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Biomedical subjects

H Becher

Publications and source records attributed to H Becher.

At least 109 records · Page 6Linked to original sources

[The importance of genetic factors for development of breast cancer].

It is well documented that breast cancer aggregates in certain families suggesting a genetic etiology for this cancer. Numerous epidemiologic studies have shown that women with a first degree relative (mother, sister) with breast cancer have double the risk of developing this cancer when compared to women in the general population. More recent studies have shown that the magnitude of the risk of developing breast cancer is dependent on the age at diagnosis and the number of relatives affected. Aggregation of breast cancer in families in itself does not clarify the true nature of the underlying factors which could be genetic or due to familial resemblance in other risk factors. Complex segregation analyses of breast cancer families suggest that breast cancer susceptibility is inherited in some families as an autosomal dominant trait. Recently, a breast cancer susceptibility gene, BRCA1, has been mapped to chromosome 17q12-q21 through linkage analyses. BRCA1 appears to play a role in families with a large number of breast cancer cases who have developed breast cancer before the age 45, and/or who have breast and ovarian cancer cases. The risk of cancer for female carriers of the BRCA1 mutation has been estimated to be 87% for breast cancer and 44% for ovarian cancer by the age of 70. BRCA1 seems to play a role in only a proportion of affected families and it is likely that other genes are also involved. In the majority of breast cancer families with two or three cases, BRCA1 appears to play a small role.

Adult↗

Efficacy SH U 508 A (Levovist) as blood pool enhancer in the Doppler evaluation of multiple vascular regions.

SH U 508 A (Levovist) as a blood pool enhancer to investigate multiple vascular regions with Doppler ultrasonography. Thirty patients with sub-optimal cardiac or peripheral vascular Doppler exams received 75 intravenous contrast bolus injections in all to investigate the intensity and the duration of Doppler signal enhancement after the i.v. administration of an echo contrast agent - i.e., SH U 508 A (Levovist) by Schering AG, Berlin, Germany. All cases exhibited Doppler enhancement and the investigator's "diagnostic confidence" increased from 35% (precontrast) to 91% (post-contrast) (p < 0.05). Audio Doppler intensity was measured quantitatively and more than 16 dB enhancement was demonstrated in all the vascular regions under investigation (p < 0.05). Enhancement lasted more than 60 seconds in the peripheral vessels and 120 seconds in the heart vessels. No clinically relevant adverse reactions were ever observed. To conclude, i.v., -administered SH U 508 A (Levovist) is a valuable means of increasing cardiac, femoral arterial and transcranial (cerebral arterial) Doppler signal intensity. Enhancement is durable and improves the clinical diagnostic confidence in the patients with suboptimal Doppler findings.

Adult↗

Chemical exposure in manufacture of phenoxy herbicides and chlorophenols and in spraying of phenoxy herbicides.

Exposure patterns are reported for manufacturing and sprayer cohorts incorporated in the "IARC International Register of Workers exposed to Phenoxy Herbicides and Contaminants." Information was based on company questionnaires, company reports, plant visits, and serum 2, 3, 7, 8-TCDD measurements. In addition to phenoxy herbicides and chlorophenols, workers in manufacturing plants may have been exposed to raw materials, process chemicals, other agents synthesized or formulated, and impurities of all these agents. Sprayers also had a complex exposure pattern, including phenoxy herbicides and some other pesticides, their carriers and additives, and residues of chemicals formed during manufacture. Occurrence of agents, including dioxins, varied between countries. Biological monitoring and industrial hygiene data were rarely available, most since the late 1970s. Exposure of workers depended mainly on the jobs they performed, but several factors influenced level of exposure. A quantitative exposure classification is not feasible in this study. Semiquantitative exposure estimates may be derived through a critical interpretation of biological monitoring and industrial hygiene data together with individual work histories.

2-Methyl-4-chlorophenoxyacetic Acid↗

Enhancement of mitral regurgitation and normal left atrial color Doppler flow signals with peripheral venous injection of a saccharide-based contrast agent.

OBJECTIVES: The saccharide ultrasound contrast agent SHU 508 A was used to test the hypothesis that an intravenous, transpulmonary contrast method can enhance color Doppler flow signals in the left atrium in a clinically useful manner. BACKGROUND: Color Doppler display of mitral regurgitation may be unreliable because of variable signal to noise ratios that are at times poor. Traditional contrast agents enhance color Doppler flow signals in the right heart chambers. This study describes our observation of a recently developed contrast agent, SHU 508 A, capable of pulmonary transit after peripheral venous injection. METHODS: Control subjects (n = 10) and patients with suspected mitral regurgitation (n = 23) were studied by color Doppler flow imaging before and after 3-g intravenous doses of SHU 508 A. Reference grading of mitral regurgitation (0 to 3) was formulated from left ventricular angiography. In the four-chamber view of the left atrium, we selected for analysis the systolic frame with the maximal retrograde jet of mitral regurgitation (aliased/blue) and the diastolic frame with the maximal color coding from anterograde pulmonary venous flow (red) for planimetry and for grading the intensity of the color Doppler signal (0 to 5). RESULTS: The score of the color Doppler signal intensity increased by > or = 2.5 after 3 g of SHU 508 A (p < 0.001). Flow detection improved, as shown by the increased jet area of mitral regurgitation (> or = 170%), after 3 g of SHU 508 A (3 +/- 3 vs. 12 +/- 8 cm2, p < 0.001) and by a > or = 200% increase in normal anterograde flow area (p < 0.001) in both the mitral regurgitation group and the control group. After contrast enhancement, the correlation between angiographic grading and the relation of jet area to the left atrial area increased from r = 0.79 to r = 0.91. CONCLUSIONS: Contrast-mediated increased echogenicity of the left atrial blood pool improves the signal to noise ratio of Doppler images of mitral regurgitation and anterograde atrial flow. The technique is safe and simple and seems to minimize variability due to instrument design and anatomic signal attenuation.

Adult↗

Effect of occupational air pollutants on various histological types of lung cancer: a population based case-control study.

A population based case-control study was performed in Cracow, Poland, to determine the effect of occupational air pollutants on various histological types of lung cancer. Male cases and controls were identified from the Cracow Death Register. Information was obtained by mailed questionnaire from next of kin on smoking, occupational branch, occupational exposures, and other pertinent variables. Response rates were 73.5% in cases and 72.0% in controls. For cases that underwent a bronchial biopsy or surgical excision the histological diagnosis of the tumour was obtained from clinical records. The case group contained 343 subjects with squamous cell carcinomas, 151 with small cell carcinomas, and 106 with adenocarcinomas. Twenty seven cases showed other histological types (large cell carcinoma and not classifiable). Analysis was performed separately by histological type for occupational exposure variables adjusted for smoking. Long term exposure to mineral dust and metal dust (20 years or more) was found to be a significant risk factor for small cell and squamous cell carcinoma. The effect was more pronounced if the analysis was restricted to those aged less than 70 years. The highest relative risk (RR) due to occupational exposures was found for squamous cell carcinoma and exposure to mineral dust for more than 20 years (RR = 2.45, 95% CI 1.43-4.19). The estimated effect of mineral dust on small cell carcinoma and adenocarcinoma was smaller (RR = 2.29, 95% CI 1.16-4.53 and RR = 2.04, 95% CI 0.89-4.64 respectively). The effect of metal dust and fumes seemed about the same for squamous and small cell carcinoma. No specific agent could be identified as particularly important for a specific histological type; it rather seemed that the effects of the substances considered were similar for lung cancers in general.

Adenocarcinoma↗

The concept of residual confounding in regression models and some applications.

In this paper the concept of residual confounding is generalized to various types of regression models such as logistic regression or Cox regression. Residual confounding and a newly suggested parameter, the relative residual confounding, are defined on the regression parameters of the models. The estimator gives the proportion of confounding which has been removed by incomplete adjustment. The concept quantifies the effects of categorizing continuous covariables and of model misspecification. These are investigated by a simulation study and with data from an epidemiological investigation. A case-control study of laryngeal cancer is used to illustrate the residual confounding effect of arbitrary transformation of a continuous confounder, smoking, on the effect of alcohol consumption on laryngeal cancer risk. The data also showed that categorization into two levels can yield high residual confounding. The parameters described in this paper are of some use in quantifying the effect of inadequate adjustment for confounding variables.

Alcohol Drinking↗

Effect of tobacco smoking on various histological types of lung cancer.

In a population-based case/control study the differential lung cancer risk patterns due to tobacco smoking habits of various histological types have been investigated. The cases were 1432 deaths from lung cancer in the years 1980-1987, of which the histological type was known for 627 individuals. There was 54% squamous cell carcinoma, 24% small-cell carcinoma and 17% adenocarcinoma. Controls were 1343 deaths from other causes. Next-of-kin interviews were performed. The results of the study confirmed that cigarette smoking is associated with all histological types of lung cancer; however, the dose/response relationship between smoking and adenocarcinoma differed clearly from that observed in squamous and small-cell carcinomas. In the latter histological types the gradient of risk was much stronger as the number of cigarettes smoked or duration of smoking increased. The overall relative risk for smoking in small-cell and squamous cell carcinoma was 15.4 and 13.5 respectively, whereas that for adenocarcinoma was weaker (relative risk = 3.1). An interesting difference between squamous and small-cell carcinomas was found also for patients who gave up smoking. The effect of stopping was more pronounced in squamous cell carcinoma. The attributable risks for smoking in squamous and small-cell carcinoma were much higher (90% and 88% respectively) than for adenocarcinoma (64%). The data suggest that adenocarcinoma is likely to be related to other factors than tobacco smoking to a greater extent than are squamous or small cell carcinoma. Possible sources of bias, such as missing histological diagnoses, are discussed in detail.

Adenocarcinoma↗

Occupational and environmental hazards associated with lung cancer.

In a hospital-based case-control study 194 lung cancer cases, 194 hospital controls, and 194 population controls were interviewed for their smoking, occupational, and residential history by trained interviewers, using a standardized questionnaire. In order to include many different environmental exposures, case ascertainment took place in seven different hospitals with catchment areas ranging from rural to highly industrialized. Lung cancer risk strongly increases with cumulative cigarette dose, reaching an odds ratio (OR) of 16.19 (95% confidence limits (CL): 5.10, 51.33) for male smokers of more than 40 pack-years and an OR of 19.99 (95% CL: 4.98, 80.24) for female smokers of more than 20 pack-years. For the quantification of occupational exposure to known carcinogens of the lung a novel approach was developed which accumulates exposure information obtained by supplemental questionnaires through an automatic procedure. The OR for the highest exposure group in males was 2.7 (95% CL: 1.23, 5.78). Significantly increased risks were observed in the metal industry, particularly in smelter and foundry workers (OR 4.8, 95% CL: 1.15, 20.16) and in turners (OR 2.2, 95% CL: 1.05, 4.75). In the construction industry the risks were particularly high in road construction workers (OR 3.7, 95% CL: 1.06, 13.20) and in unskilled construction workers (OR 2.7, 95% CL: 1.24, 5.76). The risks in these occupational groups increased with duration and with latency. Quantification of air pollution was done on a county basis by time period. An index based on emission data for sulphur dioxide was compared to a semiquantitative index, which included additional information on ambient air pollution. After adjustment for smoking and occupational exposures an OR of 1.01 (95% CL: 0.53, 1.91) for an emission index and of 1.16 (95% CL: 0.64, 2.13) for a semiquantitative index was obtained.

Adult↗

Passive smoking in Germany and Poland: comparison of exposure levels, sources of exposure, validity, and perception.

Nonsmoking females age 35-65 years from Bremen, Germany (91 women), and Opole, Poland (98 women), were interviewed about their recent passive smoking exposure. We obtained urine samples at the time of interview and determined the concentration of cotinine as an indicator of tobacco smoke exposure. In Poland and in Germany, the vast majority of nonsmoking women are involuntarily exposed to environmental tobacco smoke (ETS). Polish women had slightly higher exposure levels than German women, with overall means of 9.93 and 8.65 ng cotinine/mg creatinine, respectively. Smoking by the husband was the major source of exposure in both study groups. In the Polish group, the work place was also an important source of ETS exposure. The validity of self-reported passive smoking exposure was found to be generally good; it was somewhat better in the German study group. A negative attitude toward tobacco smoke was slightly stronger among the German women. The percentage of women misreporting their active smoking status was low.

Adult↗

[Effect of smoking on the development of various histological types of lung cancer].

The aim of this clinically controlled trial was to assess the effect of different smoking patterns on development of different histological types of lung cancer. The study group consisted of 1,432 subjects that died due to lung cancer in the years 1980-1987. 627 of these had the histological type of the cancer determined; 54% had squamous cell cancer, 24% small cell lung cancer (SCLC), 17% adenocarcinoma. The control group consisted of 1,343 subjects that died due to other causes. Medical and social history was taken from the families of the deceased. The results of the analysis demonstrate that lung cancer development is related to smoking although differences were seen in the different types of cancer. The calculated risk of a smoker developing lung cancer-squamous cell and SCLC was respectively 15.4 and 13.5 while for adenocarcinoma it was much lower--3.1. Important differences were seen in ex-smokers developing squamous cell lung cancer and SCLC. The risk of developing squamous cell lung cancer and SCLC in this group was 89% and 88%, and adenocarcinoma only 64%. This suggests that adenocarcinoma is related more to environmental factors than the other two types of lung cancer.

Adenocarcinoma↗

Alternative parameterization of polychotomous models: theory and application to matched case-control studies.

A method is proposed for transforming a class of models having an outcome variable with more than two levels into an equivalent binary model. The polychotomous logistic model is used to demonstrate the method. The equivalency to a simple logistic regression model after some data transformation (augmentation) is shown. The method is applied to the data from two case-control studies each with two control groups, and further applications are indicated.

Breast Neoplasms↗

Tobacco, alcohol, and diet in the etiology of laryngeal cancer: a population-based case-control study.

Cancer of the larynx constitutes an increasingly important problem in Polish males during the last 25 years. A population-based case-control study of laryngeal cancer among people under 65 years of age was conducted in Lower Silesia, a province in Southwest Poland, from 1986 to 1987, with 249 newly-diagnosed cancer cases and 965 controls. The estimated relative risk (RR) for smoking and alcohol are both very high: for smoking more than 30 cigarettes, RR = 59.7 (95 percent confidence interval [CI]: 13.0-274); for drinking vodka regularly for more than 30 years, RR = 10.4 (95 percent CI: 4.0-27.2). Exposures to alcohol and tobacco show a clear multiplicative effect in all categories of exposure. The risk was shown to be reduced by quitting smoking (RR = 0.3, 95 percent CI: 0.14-0.64, after 10 years) or by having a history of intermittent smoking. Poor nutrition was also identified as a strong independent risk factor. However, data quality regarding this factor is not as high as for tobacco and alcohol. Smoking alone accounts in this study for an estimated 95.2 percent of all the cases of laryngeal cancer.

Adult↗

Smoking cessation and nonsmoking intervals: effect of different smoking patterns on lung cancer risk.

A case-control study of lung cancer was conducted in northwestern Germany in 1985-86. The study included 194 lung cancer cases and the same number of hospital controls and population controls who were matched to the cases by sex and age. Personal interviews were conducted by trained interviewers. We report here the effect of different smoking patterns--such as nonsmoking intervals, and time since quitting smoking--on lung cancer risk. Both quitting smoking and having a nonsmoking interval are seen to reduce lung cancer risk significantly. For a nonsmoking interval of three years or more, relative risk (RR) = 0.21, 95 percent confidence interval (CI) = 0.08-0.52; for quitting smoking for 10 years or more, RR = 0.23, CI = 0.11-0.48). A dose-response relationship was estimated for cigarette dose, length of nonsmoking interval, and time since stopped smoking.

Adult↗

Adjusting for misselection using subsampling in epidemiological studies.

In epidemiological research it is sometimes necessary to conduct a case-control study in a part of the population which is not exposed to certain risk factors. Such a study design may be useful to investigate the risk related to a weak carcinogen in presence of other strong risk factors. It may happen that some individuals are wrongly included in the study group due to misreporting of the true exposure status. This misselection may cause biased odds ratio estimates of the factors of interest. It is therefore recommended that an evaluation study to validate the selection procedure is undertaken. We propose a two-stage sample design, consisting of a case-control study and a validation study in a subsample. Misselection rates in cases and control for different exposure groups may be estimated in the subsample and used to correct the odds ratio estimation from the first stage. It is shown how the total sample size should be attributed to the case-control sample and to the second-stage sample in order to give an unbiased estimate with minimal variance. The allocation is shown to be dependent on a number of parameters which is illustrated numerically and graphically. Efficiency considerations are also addressed.

Case-Control Studies↗

Exposure of nonsmoking women to environmental tobacco smoke: a 10-country collaborative study.

The interpretation and interpretability of epidemiologic studies of environmental tobacco smoke (ETS) depend largely on the validity of self-reported exposure. To investigate to what extent questionnaires can indicate exposure levels to ETS, an international study was conducted in 13 centers located in 10 countries, and 1,369 nonsmoking women were interviewed. The present paper describes the results of the analysis of self-reported recent exposure to ETS from any source in relation to urinary concentrations of cotinine. Of the total, 19.7 percent of the subjects had nondetectable cotinine levels, the median value was 6 ng/mg, and the cut-point of the highest decile was 24 ng/mg. The proportion of subjects misreporting their active smoking habit was estimated at between 1.9 and 3.4 percent, depending on whether cut-points of 50 or 100 ng/mg creatinine were used. Large and statistically significant differences were observed between centers, with the lowest values in Honolulu, Shanghai, and Chandigarh, and the highest in Trieste, Los Angeles, and Athens. Mean cotinine/creatinine levels showed a clear linear increase from the group of women not exposed either at home or at work, to the group of those exposed both at home and at work. Values were significantly higher for women exposed to ETS from the husband but not at work, than for those exposed at work but not from the husband. The results of linear regression analysis indicated that duration of exposure and number of cigarettes to which the subject reported being exposed were strongly related to urinary cotinine. ETS exposure from the husband was best measured by the number of cigarettes, while exposure at work was more strongly related to duration of exposure. After adjustment of number of cigarettes for volume of indoor places, a similar increase in cotinine (5 ng/mg) was predicted by the exposure to 7.2 cigarettes/8 h/40 m3 from the husband and 17.9 cigarettes/8 h/40 m3 at work. The results indicate that, when appropriately questioned, nonsmoking women can provide a reasonably accurate description of ETS exposure. Assessment of individual exposure to ETS should focus on daily duration and volume of indoor places where exposure occurred.

Adult↗

A case-control study of lung cancer with special reference to the effect of air pollution in Poland.

STUDY OBJECTIVE: The aim of the study was to assess the affect of inhaled pollutants on lung cancer risk. DESIGN: The study was a retrospective case-control survey of lung cancer deaths over a six year period (1980-1985). Information on occupation, smoking habits, and residency was collected from next of kin. Classification of exposure to community air pollution was based on measured levels of total suspended particular matter and sulphur dioxide. SETTING: Cases and controls had been resident in the city of Cracow, Poland. PARTICIPANTS: Cases were male (n = 901, questionnaire response rate 70.7%) and female (n = 198, response rate 65.1%) lung cancer deaths; controls were deaths from other causes, excluding other respiratory diseases, and frequency matched by age and sex (males n = 875, response rate 73.5%; females n = 198, response rate 64.0%). MAIN RESULTS: Lung cancer risk was found to depend strongly on total cigarette consumption, on age at starting to smoke, and on time since stopping smoking. Relative risk estimates for occupational exposure in iron and steel foundries or in other industries were significantly increased in males. Relative risk in men for highest air pollution level was 1.48 (95% confidence interval 1.08-2.01), while in women the increase was not significant. The joint action of the risk facts of smoking, occupational exposure, and air pollution was found to fit almost perfectly into a multiplicative model. CONCLUSIONS: Under conditions found in Cracow, air pollution may increase lung cancer risk, acting multiplicatively with known risk factors such as smoking and industrial exposure.

Adolescent↗