Antiarrhythmic properties of acetaminophen in the dog.

Mongrel dogs bred for research and weighing 25 +/- 3 kg were used to test the hypothesis that acetaminophen has antiar-rhythmic properties. Only ventricular arrhythmias defined by the Lambeth Conventions were investigated. Dogs were exposed either to 60 mins of regional myocardial ischemia followed by 180 mins of reperfusion (n = 14) or were administered a high dose of ouabain (n = 14). Both groups of 14 dogs were further divided into vehicle and acetaminophen treatment groups (n = 7 in each). During selected 10-min intervals, we recorded the numbers of ventricular premature beats, ventricular salvos, ventricular bigeminy, ventricular tachycardia (nonsustained and sustained), and we recorded the heart rate, systemic arterial blood pressure, and left ventricular function. Neither heart rate nor the number of ventricular arrhythmias differed significantly under baseline conditions. Conversely, the combined average number of ventricular ectopic beats during ischemia and reperfusion was significantly less in the presence of acetaminophen (28 +/- 4 vs. 6 +/- 1; P < 0.05). Similarly, percent ectopy during reperfusion in vehicle- and acetaminophen-treated dogs was 1.4 +/- 0.4 and 0.4 +/- 0.2, respectively (P < 0.05). The number of all ventricular ectopic beats except ventricular salvos was also significantly reduced in the presence of acetaminophen. Similar results were obtained with ouabain. Our results reveal that systemic administration of a therapeutic dose of acetaminophen has previously unreported antiarrhythmic effects in the dog.

Occupational exposures and squamous cell carcinoma of the oral cavity, pharynx, larynx, and oesophagus: a case-control study in Sweden.

OBJECTIVES: This community based case-referent study was initiated to investigate aetiological factors for squamous cell carcinoma of the upper gastrointestinal tract. METHODS: The study was based on all Swedish men aged 40-79 living in two regions of Sweden during 1988-90. Within that base, efforts were made to identify all incident cases of squamous cell carcinoma of the oral cavity, oropharynx and hypopharynx, larynx, and oesophagus. Referents were selected as a stratified (age, region) random sample of the base. The response was 90% among cases and 85% among referents. There were 545 cases and 641 referents in the final study group. The study subjects were interviewed about several lifestyle factors and a life history of occupations and work tasks. The exposure to 17 specific agents were coded by an occupational hygienist. The relative risk (RR) of cancer was calculated by logistic regression, standardising for age, geographical region, and alcohol and tobacco consumption. RESULTS: Exposure to asbestos was associated with an increased risk of laryngeal cancer, and a dose-response relation was present. The RR was 1.8 (95% confidence interval (95% CI) 1.1 to 3.0) in the highest exposure group. More than eight years of exposure to welding fumes was associated with an increased risk of pharyngeal cancer (RR 2.3 (1.1 to 4.7)), and laryngeal cancer (RR 2.0 (1.0 to 3.7)). There were indications of a dose-response for duration of exposure. Associations were also found for high exposure to polycyclic aromatic hydrocarbons (PAHs) and oesophageal cancer, RR 1.9 (1.1 to 3.2). Exposure to wood dust was associated with a decreased risk of cancer at the studied sites. CONCLUSIONS: Some of the present findings confirm known or suspected associations--such as asbestos and laryngeal cancer. The study indicates that welding may cause an increased risk of pharyngeal as well as laryngeal cancer. The findings corroborate an association between exposure to PAHs and oesophageal cancer.

Smoking tobacco, oral snuff, and alcohol in the etiology of squamous cell carcinoma of the head and neck: a population-based case-referent study in Sweden.

BACKGROUND: This case-referent study was conducted to elucidate the role of selected exogenous agents in the etiology of head and neck cancer. The factors studied were tobacco smoking, alcohol intake, the use of moist oral snuff, dietary factors, occupational exposures, and oral hygiene. In this first report, the authors discuss the impact of tobacco smoking, the use of oral snuff, and alcohol consumption. METHODS: The study base was approximately 2 million person-years at risk and consisted of Swedish males age 40-79 years living in 2 geographic regions during the years 1988-1990. A total of 605 cases were identified in the base, and 756 controls were selected by stratified random sampling from population registries covering the base. RESULTS: Among those who were tobacco smokers at the time of the study, the relative risk of head and neck cancer was 6.5% (95% confidence interval, 4.4-9.5%). After cessation of smoking, the risk gradually declined, and no excess risk was found after 20 years. The relative risk associated with alcohol consumption of 50 grams or more per day versus less than 10 grams per day was 5.5% (95% confidence interval, 3.1-9.6%). An almost multiplicative effect was found for tobacco smoking and alcohol consumption. CONCLUSIONS: Tobacco smoking and alcohol intake had a strong interactive effect on the risk of squamous cell carcinoma of the head and neck. Moderate alcohol intake (10-19 grams per day) had little or no effect among nonsmokers. No increased risk was found for the use of Swedish oral snuff.

Oral contraceptive use: interview data versus pharmacy records.

BACKGROUND: If women tend to forget and underreport their past oral contraceptive (OC) use, but the recall among cases is enhanced by the presence of disease, recall bias may explain some reported health effects of OC use. METHODS: Two different sources of information on lifetime OC use were compared for 427 (84%) of a community-based sample of 511 women aged 20-34: (i) structured interviews, using a life event calendar and picture display as memory aids, and (ii) a register of all prescriptions dispensed by pharmacies in the county since 1970. RESULTS: Interview data and pharmacy records showed high levels of agreement for any OC use, current use, time since first and last use, total duration of use, and for duration of use in different 'time windows'. But there was a tendency to under-report specific kinds of OC used in the past. CONCLUSION: Underreporting of OC use among non-cases would usually introduce little or no bias (as compared to pharmacy records) for this kind of interview and women. However, it may be preferable to use interviews for current OC use, and pharmacy records for specific kinds of OC used in the past.

PIP: In studies where women are interviewed about oral contraceptive (OC) use only after the emergence of disease (e.g., breast cancer), the experience of disease may enhance recall and reporting of OC use, resulting in overestimation of relative risks. This community-based study compared two sources of information on ever-use of OCs--structured interviews and pharmacy prescription records--in 427 women 20-34 years of age who were long-term residents of Sweden's Jamtland County where registration of prescriptions has been virtually complete since 1970. A life-events calendar and photographs of OCs in use since 1970 were used in the interviews to facilitate recall. 153 women reported current OC use; the pharmacy register failed to document a current prescription for 37 (24%). Only 4 (1.5%) of the 274 women who denied current OC use had an active prescription on file. Of the 37 women identified as never-users by interview, 2 (5%) had records of OC prescriptions (for under 2 years of use). Of the 36 women identified as never-users by pharmacy records, only 1 reported ever-use. Compared to the pharmacy registry, 13% reported a shorter and 28% a longer duration of OC use. Of women who reported OC use within 5 years of interview, 5-10 years earlier, and more than 10 years ago, 2.6% (8/312), 4.6% (14/307), and 12.8% (26/203), respectively, had no prescriptions on file for that time period. Discrepancies between the two data sources in time since first OC use were usually less than 2 years; the tendency was for women to overestimate rather than understate the actual duration of OC use. These findings suggest that interview data on OC use introduce minimal--if any--bias. Agreement between interviews and records in terms of the specific brands of OCs taken was less satisfactory. 19% of users of high-dose OCs, for example, did not recall the type of pill dispensed by the pharmacy. Thus, use of pharmacy records is recommended over interview data in studies where the specific OC formulation is of interest.

Retrospective versus original information on diet among cases of colorectal cancer and controls.

A cohort of subjects born 1908 to 1925 answered a questionnaire on dietary habits in 1967 (original information). Of the cases of colorectal cancer that were diagnosed in this cohort 1968-1983, 50 were still alive in 1987. A total of 150 controls were selected as a stratified (age, sex) random sample of those who did not have a colorectal cancer. In 1987, the cases and controls were asked to fill in a questionnaire on dietary habits in 1967 (retrospective information) as well as on their current dietary habits. The questions were identical and used to compare retrospective and original information on diet among cases and controls, taking into account any changes in dietary habits during the intervening period. Cases and controls usually had a similar tendency to overestimate or underestimate their previous food intake. For both cases and controls, the tendency to overestimate previous intake was closely related to an increase in consumption during the intervening period and vice versa. Among those subjects who had not altered their consumption during the intervening period, there was usually a rather good agreement between the retrospective and original information. This was true for the cases as well as for the controls. For certain food items, the results suggest that the use of retrospective information would introduce a differential misclassification. In order to avoid or reduce a differential misclassification introduced by differences between cases and controls in changes in consumption due to the disease under study, it may be advisable to interview the cases as soon as possible after diagnosis or even at the time of preliminary diagnosis.

Evaluation of a prescription based record-linkage model for epidemiological studies of long-term adverse effects of drugs--with special regard to combined oral contraceptives.

The Department of Drugs of the Swedish National Board of Health and Welfare undertook a study of the possibilities of a new scheme for post-marketing surveillance by means of prescription and register based epidemiological studies, primarily of combined oral contraceptives (COC). Based on available data on COC usage patterns and incidence rates of the disease at study, it was estimated that study periods, including the necessary time periods for disease development and generation of a sufficient number of cases, would amount to at least 1 to 13 years for cardiovascular outcomes and 8 to 17 years for reproductive cancers. Prospective and unbiased exposure ascertainment would be the most important advantage. However, delay in follow up, the need for extensive individual questionnaire probing and fear of violation of personal integrity could adversely affect the feasibility of the scheme. Chiefly on the grounds of the extended study periods and magnitude of the necessary infrastructure, it was not judged cost-effective to pursue such a scheme for COC exposure only. It was, however, suggested that it would be considered for epidemiological surveillance of other drugs that are commonly used and for which short term and frequent serious side effects are expected, as for instance lipid lowering compounds, beta-blockers, bensodiazepines and other psychotropic drugs.

Physical activity and colon cancer: a case-referent study in Stockholm.

A population-based case-referent study on physical activity (during working and recreational hours) and colon cancer was performed in Stockholm in 1986-1988. The study included 1,081 subjects. Low physical activity was associated with an excess risk of colon (but not rectum) cancer for both men and women, showing a dose-response relationship with decreasing levels of physical activity. The effect was seen in the left colon (relative risk = 3.2, 95% confidence interval = 1.5-7.0) rather than in the right colon (relative risk = 1.1, 0.5-2.5). These results persisted after adjustment for year of birth, gender, body mass, intake of total energy, protein, total fat, dietary fibre, and browned meat surface.

Diet, body mass and colorectal cancer: a case-referent study in Stockholm.

A population-based case-referent study on diet (total energy, protein, fat, dietary fiber), body mass and colorectal cancer was performed in Stockholm in 1986-1988. The study included 1,081 subjects. The relative risks (RR, with a 95% confidence interval, highest versus lowest quintile) for colon cancer were as follows: total energy (1.7, 1.0-3.0), protein (2.4, 1.5-4.0), total fat (2.2, 1.3-3.6), dietary fiber for men (0.5, 0.2-1.1), dietary fiber for women (1.2, 0.7-2.3) and body mass (2.0, 1.3-3.1). The relative risks for rectal cancer were: total energy (2.4, 1.2-4.7), protein (3.6, 2.0-6.4), total fat (2.5, 1.4-4.6), dietary fiber (0.5, 0.3-0.9), body mass for men (1.7, 0.7-4.0), and body mass for women (1.0, 0.5-1.9). Adjustment for physical activity, body mass (in the diet analysis), the above-mentioned dietary factors (in the body mass analysis), and browned meat surface had little or no influence on the results.

Retrospective versus original information on diet: implications for epidemiological studies.

The aim of this study was to evaluate the use of retrospective information on diet in relation to the information originally reported. Hospital controls (n = 131) who participated in a case-control study on diet and pancreatic cancer in Stockholm, Sweden, answered a second postal questionnaire four years later about their current and previous food consumption. The food consumption was dichotomized for the purpose of the analysis. In relation to the original information, the use of retrospective information overestimated previous food consumption among subjects with increased intake, while retrospective information underestimated previous food consumption among subjects with decreased intake. These tendencies were slightly more pronounced in the age group 60-79 years than in the age group 40-59 years. For subjects with unchanged food consumption, there was a high agreement between original and retrospective information. Considerable differential misclassification could be introduced in an epidemiological study if cases and non-cases differ with regard to changes in food consumption.

Vitamin A supplements, fried foods, fat and urothelial cancer. A case-referent study in Stockholm in 1985-87.

In a population-based case-referent study of urothelial cancer in Stockholm during 1985-87, information was obtained from 78% of 418 identified cases and 77% of 511 selected referents. The relative risk (with 95% confidence interval) for intake of vitamin A supplements was 0.5 (0.2-1.0), with a dose-response relationship with increasing frequency of consumption. Increased risks of urothelial cancer were seen for several fried foods, for example fried meat [relative risk 1.4 (1.0-1.8) for weekly intake] and fried potatoes [relative risk 1.6 (1.1-2.6) for weekly intake]. Subjects with a high intake of fried foods, as defined by a collapsed variable, had a relative risk of 2.4 (1.4-4.2). A dose-response relationship was also seen with an increasing average daily intake of fat [relative risk 1.7 (1.0-2.8) in the highest quintile], but adjusting for fried foods decreased the relative risk, and it is uncertain whether the adjustment allowed for residual confounding. No association was noted for meat other than fried, but the analysis was based on small numbers.

Increased risk of urothelial cancer in Stockholm during 1985-87 after exposure to benzene and exhausts.

In a population-based case-referent study of urothelial cancer in Stockholm during 1985-87, information was obtained from 80% of 320 identified male cases and 79% of 363 selected male referents. Industrial exposures were assessed for each subject by an industrial hygienist on the basis of questionnaire data. Exposure to benzene (any annual dose) gave a relative risk (with 95% confidence interval) of 2.0 (1.0-3.8). The highest risk was seen for a high annual dose. Subjects exposed to both diesel and petrol exhausts (moderate/high annual dose) had a relative risk of 7.1 (0.9-58.8). However, adjusting for benzene changed the relative risk to 5.1 (0.6-43.6). It might be rewarding to consider whether benzene from petrol confounds the associations previously suggested between exhausts and urothelial cancer. Exposure to polychlorinated biphenyls (PCB) gave a relative risk of 3.3 (0.6-18.4).

An extended family with a dominantly inherited speech disorder.

A three-generation family is described in which 16 members have a severe developmental verbal dyspraxia. Inheritance is autosomal dominant, with full penetrance. Intelligence and hearing are normal.

Colorectal cancer in Sweden. A descriptive epidemiologic study.

In a register-based 19-year follow-up we studied the incidence rate of colorectal cancer in the Swedish 1960 census population. A total of 53,377 cases were identified: 28,003 men and 25,374 women. A U-shaped distribution of tumors in the large bowel was observed, with a minimum in the descending colon. Other findings were 1) An incidence gap between elderly men and women increasing with age and with distal direction in the large bowel; 2) An increase in the incidence of colorectal cancer with population density; 3) A higher incidence of colorectal cancer in the southwestern region than in the northern region and 4) A lower incidence of colon cancer among blue than among white collar workers and a lower incidence of colorectal cancer among never married men than among other men.

Malignant melanoma: aetiological importance of individual pigmentation and sun exposure.

A case-control study of cutaneous malignant melanoma (CMM) was based on 523 incident cases and 505 age- and sex-matched controls selected from the general population. The purpose was to investigate the relative risk of developing CMM associated with different sun habits and indicators of pigmentation, such as skin type, eye colour and hair colour. Compared to people with black hair, blonde subjects had a relative risk of 74.4 (95% confidence interval, 45.8-120.8). Associations with skin type and eye colour were considerably weaker. Relative risks of about 1.5-2.5 were found for certain sun habits. The results suggest that in a population of Caucasian origin with a predominantly fair complexion, pigmentary status characterized by hair colour is a far more important aetiological factor than sun habits.

Urothelial cancer and some industry-related chemicals: an evaluation of the epidemiologic literature.

In a previous cohort study by our group, certain industry-related chemicals were judged as warranting further attention as possible urothelial carcinogens. In this paper, the epidemiologic literature of cancer of the lower urinary tract is evaluated for these substances. We would like to add combustion gases/soot from coal to the substances considered as increasing the risk of urothelial cancer. It is, however, uncertain whether this risk is due to contaminants of aromatic amines in tar volatiles or whether it depends on other agents, such as nitroarenes or polycyclic aromatic hydrocarbons. Furthermore, we find some support for the hypothesis that exposure to chlorinated aliphatic hydrocarbons increases the risk of urothelial cancer. For creosote, cutting fluids and cutting oils, hair dyes, and polychlorinated biphenyls, data are scarce. Available data do not support the hypothesis that asbestos is associated with urothelial cancer. "Publication bias," such that only limited information was available, was judged to be a potential problem in the review for many, but not all, of the substances investigated.

Retrospective versus original information on cigarette smoking. Implications for epidemiologic studies.

This study was conducted to evaluate the agreement between retrospective information on cigarette smoking and original information obtained six years previously. A questionnaire on smoking habits was answered by 94% of a random sample of the adult Swedish population in 1963 (original information). Of the 10,356 subjects aged 40-59 years who reported that they had ever smoked regularly, 9,394 answered a second questionnaire in 1969. Information was obtained on present smoking habits as well as on smoking habits in 1963 (retrospective information). Cigarette consumption was divided into four categories: 0, 1-7, 8-15, and 16+ cigarettes per day. In relation to the original information on smoking, retrospective information showed a strong tendency to overestimate previous cigarette consumption among subjects who had increased their cigarette smoking (69%), and to underestimate previous cigarette consumption among subjects who had decreased their cigarette smoking (49%). Subjects with unchanged cigarette consumption showed a high level of agreement between original and retrospective information (89%). Age, sex, income, and occupational status also had some impact on the agreement between retrospective and original information on cigarette consumption. Consequences for epidemiologic studies based on retrospective smoking information are discussed. The use of retrospective information may introduce considerable differential misclassification when cases and noncases differ with regard to changes in smoking habits.

Mortality and social class in Sweden--exploring a new epidemiological tool.

Total mortality, mortality from coronary heart disease (CHD), cerebrovascular disease, and other causes of death, were examined for three social groups and ten socio-economic groups in Sweden. The study included all subjects born in the country between 1896 and 1940 who were economically active in 1960-1.9 million men and 0.7 million women. Information on social and socio-economic status, and other social and demographic characteristics, was obtained from the 1960 Census. Information on cause-specific mortality during the period 1961-68 was obtained from a record linkage with the Cause of Death Registry. The analyses were based on 112,469 deaths and 21 million person years at risk. Information on smoking habits was obtained from a sample of 55,000 from the Census population. CHD mortality for women was high among manual workers, SMR = 110 (95% confidence limits 104-117), and low among non-manual workers, SMR = 84 (78-91). CNS-vascular mortality for women was also high among manual workers, SMR = 107 (110-115), and low among non-manual workers, SMR = 89 (82-97). Heavy smoking was more common among non-manual workers in both sexes, which may have contributed to a reverse social class gradient among men, with non-manual male workers being at higher risk for CHD than manual male workers. Farmers (and agricultural workers) generally had a low mortality. Other self-employed men and women had a high total mortality, a high mortality from CHD and CNS-vascular disease--and a high proportion of heavy smokers. There remain differences in mortality between social and socio-economic groups which cannot be explained by smoking habits, age, gender, urbanization, region of residence and martial status.

Industry-related urothelial carcinogens: application of a job-exposure matrix to census data.

A job-exposure matrix has been developed linking the work tasks in the Swedish National Census of population 1960 to exposure to 50 single agents or groups of substances. All 1,905,660 men, aged 20-64 years in 1960, reporting themselves as gainfully employed in the Census, were observed for the occurrence of urothelial cancer 1961-1979 by linkage to the National Swedish Cancer Registry. Subjects classified as exposed to creosote had a relative risk (with 95% confidence interval) of 2.6 (1.2-5.9) for renal pelvis cancer and 1.3 (1.0-1.8) for urinary bladder cancer; subjects exposed to polychlorinated biphenyls (PCB) had a relative risk of 1.3 (1.0-1.8) for urinary bladder cancer. Adjustment was made for age, socioeconomic group, and degree of urbanization. Exposure to combustion gases from coal gave a relative risk of 1.2 (1.0-1.4) for bladder cancer. The study carries several sources of nondifferential misclassification diluting the estimates of the relative risks toward 1.0. The limitations of exposure classification by job-exposure matrices are discussed.

Physical activity and colon cancer risk.

The association between low physical activity and colon cancer was examined in a Swedish 14-year follow-up study of 16,477 subjects. The relative risk (RR) of colon cancer in subjects with low physical activity was estimated at 3.6 (1.3-9.8, 95% confidence interval). An association was observed for both men and women, and for low physical activity during occupational hours (RR = 1.6, 0.8-2.9) as well as during recreational hours (RR = 1.6, 1.0-2.7). The relative risk for rectal cancer was not elevated. In the study we controlled for age, gender, domicile and, to some extent, for diet. A possible mechanism is that low physical activity could prolong the transit time of the stool in the colon and thereby the duration of contact between the mucosa and fecal carcinogens.