), reduce methane emission and increase sheep growth performance. Four concentrates were produced with biochar inclusion of 0, 10, 23 and 46 g/kg DM. The experimental diets for the in vitro experiments consisted of straw and concentrate in a 60:40 ratio and included measurements of total gas and methane (CH4) production, pH, ammonia nitrogen, SCFA, and microbial assays (total bacteria and methanogenic archaea). Two in vivo experiments were performed where the animals received ad libitum forage with 0.4 kg concentrate daily. Experiment 1 investigated the daily DM intake of sheep while experiment 2 investigated daily growth rate and CH4 emission of lambs. The inclusion of biochar had no impact on in vitro total gas production (ml/200 mg DM substrate) (P = 0.81) and CH4 production (ml/200 mg DM substrate) (P = 0.93). In vitro total SCFA concentration increased (P < 0.05) while acetate to propionate ratio (A:P) tended to decrease (P = 0.05) with both doses of biochar. Total bacteria decreased with the highest biochar inclusion in vitro (P < 0.05). Sheep's DM intake (kg/d) increased when low and medium levels but not when a higher level of biochar was added to the diet (P < 0.001). The inclusion of biochar did not significantly impact the lamb's daily growth rate (g/d) (P = 0.61) or enteric CH4 emissions (g/kg DM) (P = 0.43). We conclude that biochar supplementation had no favourable impacts on in vitro and in vivo CH4 production or on lamb's growth rate. Further research with well-characterised biochar is needed to gain a better understanding of the potential of biochar as a feed additive for ruminant livestock.

Patients' perspectives on point-of-care diagnostics and treatment by emergency medical technicians in acute COPD exacerbations: A qualitative study.

BACKGROUND: In Denmark emergency medical technicians transport patients with acute COPD exacerbations to the nearest emergency department. From a clinical and economic perspective, this transport and assessment at the hospital may be inconvenient if the patient is immediately discharged from the emergency department. We established an emergency technical technicians point-of-care diagnostics and treatment program of patients with COPD with use of ultrasound and blood analysis. Patients' perspectives on treatment at home and sense of security are important to qualify clinical practice at home with patients with acute exacerbation. AIM AND OBJECTIVES: To explore patient's and relatives' experience of treatment at home during emergency calls due to COPD in exacerbation and to investigate their attitude to avoid hospitalization as well as experience of stress during point-of-care diagnostics in their own home. METHOD: A qualitative study comprising semi-structured interviews with 16 patients carried out from April 1st, 2019 to March 31st, 2020 in Denmark. Data was analysed inspired by Malteruds' text condensation and informed by Critical Psychology with first person perspective focusing on the patient's views on point-of-care diagnostics and treatment of their COPD in acute exacerbation. RESULTS: The interviews revealed that in order to ensure an experience of quality in the assessment and treatment of patients in their own homes, it was important that the ambulance staff showed great safety and experience in the use of the technical equipment and treatment of dyspnea. It was also of importance that the patients felt confident that their general practitioner followed up on the home treatment initiated. CONCLUSION: Patients' perspectives showed that point-of-care diagnostics and treatment of acute COPD in exacerbation was considered a qualitative offer by the patients and their relatives. At the same time, it was crucial that the emergency medical technicians showed experience and safety in handling shortness of breath as well as the technical equipment. TRIAL REGISTRATION: Approved by the Danish Data Protection Agency Project-ID: 20/24845.

Organ-based tube current modulation in chest CT. A comparison of three vendors.

INTRODUCTION: Organ-based tube current modulation (OBTCM) is designed for anterior dose reduction in Computed Tomography (CT). The purpose was to assess dose reduction capability in chest CT using three organ dose modulation systems at different kVp settings. Furthermore, noise, diagnostic image quality and tumour detection was assessed. METHODS: A Lungman phantom was scanned with and without OBTCM at 80-135/140 kVp using three CT scanners; Canon Aquillion Prime, GE Revolution CT and Siemens Somatom Flash. Thermo-luminescent dosimeters were attached to the phantom surface and all scans were repeated five times. Image noise was measured in three ROIs at the level of the carina. Three observers visually scored the images using a fivestep scale. A Wilcoxon Signed-Rank test was used for statistical analysis of differences. RESULTS: Using the GE revolution CT scanner, dose reductions between 1.10 mSv (12%) and 1.56 mSv (24%) (p < 0.01) were found in the anterior segment and no differences posteriorly and laterally. Total dose reductions between 0.64 (8%) and 0.91 mSv (13%) were found across kVp levels (p < 0.00001). Maximum noise increase with OBTCM was 0.8 HU. With the Canon system, anterior dose reductions of 6-10% and total dose reduction of 0.74-0.76 mSv across kVp levels (p < 0.001) were found with a maximum noise increase of 1.1 HU. For the Siemens system, dose increased by 22-51% anteriorly; except at 100 kVp where no dose difference was found. Noise decreased by 1 to 1.5 HU. CONCLUSION: Organ based tube current modulation is capable of anterior and total dose reduction with minimal loss of image quality in vendors that do not increase posterior dose. IMPLICATIONS FOR PRACTICE: This research highlights the importance of being familiar with dose reduction technologies.

The validity of nasal endoscopy in patients with chronic rhinosinusitis-An inter-rater agreement study.

OBJECTIVES: Nasal endoscopy is a cornerstone in diagnosing sinonasal disease, but different raters might generate different results using the technique. Our study aims to evaluate the agreement between multiple raters to assess the validity of nasal endoscopy. DESIGN/PARTICIPANTS: Three independent and blinded raters evaluated 28 patients (56 nasal cavities) diagnosed with chronic rhinosinusitis according to the European Position Paper on Rhinosinusitis and Nasal Polyps. The ratings were compared using unweighted Fleiss' kappa coefficients (Kf ) for each objective parameter. SETTING: The department of Otorhinolaryngology, Odense University Hospital, Denmark. MAIN OUTCOME MEASURES: The ratings were quantified in a modified Lund-Kennedy endoscopy score and focused on the objective parameters specified in the diagnostic criteria: polyps, oedema and discharge. RESULTS: The raters agreed on the findings concerning polyps and discharge but not regarding oedema with the inter-rater agreement for the different parameters being: polyps Kf =.66 (SE .07, P<.001), oedema Kf =.05 (SE .07, P=.21), discharge Kf =.35 (SE .08, P<.001), oedema exclusively in middle meatus Kf =-.07 (SE .04, P=.8) and discharge exclusively in middle meatus Kf =.16 (SE .07, P=.01). CONCLUSION: Using nasal endoscopy, the evaluation of polyps by multiple raters showed sufficient reliability indicating an acceptable objective evaluation. The evaluation of discharge achieved a fair level of agreement while the assessment of oedema could not achieve a sufficient reliability questioning the inclusion of oedema in the criteria for diagnosing sinonasal disease.

Editor's Choice - The National Norwegian Carotid Study: Time from Symptom Onset to Surgery is too Long, Resulting in Additional Neurological Events.

OBJECTIVE/BACKGROUND: The objective was to observe for 1 year all patients in Norway operated on for symptomatic carotid stenosis with respect to (i) the time from the index event to surgery and neurological events during this time; (ii) the level in the healthcare system causing delay of surgical treatment; and (iii) the possible relationship between peri-operative use of platelet inhibitors and neurological events while awaiting surgery. METHODS: This was a prospective national multicentre study of a consecutive series of symptomatic patients. Patients were eligible for inclusion when referred for surgery. An index event was defined as the neurological event prompting contact with the healthcare system. All 15 departments in Norway performing carotid endarterectomy (CEA) participated. RESULTS: Three hundred and seventy one patients were eligible for inclusion between 1 April 2014 and 31 March 2015, and 368 patients (99.2%) were included. Fifty-four percent of the patients contacted their general practitioner on the day of the index event. Primary healthcare referred 84.2% of the patients to hospital on the same day as examined. In hospital median time from admission to referral for vascular surgery was 3 days. Median time between referral to the operating unit and actual CEA was 5 days. Overall, 61.7% of the patients were operated on within 2 weeks of the index event. Twelve patients (3.3%) suffered a new neurological event while awaiting surgery. The percentage of patients on dual antiplatelet therapy was lower (25.0%) in this group than among the other patients (62.6%) (p = .008). The combined 30 day mortality and stroke rate was 3.8%. CONCLUSION: This national study with almost complete inclusion and follow-up shows that the delays occur mainly at patient level and in hospital. The delay is associated with new neurological events. Dual antiplatelet therapy is associated with reduced risk of having a new neurological event before surgery.

Management of horses with focus on blanketing and clipping practices reported by members of the Swedish and Norwegian equestrian community.

Limited information is available on the extent to which blankets are used on horses and the owners' reasoning behind clipping the horse's coat. Research on the effects of those practices on horse welfare is scarce but results indicate that blanketing and clipping may not be necessary from the horse's perspective and can interfere with the horse's thermoregulatory capacities. Therefore, this survey collected robust, quantitative data on the housing routines and management of horses with focus on blanketing and clipping practices as reported by members of the Swedish and Norwegian equestrian community. Horse owners were approached via an online survey, which was distributed to equestrian organizations and social media. Data from 4,122 Swedish and 2,075 Norwegian respondents were collected, of which 91 and 84% of respondents, respectively, reported using blankets on horses during turnout. Almost all respondents owning warmblood riding horses used blankets outdoors (97% in Sweden and 96% in Norway) whereas owners with Icelandic horses and coldblood riding horses used blankets significantly less ( < 0.05). Blankets were mainly used during rainy, cold, or windy weather conditions and in ambient temperatures of 10°C and below. The horse's coat was clipped by 67% of respondents in Sweden and 35% of Norwegian respondents whereby owners with warmblood horses and horses primarily used for dressage and competition reported clipping the coat most frequently. In contrast to scientific results indicating that recovery time after exercise increases with blankets and that clipped horses have a greater heat loss capacity, only around 50% of respondents agreed to these statements. This indicates that evidence-based information on all aspects of blanketing and clipping has not yet been widely distributed in practice. More research is encouraged, specifically looking at the effect of blankets on sweaty horses being turned out after intense physical exercise and the effect of blankets on social interactions such as mutual grooming. Future efforts should be tailored to disseminate knowledge more efficiently, which can ultimately stimulate thoughtful decision-making by horse owners concerning the use of blankets and clipping the horse's coat.

Changes in knee joint load indices from before to 12 months after arthroscopic partial meniscectomy: a prospective cohort study.

OBJECTIVE: Patients undergoing arthroscopic partial meniscectomy (APM) are at increased risk of knee osteoarthritis (OA). Meniscal damage and/or surgery may alter knee joint loading to increase OA risk. We investigated changes in knee joint loading following medial APM surgery, compared with the contra-lateral leg. METHODS: We estimated indices of knee joint loading (external peak knee adduction moment (KAM), KAM impulse and peak knee flexion moment (KFM)) normalized to body size (i.e., body mass (BM) and height (HT)) using 3D gait analysis in 23 patients (17 men, mean (SD) 46.2 (6.4) years, BMI 25.8 (3.4) kg/m(2)) without radiographic knee OA before and 12 months after medial APM. Static alignment was assessed by radiography and self-reported outcomes by Knee injury and Osteoarthritis Outcome Score (KOOS). RESULTS: Peak KAM and KAM impulse increased in the APM leg compared to the contra-lateral leg from before to 12 months after surgery (change difference: 0.38 Nm/BM*HT% 95% CI 0.01 to 0.76 (P = 0.049) and 0.20 Nm*s/BM*HT% 95% CI 0.10 to 0.30 (P < 0.001)). Patients self-reported improvements on all KOOS subscales (KOOS pain improvement: 22.8 95% CI 14.5 to 31.0 (P < 0.01)). CONCLUSIONS: A relative increase in indices of medial compartment loading was observed in the leg undergoing APM compared with the contra-lateral leg from before to 12 months after surgery. This increase may contribute to the elevated risk of knee OA in these patients. Randomized trials including a non-surgical control group are needed to determine if changes in joint loading following APM are caused by surgery or by changes in symptoms.

Preference for shelter and additional heat in horses exposed to Nordic winter conditions.

REASONS FOR PERFORMING STUDY: Horses may adapt to a wide range of temperatures and weather conditions. Owners often interfere with this natural thermoregulation ability by clipping and use of blankets. OBJECTIVES: To investigate the effects of different winter weather conditions on shelter seeking behaviour of horses and their preference for additional heat. STUDY DESIGN: Observational study in various environments. METHODS: Mature horses (n = 22) were given a free choice test between staying outdoors, going into a heated shelter compartment or into a nonheated shelter compartment. Horse location and behaviour was scored using instantaneous sampling every minute for 1 h. Each horse was tested once per day and weather factors were continuously recorded by a local weather station. RESULTS: The weather conditions influenced time spent outdoors, ranging from 52% (of all observations) on days with mild temperatures, wind and rain to 88% on days with <0°C and dry weather. Shivering was only observed during mild temperatures and rain/sleet. Small Warmblood horses were observed to select outdoors less (34% of all observations) than small Coldblood horses (80%). We found significant correlations between hair coat sample weight and number of observations outdoors (ρ = 0.23; P = 0.004). CONCLUSIONS: Horses selected shelters the most on days with precipitation and horses changed from a nonheated compartment to a heated compartment as weather changed from calm and dry to wet and windy. Horse breed category affected the use of shelter and body condition score and hair coat weight were associated with voluntary shelter selection.

A Nordic survey of management practices and owners' attitudes towards keeping horses in groups.

Keeping horses in groups is widely recommended but limited information is available about how this is implemented in practice. The aim of this survey was to describe how horses are kept in the Nordic countries in relation to sex, age, breed, and equestrian discipline and to assess owners' attitudes toward keeping horses in groups. Horse owners in Denmark, Finland, Norway, and Sweden were approached using a web-based questionnaire, which was translated into 4 languages and distributed online via equestrian forums, organizations, and social media. The number of respondents was 3,229, taking care of 17,248 horses. Only 8% of horses were never kept in groups, 47% were permanently grouped for 24 h/d, and 45% were stabled singly but grouped during turnout. Yearlings were most often permanently kept in groups (75%), mares and geldings more commonly during parts of the day (50 and 51%, respectively), and stallions were often kept alone (38%). Icelandic horses were more likely to be permanently kept in groups (36%) than warmbloods (16%) and ponies (15%). Twice as many competition horses (51%) were never grouped compared with horses used for breeding (20%) or leisure purposes (15%). The majority of respondents (86%) strongly agreed that group housing benefits horse welfare and that it is important for horses to have the company of conspecifics (92%). Nevertheless, not all horses were kept in groups, showing that attitudes toward group housing may not necessarily reflect current management. The risk of injury was a concern of many respondents (45%), as was introducing unfamiliar horses into already established groups (40%) and challenges in relation to feeding in groups (44%). Safety of people (23%) and difficulties handling group-kept horses (19%) were regarded as less problematic. Results suggest that the majority of horses have the possibility to freely interact with other horses, either as fulltime members of a group during 24 h/d or during turnout. Future research should address the extent to which being a part-time member of a group affects horse welfare. For permanent group housing to become more widespread, such as it is the case for most farm animals, future research could focus on solving some of the reoccurring problems perceived with keeping horses in groups. The dissemination of evidence-based information on all aspects around keeping horses in groups can ultimately stimulate further positive changes in the management of group-kept horses.

Health-related quality of life (HRQL) in immunodeficient adults with selective IgA deficiency compared with age- and gender-matched controls and identification of risk factors for poor HRQL.

PURPOSE: Selective IgA deficiency (SIgAD) is the most common primary immunodeficiency with a prevalence of 1/600 in the general population. Any targeted health-related quality of life (HRQL) study of adults with SIgAD has never been presented. The objectives of the study were to compare HRQL between SIgAD adults and randomly selected age- and gender-matched population controls, and to identify risk factors for poor HRQL. METHODS: Thirty-two SIgAD individuals and 63 controls answered three questionnaires (clinical data, Short Form-36 Health Survey (SF-36), infection-related HRQL) at baseline before undergoing medical/dental examinations and laboratory assessments. HRQL in SIgAD was re-evaluated after 6 and 12 months. RESULTS: Baseline: Selective IgA deficiency individuals reported significantly increased fear of contracting infections (p < 0.01). Those scoring high on fear also perceived significantly poorer physical health (p < 0.01). SF-36 results indicated that SIgAD individuals perceived poorer HRQL, although this was not statistically significant. FOLLOW-UP: Compared with SF-36 responses at baseline, SIgAD individuals reported significantly more pain (p < 0.01) at 6 months, poorer general health (p < 0.05) and summarised physical HRQL (p < 0.01) at 6 and 12 months and decreased vitality at 12 months. The summarised mental scale remained stable over time. Risk factors for poor HRQL: The number of antibiotic treatments during the previous year (p < 0.001), number of daily medications (p < 0.01), allergic rhinoconjunctivitis (p < 0.05), chronic musculoskeletal symptoms at least every week (p < 0.05) and anxiety and/or insomnia (p < 0.05) were identified as independent risk factors for poor HRQL. CONCLUSION: The study highlights the importance of identifying and thoroughly evaluating, educating and following up individuals with SIgAD, as their HRQL may be negatively affected due to health problems possible to prevent and treat.

Clinical symptoms in adults with selective IgA deficiency: a case-control study.

Selective IgA deficiency (SIgAD) is the most common primary immunodeficiency in Caucasians with a prevalence of 1/600 and is generally considered a mild disorder. In this study, the clinical status of 32 adults with SIgAD was investigated and compared to 63 age- and gender matched controls, randomly selected from a population database. The SIgAD individuals reported significantly more often contracting various upper and lower respiratory infections, with 8 (25.0 %) having been diagnosed with ≥1 pneumonia in the preceding two years, compared to one (1.6 %) control (p < 0.001). Furthermore, the SIgAD individuals were found to have increased proneness to infections and increased prevalence of allergic diseases and autoimmunity, with a total of 84.4 % being affected by any of these diseases, compared to 47.6 % of the controls (p < 0.01). This study challenges the common statement of SIgAD being a mild form of immunodeficiency. It also highlights the importance of using matched controls in PID clinical research to better detect clinically important manifestations.

Neonatal piglet traits of importance for survival in crates and indoor pens.

The primary aim of the present study was to investigate whether the same piglet traits contributed to the same causes of neonatal piglet mortality in crates (CT) and pens (PN). Gilts originating from 2 distinct genetic groups that differed in breeding value for piglet survival rate at d 5 (SR5) were used. These were distributed to farrow in either PN or CT as follows: high-SR5 and CT (n = 30); low-SR5 and CT (n = 27); high-SR5 and PN (n = 22); and low-SR5 and PN (n = 24). Data on individual piglets were collected at birth, including interbirth interval; birth order; birth weight; rectal temperature at birth, 2 h after birth, and 24 h after birth; cordal plasma lactate; and latency to first suckle. Based on autopsy, causes of mortality were divided into stillborn, bitten to death, starvation, crushed, disease, and other causes. Potential risk factors of dying were estimated using a GLM with a logit link function. No significant effect (NS) of housing was observed on the odds of a piglet being stillborn (F(1,73) = 0.1, NS), being crushed (F(1,53) = 1.4, NS), or dying of starvation (F(1,53) = 0.3, NS). No significant differences were observed between the 2 genetic groups for any category of mortality. Piglet traits for pre- and postnatal survival were the same for CT and PN. The odds of being stillborn were increased in piglets born late in the birth order (F(1,1061) = 33.5, P < 0.0001), after a long interbirth interval (F(1,1061) = 19.2, P < 0.0001), and with a lighter birth weight (F(1,1061) = 9.2, P = 0.003). The lighter the birth weight of the piglets, the greater were the odds of being crushed (F(1,1050) = 18, P < 0.0001) and dying of starvation (F(1,1050) = 19, P < 0.0001). The lower the rectal temperature 2 h after birth, the greater were the odds of being crushed (F(1,1050) = 4.6, P = 0.03), starving (F(1,1050) = 16.6, P < 0.0001), or dying of diseases (F(1,1050) = 4.9, P = 0.03). Increased cordal plasma lactate increased the odds of dying from starvation (F(1,1050) = 18, P < 0.0001). In both CT and PN, the birth weight, body temperature 2 h after birth, and birth process were important traits related to crushing, starvation, and disease. Neither housing nor breeding value influenced mortality or traits of importance for the inborn viability of piglets. The results emphasize that the microclimate in the PN for newborn piglets and its heat-preserving properties are more important for survival than whether the sow is crated or penned.

Primary immunodeficiency and autoimmunity: lessons from human diseases.

Primary immunodeficiency diseases (PID) are a genetically heterogenous group of >150 disorders that affect distinct components of the innate and adaptive immune system and are often associated with autoimmune diseases. We describe PID affecting T-regulatory cells, complement and B cells or their products and discuss the possibility of a cause-effect relationship. The high concordance of T-regulatory cell defects to organ-specific autoimmune disease implies an obligatory role of these cells in maintaining tolerance to epithelial and endocrine tissues; the absence of central nervous system involvement may reflect immunological privilege. Congenital defects in C1q, C1r/s and C4 are strongly associated with systemic lupus erythematosus (SLE), and this pattern along with laboratory evidence suggests a major importance of classical pathway activity in safe elimination of immune complexes and prevention of immune complex disease (ICD). It is debatable whether this ICD is to be regarded as an autoimmune disease (resulting from a breakdown of immunological ignorance to antigens that are normally hidden), as autoantibodies may be absent, and tissue damage because of deposition of immune complexes could account for all of the pathology observed. Evidence for a causative link between primary antibody deficiencies and autoimmune disease is much less compelling and may in fact involve a common genetic background. However, arguments have also been made in favour of the notion that an intense antigen load as a result of recurrent or persistent infections may affect either tolerance or ignorance, e.g. by molecular mimicry or the presence of superantigens. Similar immunological mechanisms might account for the vast majority of autoimmune diseases.

Use of 360-degree assessment of residents in internal medicine in a Danish setting: a feasibility study.

BACKGROUND: The aim of the study was to explore the feasibility of 360 degree assessment in early specialist training in a Danish setting. Present Danish postgraduate training requires assessment of specific learning objectives. Residency in Internal Medicine was chosen for the study. It has 65 learning objectives to be assessed. We considered 22 of these suitable for assessment by 360-degrees assessment. METHODS: Medical departments of six hospitals contributed 42 interns to the study. Each resident was assessed by ten persons of whom one was a secretary, four were nurses and five senior doctors. The assessors spent 14.5 minutes (median) to fill in the forms. RESULTS: Of the 22 chosen objectives, 15 could reliably be assessed by doctors, 7 by nurses and none by secretaries. CONCLUSIONS: The method was practical in busy clinical departments and was well accepted by the assessors. Reliability of the method was acceptable. It discrimintated satisfactorily between the good and not so good performers.

Estimating the risk of long-term erectile, urinary and bowel symptoms resulting from prostate cancer treatment.

Reports on long-term complications resulting from treatment for localized prostate cancer are very inconsistent. In order to estimate the risks of long-term erectile dysfunction, urine symptoms and bowel symptoms following prostatectomy (RP), external conventional or conformal beam radiation (ERT or CRT) and brachytherapy (BRT), 98 papers from the PubMed and Cochrane Clinical Trial databases were selected, reviewed and critically evaluated. The majority of papers were institution-based retrospective and prospective follow-up studies; only two of these studies measured the risk of developing more than one treatment complication. Due to differences in study designs and populations, it is difficult to directly compare studies and not meaningful to calculate summary estimates. In addition to focusing on randomized clinical trials and well-designed population based studies, future research should adopt standardized methodologies and should measure the risk of developing more than one treatment complication.

Influence of the calcium content of the diet offered to leopard tortoises (Geochelone pardalis).

Twenty-four juvenile leopard tortoises were divided into four groups of six; one group was fed a basic low-calcium feed for six months, and the other three groups were fed the same basic diet supplemented with one, three and nine times the amount of calcium recommended as a supplement to the diet of reptiles. The animals' bone mineral content and bone mineral density were estimated by dual energy x-ray absorptiometry, and blood samples were taken at the start and at the conclusion of the study. One tortoise from each group was examined postmortem. There was a clear depletion of calcium in the body of the tortoises receiving no calcium supplement, and the shell of the tortoises receiving the recommended calcium supplement did not calcify to the extent expected. The tortoises that received three times the recommended calcium supplementation had the highest growth rate and were thriving. However, metastatic calcifications were observed postmortem in the two groups that were given the highest doses of calcium.

Mortality and cancer morbidity in a cohort of Canadian petroleum workers.

AIMS: To assess mortality and cancer morbidity in Canadian petroleum workers and explore exposure-response relations for specific petroleum agents. METHODS: A total of 25 292 employees hired between 1964 and 1994 were linked to the Canadian tumour registry and national mortality database. Exposure-response trends were assessed for hydrocarbon solvents/fuels, hydrocarbon lubricants, petroleum coke/spent catalyst, and hydrogen sulphide (H2S). RESULTS: External comparison analyses (mortality and incidence) showed deficits for all causes and all malignant neoplasms combined and were consistent with expectation for most malignant and non-malignant sites analysed. Gall bladder cancer mortality was increased among males based on four deaths, but cases had no common job assignments and the increase was focused in workers employed <10 years. Mesothelioma incidence was increased. Most exposure-specific analyses were compromised by small numbers. Statistically significant increases were observed for H2S exposure and a subgroup of accidental deaths as well as for petroleum coke/spent catalyst exposure and lung cancer. While both findings have a degree of biologic plausibility, the H2S association, which exhibited a clearer exposure-response pattern, could be subject to unmeasured confounders. Additionally, interpretation was complicated by the high correlation between hydrocarbon and H2S exposures. With regard to lung cancer, the analysis could not adequately control for smoking, was based on small numbers, and exhibited a tenuous exposure-response pattern. CONCLUSION: The findings for mesothelioma suggest the need for continued attention to asbestos in the petroleum industry. The relation between accidental deaths and H2S exposure deserves closer scrutiny in similarly exposed populations. Further analyses of lung cancer are underway and will be reported separately.

Human polyomavirus BK (BKV) and neuroblastoma: mechanisms of oncogenic action and possible strategy for novel treatment.

BACKGROUND: We reported previously that nearly all human neuroblastomas analyzed contain and express genomic DNA sequences deriving from the human polyomavirus BK (BKV) [Flaegstad et al.: Cancer Res 59:1160-1163, 1999]. PROCEDURE: Here we show that the BKV large T antigen is expressed and bound to p53 in neuroblastoma cells and that this interference compromises the tumor suppressor function of p53. RESULTS: Treatment of neuroblastoma cells with large T antigen antisense constructs relocated active p53 to the nucleus. The relocation event was accompanied by enhanced p21(waf1/cip1) expression as well as induced apoptosis. CONCLUSIONS: Continuous antisense oligonucleotide treatment of nude rats with human neuroblastoma xenografts resulted in a significant but incomplete reduction of tumor growth compared to rats treated with saline.

p53-mediated negative regulation of stathmin/Op18 expression is associated with G(2)/M cell-cycle arrest.

Utilizing the technique of differential display of mRNA, we have identified p53-responsive genes that are transcriptionally up- or down-regulated as cells enter growth arrest. One gene that was down-regulated, pong16, was found to be identical to stathmin/Op18, a protein involved in the regulation of microtubule dynamics. Evidence that p53 is directly or indirectly involved in negative regulation of stathmin/Op18 expression includes the following: (i) p53-mediated growth inhibition is associated with repression of stathmin/Op18 expression following serum stimulation, (ii) reporter gene assays revealed p53-mediated repression of stathmin/Op18 promoter activity and (iii) constitutive over-expression of stathmin/Op18 bypasses a p53-mediated G(2)/M arrest in the cell cycle. These results suggest that p53-mediated negative regulation of stathmin/Op18 plays an important role in cell-cycle control.

Updated mortality among diverse operating segments of a petroleum company.

OBJECTIVES: To update mortality for 34 560 employees from diverse operating segments of a Canadian petroleum company; and to investigate potential relations with occupational factors. METHODS: Employees from 1964-83 were linked to the Canadian mortality data base to provide 11 years additional follow up. There were 6760 deaths and 750 683 person-years of follow up compared with 3909 and 428 190, respectively, in the earlier study. Analyses used standardised mortality ratios (SMRs) to compare worker cause specific mortality with the Canadian general population. Duration of employment and latency analyses were performed for causes previously found to be increased in this and other petroleum cohorts, as well as any findings of interest. RESULTS: For the period 1964-94, employees experienced significantly low overall mortality (SMR=0.86 men, SMR=0.80 women). Kidney cancer, which has been increased in some studies of petroleum workers, was not increased. Acute non-lymphocytic leukaemia in exposed operating segments was consistent with the expected or only slightly, non-significantly increased. The most notable finding was increased deaths from mesothelioma among refinery and petrochemical workers (SMR 8.68; 95% confidence interval (95% CI) 5.51 to 13.03), most of whom were long term employees in jobs with presumed exposure to asbestos (mechanical and pipefitters). Deaths from multiple myeloma among marketing and distribution workers, which were previously increased, remained increased (SMR 2.08; 95% CI 0.95 to 3.95) in the update period 1984-94; however, there was no clear pattern by duration of employment or latency. Aortic aneurysms, which also were previously significantly increased among marketing and distribution workers approached the expected in the update period (SMR 1.18; 95% CI 0. 65-1.98). Analyses by duration of employment showed suggestive trends for aortic aneurysms, but earlier studies of this cohort have not found a relation between aortic aneurysms and exposure to hydrocarbons. CONCLUSION: The additional 2851 deaths and 322 493 person-years of follow up strengthened the assessment of mortality patterns relative to occupational factors. With the exception of mesothelioma, no clear work related increases in disease were identified.