Biomedical subjects

T Skov

Publications and source records attributed to T Skov.

At least 19 recordsLinked to original sources

PubMed2002

A phase II trial of the vitamin D analogue Seocalcitol (EB1089) in patients with inoperable pancreatic cancer.

Inoperable cancer of the exocrine pancreas responds poorly to most conventional anti-cancer agents, and new agents are required to palliate this disease. Seocalcitol (EB1089), a vitamin D analogue, can inhibit growth, induce differentiation and induce apoptosis of cancer cell lines in vitro and can also inhibit growth of pancreatic cancer xenografts in vivo. Thirty-six patients with advanced pancreatic cancer received once daily oral treatment with seocalcitol with dose escalation every 2 weeks until hypercalcaemia occurred, following which patients continued with maintenance therapy. The most frequent toxicity was the anticipated dose-dependent hypercalcaemia, with most patients tolerating a dose of 10-15 microg per day in chronic administration. Fourteen patients completed at least 8 weeks of treatment and were evaluable for efficacy, whereas 22 patients were withdrawn prior to completing 8 weeks' treatment and in 20 of these patients withdrawal was due to clinical deterioration as a result of disease progression. No objective responses were observed, with five of 14 patients having stable disease in whom the duration of stable disease was 82-532 days (median=168 days). The time to treatment failure (n=36) ranged from 22 to 847 days, and with a median survival of approximately 100 days. Seocalcitol is well tolerated in pancreatic cancer but has no objective anti-tumour activity in advanced disease. Further studies are necessary to determine if this agent has any cytostatic activity in this malignancy in minimal disease states.

Administration, Oral↗

PubMed1999

CHS 828, a novel pyridyl cyanoguanidine with potent antitumor activity in vitro and in vivo.

A new class of recently discovered antineoplastic agents, the pyridyl cyanoguanidines, exert a potent antitumor activity in rodents after oral administration. Optimization in vitro and in vivo has resulted in the selection of the lead candidate CHS 828 (N-(6-chlorophenoxyhexyl)-N'cyano-N"-4-pyridylguanidine). CHS 828 was found to exert potent cytotoxic effects in human breast and lung cancer cell lines, with lesser effects on normal fibroblasts and endothelial cells. In a study using a panel of cell lines with different resistance patterns, the effects of CHS 828 showed a low correlation with the activity patterns of known anticancer agents, and no sensitivity to known mechanisms of multidrug resistance was observed. In nude mice bearing human tumor xenografts, CHS 828, at doses from 20 to 50 mg/kg/day p.o., inhibited the growth of MCF-7 breast cancer tumors and caused regression of NYH small cell lung cancer tumors. Oral administration of CHS 828 once weekly improved efficacy without increasing toxicity. CHS 828 was found to compare favorably with established chemotherapeutic agents such as cyclophosphamide, etoposide, methotrexate, and paclitaxel. In mice with NYH tumors, long-term survival (>6 months) was observed after treatment with CHS 828 was stopped. In conclusion, CHS 828 is an effective new antitumor agent, with a potentially new mechanism of action. CHS 828 is presently being tested in Phase I clinical trials in collaboration with the European Organization for Research and Treatment of Cancer.

Animals↗

PubMed1999

Evaluation of the revised NIOSH lifting equation. A cross-sectional epidemiologic study.

STUDY DESIGN: A cross-sectional study of the 1-year prevalence of low back pain was conducted in workers employed in manual lifting jobs. OBJECTIVES: To provide epidemiologic data to determine the correlation between the prevalence of low back pain and exposure to manual lifting stressors, measured with the lifting index component of the revised lifting equation from the National Institute for Occupational Safety and Health (NIOSH). SUMMARY OF BACKGROUND DATA: The NIOSH lifting equation has been proposed as a practical, yet valid tool for assessing the risks of low back pain caused by manual lifting. To date, however, there have been few studies in which the effectiveness of the equation to identify jobs with elevated rates of low back pain has been evaluated. METHODS: Fifty jobs from four industrial sites were evaluated with the NIOSH lifting equation. A symptom and occupational history questionnaire was administered to 204 people employed in lifting jobs and 80 people employed in nonlifting jobs. Regression analysis was used to determine whether there was a correlation between the lifting index and reported low back pain. RESULTS: As the lifting index increased from 1.0 to 3.0, the odds of low back pain increased, with a peak and statistically significant odds ratio occurring in the 2 < lifting index < or = 3 category (odds ratio = 2.45). For jobs with a lifting index higher than 3.0, however, the odds ratio was lower (odds ratio = 1.45). CONCLUSIONS: Although low back pain is a common disorder, the lifting index appears be a useful indicator for determining the risk of low back pain caused by manual lifting.

Adult↗

PubMed1999

Visual analogue scales for detecting changes in symptoms of the sick building syndrome in an intervention study.

OBJECTIVES: This study tested questionnaires using visual analogue scales (VAS) in a cleaning intervention study and attempted to find a simple way of analyzing the replies to the questionnaires. METHODS: A VAS questionnaire made up of 26 questions was developed and marked once a week for 28 weeks by the room occupants in 3 buildings. A total of 1248 questionnaires was used in the analysis of the results. A simple model based on the differences between a person's average responses during 2 different periods was used in the analysis. RESULTS: No clear effect of the cleaning was found. Several significant correlations between different questions were established. Estimates for the design of future studies are given. CONCLUSIONS: The VAS questionnaire proved to be feasible for this type of study. It is suggested that each intervention period should last 4 weeks if the questionnaire is used once a week. However, the length of the period also depends on the expected latency of the symptoms, on how long it takes for environmental conditions to be affected by the intervention, and on how quickly conditions return to "normal" during control periods.

Adult↗

PubMed1998

Injuries among domestic waste collectors.

Detailed information on occupational injuries and the precise number of injuries among waste collectors is missing. In this study, risk circumstances associated with injuries among waste collectors were analyzed and described. The study was carried out in a single company with 667 employees in 1993. For each injury, information was collected on date, time, type, and severity of the injury, injury circumstances, department of employment, external or internal registration, sex, year of birth and employment, type of employment, and a registration of where the injury happened. A total of 17% of the employees experienced injury. The number of injuries decreased with increasing seniority and age. Most injuries occurred outside the company area. More injuries occurred on Mondays and Thursdays, and there were peaks in the injury rate in May and September. Most often injured was the back, followed by the knees, hands, and feet. The job as a waste collector was associated with a high risk of experiencing an occupational injury and the number of injuries decreased with increasing seniority and nonsignificantly with increasing age. Moreover, a seasonal and weekly variation was observed.

Accidents, Occupational↗

PubMed1998

Effect of age and height on vibrotactile threshold among 1,663 U.S. workers.

Assessment of vibrotactile threshold has gained application in studies of neuropathies induced by toxic substances, compression, and vibration. The effect of age and height on vibrotactile threshold is of interest for its own sake and for the purpose of confounder control. We have studied the relation between finger and toe vibrotactile thresholds and age and height in five studies carried out by the National Institute for Occupational Safety and Health with vibrometry data (N = 1,663). A unique property of the merged data set was its wide age range from 14 to 82 years (mean 42 years). We demonstrate a J-shaped increase in finger threshold value (expressed on a log scale) with age, with no increase up to age 35 and a linear increase thereafter. For finger threshold, height was not an important predictor. The data were sparser (n = 541) for toe threshold but suggested a linear increase with both age and height. While consistent with prior data, this study provides a better understanding of the relation between vibrotactile threshold and age and height than has been available before. The greater effect of age and height on toe rather than finger threshold is consistent with the hypothesis that the length of the nerve increases susceptibility to peripheral neuropathy.

Adolescent↗

PubMed1998

Prevalence proportion ratios: estimation and hypothesis testing.

BACKGROUND: Recent communications have argued that often it may not be appropriate to analyse cross-sectional studies of prevalent outcomes with logistic regression models. The purpose of this communication is to compare three methods that have been proposed for application to cross sectional studies: (1) a multiplicative generalized linear model, which we will call the log-binomial model, (2) a method based on logistic regression and robust estimation of standard errors, which we will call the GEE-logistic model, and (3) a Cox regression model. METHODS: Five sets of simulations representing fourteen separate simulation conditions were used to test the performance of the methods. RESULTS: All three models produced point estimates close to the true parameter, i.e. the estimators of the parameter associated with exposure had negligible bias. The Cox regression produced standard errors that were too large, especially when the prevalence of the disease was high, whereas the log-binomial model and the GEE-logistic model had the correct type I error probabilities. It was shown by example that the GEE-logistic model could produce prevalences greater than one, whereas it was proven that this could not happen with the log-binomial model. The log-binomial model should be preferred.

Cross-Sectional Studies↗

PubMed1997

Comparison of a self-administered questionnaire and a telephone interview of 146 Danish waste collectors.

Methods to collect epidemiologic data include, among other means, self-administered questionnaires and personal and telephone interviews. In some studies, these data collection methods are used simultaneously. However, little is known about the comparability of the data obtained, thus, the validity of pooling data. A self-administered questionnaire was completed by 146 waste collectors, who participated in a telephone interview 3 months later. The responses to health questions were compared. Agreement percentages and kappa values were calculated. An answer pattern shift was detected in a subgroup of questions with five answer options. Grouping the answer options diminished the shift in the answer pattern. The questions in a yes/no format generally showed no shift in the answer pattern. The study indicates that caution should be exercised when pooling data collected by self-administered questionnaire and telephone interview in epidemiological research. Some types of questions seem to be sensitive to the data collection method.

Adult↗

PubMed1997

Comparison of the reproducibility of the WHO classifications of 1975 and 1994 of endometrial hyperplasia.

In a blinded, randomized design, six histopathologists with an interest in gynecological pathology examined the inter- and intraobserver variation of the histopathological diagnosis of endometrial hyperplasia according to the World Health Organization (WHO) classification of 1975 and the new WHO classification of 1994. On four occasions, the pathologists assessed hematoxylin/eosin-stained slides from 128 cases originally diagnosed and coded in the Snomed system as endometrial hyperplasia. In the first and third rounds, the slides were classified according to the 1975 classification and in the second and fourth rounds according to the 1994 classification. The overall interobserver agreement in the two rounds where the 1975 classification was used was 0.47 and 0.51, and the kappa values 0.24 [95% confidence interval (CI) 0.21-0.27] and 0.30 (95% CI 0.27-0.33). The overall interobserver agreement in the two rounds using the 1994 classification was 0.45 and 0.41 and the kappa values 0.25 (95% CI 0.23-0.28) and 0.20 (95% CI 0.17-0.22). Reducing the classification to two categories with clinical significance (atypical endometrial hyperplasia versus others in the 1975 classification, and atypical endometrial hyperplasia, complex versus others in the 1994 classification) increased the overall agreement of the 1975 classification in both rounds to 0.91 and of the 1994 classification to 0.92 and 0.90. The kappa values increased to 0.54 (95% CI 0.49-0.58) and 0.49 (95% CI 0.45-0.54) in the 1975 classification and to 0.59 (95% CI 0.54-0.63) and 0.42 (95% CI 0.37-0.46) in the 1994 classification. The intraobserver overall agreement for the 1975 classification ranged from 0.80 to 0.55 and the kappa values from 0.70 (95% CI 0.58-0.81) to 0.28 (95% CI 0.17-0.39). The intraobserver overall agreement for the 1994 classification ranged from 0.71 to 0.46 and the kappa values from 0.60 (95% CI 0.51-0.70) to 0.20 (95% CI 0.09-0.30). It is concluded that there is considerable inter- and intraobserver variation using both the 1975 and the 1994 classifications of endometrial hyperplasia. We propose that there is need for a specification and for a simplification of the classification.

Double-Blind Method↗

PubMed1997

Season, equipment, and job function related to gastrointestinal problems in waste collectors.

OBJECTIVES: Informal reports have suggested that work as a waste collector entails exposures that cause gastrointestinal symptoms--such as nausea and diarrhoea. This study explores this hypothesis by correlating data on the type of waste collected, the persons' job function, the equipment used, and the times of the week and the year of reported nausea and diarrhoea. METHODS: 1747 male waste collectors and a control group for comparison of 1111 male municipality workers answered a questionnaire on work environment, work related exposure, and health status. RESULTS: In a multivariate analysis collection of organic and residual waste (prevalence proportion ratio (PPR) 1.45) and mixed household waste (PPR 1.43) were associated with reported nausea and so was the job loader (PPR 1.51). More symptoms were reported in the summer. Multivariate analysis of diarrhoea showed that the job front runner was associated with reported diarrhoea (PPR 1.22) and so was the job loader (PPR 1.26). More symptoms occurred in the summer. The workers stated that the gastrointestinal symptoms were related to the smell of rotten waste. This may support the hypothesis that microbial compounds were the causal agents. CONCLUSION: The gastrointestinal symptoms were associated with the job of waste collector and moreover the symptoms predominantly occurred in the summer.

Adult↗

PubMed1996

Etiologic and prevention effectiveness intervention studies in occupational health.

In this article a basic distinction is made between etiologic and prevention effectiveness intervention studies. Etiologic intervention studies focus on elucidating causes of disease, while the purpose of prevention effectiveness intervention studies is to study methods of prevention. The design requirements for each of these studies are very different: etiologic intervention studies usually need large study populations, large exposure contrasts, ascertainment of exposure, as well as health outcome. Ideally, randomization and blinding should also be applied. Effective preventive strategies may, on the other hand, be identified in small study populations with exposure as the only outcome measure, and randomization and blinding may be superfluous. At present, intervention studies are in great demand, and often there is a wish that etiologic questions as well as prevention effectiveness be addressed in the same study. We argue that this should not be done without careful consideration of possible conflicting design aspects.

Bias↗

PubMed1996

Psychosocial and physical risk factors for musculoskeletal disorders of the neck, shoulders, and lower back in salespeople.

OBJECTIVES: To analyse the association between symptoms from the musculoskeletal system and many psychosocial and other physical stressors in the job demand-control-support model. Also to analyse the influence of personality characteristics. METHODS: 1306 salespeople answered a self administered questionnaire on job characteristics, exposures, personality characteristics, social network, smoking and drinking habits, and symptoms of the neck, shoulders, and low back. RESULTS: In multivariate analyses, high job demands were related to neck and shoulder symptoms (ORs 1.43-1.47 in the highest exposure groups compared with the lowest), and tendency to become overworked and lack of social support from colleagues were related to back pain (OR 1.81-2.04 in the highest exposure groups compared with the lowest). Lack of variation in the job, low control over time, and high competition were related to neck symptoms, but there was an interaction so that both low control over time and high competition had to be present to increase the OR. Also, driving long distances and sedentary work were related to neck and low back pain, and time spent in the car to shoulder pain (ORs 1.64-2.80 in the three highest groups v the lowest exposure groups). CONCLUSION: Both psychosocial and physical factors were associated with musculoskeletal symptoms. Many dimensions of the demand-control-support model were associated with symptoms. Only one personality characteristic, tendency to feel overworked, significantly influenced the prevalence of musculoskeletal symptoms.

Adult↗

PubMed1996

Underreporting of occupational cancers in Denmark.

OBJECTIVES: The goal of the study was to investigate whether the reporting of occupational cancers has improved in Denmark since 1987 and whether medical records currently have better information on occupational exposures. METHODS: All cases of pleural mesothelioma and sinonasal adenocarcinoma and 766 randomly selected adenocarcinomas of the lung diagnosed between 1983 and 1990 were identified from the Cancer Register. These cases were traced in the Register of Reported Occupational Diseases and in the records of the National Board of Industrial Injuries. Medical records for patients not reported to the Register of Reported Occupational Diseases were requested from hospitals and the data on work-related exposure were retrieved. RESULTS: For pleural mesotheliomas the frequency of reporting increased from 43% in 1983-1987 to 53% in 1988-1990. The frequency of reporting of sinonasal adenocarcinomas decreased from 34 to 20% in these periods. Of the adenocarcinomas of the lung, 1% had been reported. CONCLUSION: Overall the reporting of occupational cancer has not improved in Denmark since 1987.

Adenocarcinoma↗

PubMed1995

National survey on the use of chemicals in the working environment: estimated exposure events.

OBJECTIVES: To obtain knowledge about the use and distribution of hazardous chemicals in Danish industry. This knowledge is used to regulate the occupational environment and prevent hazardous exposure. METHODS: A national survey on the use of chemicals was carried out in 1989 in a stratified sample of 1448 Danish businesses. 13,000 different chemical products were reported. Information on components in the chemical products was obtained from the Danish product register data base (PROBAS) and by inquiries to suppliers and manufacturers. At the end of the study the composition of about 9400 of the products was known. A model was developed to estimate national numbers of chemical exposure events as a supplement to data on weights of chemicals used. RESULTS: Data are presented for 36 chemical substances with chronic toxic effects and high estimated national numbers of exposure events for the industry groups included in the survey. Seven of the 36 substances are carcinogens, 17 are reproductive toxicants, 12 are allergens, and 18 are neurotoxicants according to listings of chronic toxicants used by the Danish authorities. The largest national number of exposure events was estimated for the industry groups manufacture of fabricated metal products, and personal services, cleaning, and hair dressing. These should have special attention in further preventive work. CONCLUSIONS: This survey on the use of chemicals is the first nationwide investigation in Denmark to delineate the use of all chemicals. The data have been used in a project to review occupational hazards in general in Danish industry. In the future, the data may be used as a basis for measuring chemical substitution, developing chemical safety, and as reference for more specific investigations and for follow up studies. Also job exposure matrices based on actual use of chemical products can be constructed.

Allergens↗

PubMed1995

Musculoskeletal symptoms among sewing machine operators.

OBJECTIVES: A longitudinal study was conducted to describe the prevalences and development of musculoskeletal symptoms among sewing machine operators in relation to age and exposure and among former sewing machine operators who changed exposure by changing occupation. METHODS: Musculoskeletal symptoms were assessed among 327 sewing machine operators in 1985 with the use of the standardized Nordic questionnaire. A follow-up study in 1991 showed that approximately one-third was still working as a sewing machine operator, one-third had changed occupation, and the rest were out of employment. The exposure was assessed by a questionnaire regarding the type of machine being operated, work organization, workplace design, units produced per day, and payment system. RESULTS: High prevalences of musculoskeletal symptoms of the neck and shoulders were found, with some associations to exposure variables such as efficiency. Initially symptom-free sewing machine operators were not at a higher risk of developing symptoms when they continued sewing during the six-year follow-up when compared with those who changed to other employment. However, symptomatic sewing machine operators who quit sewing were much more likely to be relieved of their symptoms than were symptomatic operators who continued sewing, odds ratio 3.26 [95% confidence interval (95% CI) 1.38-7.72] for 12-month symptoms and odds ratio 3.90 (95% CI 1.28-11.90) for 7-day symptoms. This trend also applied to long-lasting symptoms. CONCLUSIONS: The results demonstrate that, for many sewing machine operators, neck and shoulder symptoms are reversible and may be influenced by reallocation to other worktasks.

Adolescent↗

PubMed1994

Age-period-cohort modelling of large-bowel-cancer incidence by anatomic sub-site and sex in Denmark.

In a previous investigation, statistical modelling was used to examine the relationship between large-bowel-cancer incidence and age, time period and birth cohort by anatomic sub-site and sex, using data from the Connecticut Tumor Registry (CTR) for the period 1950 to 1984. This analysis revealed differences in age-period-cohort patterns that suggested etiologic distinctions among sub-site groupings and between the sexes. To test the generalizability of the Connecticut findings, we have conducted a similar age-period-cohort analysis using data from the Danish Cancer Registry (DCR) for the period 1953 to 1987. Cancers of the large bowel were classified into 6 anatomic sub-sites: cecum, ascending colon, transverse colon, descending colon, sigmoid colon and rectum. Data were fitted to log-linear age-period-cohort models. If we interpret differences in age-period-cohort patterns as reflecting etiologic distinctions, the Denmark analysis, in conjunction with the Connecticut findings, was consistent with there being etiologic distinctions between cancers of the colon vs. the rectum in both males and females, between cancers of the cecum and the ascending colon vs. the remainder of the colon in females and between males vs. females for cancers of the sigmoid colon and rectum. Cancers of the cecum and the ascending colon were the most similar between males and females. Due to the ambiguities of age-period-cohort modelling, these should be considered only tentative conclusions that can be tested by analytical epidemiologic studies.

Adult↗

PubMed1994

Are pathologists biased by clinical information?: A blinded cross-over study of the histopathological diagnosis of mesothelial tumours versus pulmonary adenocarcinoma.

In a blinded cross-over design, we studied whether three pathologists were biased by clinical information when making histopathological diagnoses of adenocarcinoma of the lung and benign and malignant mesothelial tumours. Furthermore, the interobserver variation of these diagnoses was assessed. Forty-one cases of adenocarcinoma of the lung and mesothelial tumours were assessed by three pathologists in four rounds. In the first two rounds, slides stained by H&E and clinical information were available. Slides and information were matched so that a specific slide in one round was given clinical information suggesting adenocarcinoma and in the other round, the clinical information suggested mesothelial tumour. In the third and fourth rounds, a panel of immunohistochemical stains was added. The clinical information was matched in the same way as in the first and second rounds. Bias by clinical information was observed when the diagnoses were made on slides stained by H&E, while no bias could be demonstrated when immunohistochemical reactions were included. The reproducibility also improved significantly when these slides were available.

Adenocarcinoma↗

PubMed1994

Differentiation of adenocarcinoma of the lung and malignant mesothelioma: predictive value and reproducibility of immunoreactive antibodies.

A panel of antibodies against keratins, epithelial membrane antigen (EMA), epithelial antigen (Ber-EP4), carcinoembryonic antigen (CEA), tumour-associated glycoprotein (B72.3), vimentin and LeuM1 was applied to sections of adenocarcinoma of the lung and malignant mesothelioma in a randomized design. The proportion of stained tumour cells within each section was estimated independently in five categories by three pathologists (no positive tumour cells, 1-10%, 11-33%, 34-66% and more than 67% positive tumour cells). The kappa values representing the chance corrected interobserver agreement for the different antibodies in such a five group assessment were between 0.38 and 0.72. In two group assessment the kappa values were between 0.53 and 0.94. Nosological sensitivity and nosological specificity were calculated for all antibodies, and diagnostic sensitivity and diagnostic specificity (predictive values) were calculated for the Ber-EP4, CEA, B72.3, LeuM1 and vimentin. The difference between nosological sensitivity and nosologic specificity and the clinically relevant predictive values of positive and negative tests were demonstrated. In respect of the reproducibility and the diagnostic power defined by the predictive values, we demonstrated that a panel of antibodies, including CEA, Ber-EP4 and B72.3 and, to a lesser degree, LeuM1 and vimentin is applicable for the histopathological distinction between adenocarcinoma of the lung and malignant mesotheliomas. Before introduction of new diagnostic tests, including new antibodies, the prevalence of the tested tumours should be estimated. Nosological sensitivity and nosological specificity should be converted to predictive values.

Adenocarcinoma↗