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W Schill

Publications and source records attributed to W Schill.

At least 19 recordsLinked to original sources

Minmax designs for planning the second phase in a two-phase case-control study.

Two-phase designs, in which a subsample with validation or complete information data is sampled stratified both on outcome and covariate from a first-phase study with incomplete data, have been proposed over 10 years ago and have been proven to result in efficient estimates with respect to standard designs. The efficiency depends, however, on the sampling fractions within each stratum. Our aim is to present a strategy for obtaining an optimized design, i.e. sampling fractions, that makes use of available phase-one data of an existing case-control study considered as the first-phase sample when the focus is on estimating a parameter vector. No global optimal design exists and local optimal designs depend on scenarios comprising the true disease model and the association between the phase-one and phase-two information. We develop an admissibility test that rejects scenarios inconsistent with the phase-one data and, for the selected scenarios, determine a minmax D- or A-optimal design that protects against worst-case scenarios. This work is applied on two examples.

Asbestos↗

Asbestos fibreyears and lung cancer: a two phase case-control study with expert exposure assessment.

AIMS: To assess the cumulative effect of asbestos on lung cancer risk where the exposure is assessed by an expert rating. METHODS: 1678 male cases and controls were enrolled in a population based matched case-control study, focused on occupational risk factors, carried out in West Germany. The exposure to asbestos was computed as lifelong working hours. For a validation subsample of 164 matched pairs from this study the intensity of asbestos exposure was further assessed by a panel of experts in order to obtain an estimate of the cumulative exposure on a time by intensity scale (fibreyears). The information on duration of asbestos exposure in the original study was combined with the fibreyears following the two phase case control study paradigm. RESULTS: The number of exposed subjects in the validation subsample was 75 cases and 71 controls. The percentage of subjects with a cumulative exposure < or =1, 1 to < or =10, and >10 fibreyears was 16%, 15%, and 15% for the cases and 18%, 16%, and 9% respectively for the controls. The smoking adjusted odds ratios for the fibreyears based on an unconditional logistic regression were 0.81, 1.02, and 1.60 respectively with increasing exposure categories (not significant). The coefficient (beta) for a log transformed trend was 1.156. Applying the two phase paradigm, these odds ratios became 0.86, 1.33, and 1.94; the latter reached significance and the beta coefficient was 1.178. CONCLUSIONS: The two phase paradigm allowed us to obtain a more precise estimate of the effect of asbestos on lung cancer. Results are consistent with a doubling of the lung cancer risk with 25 fibreyears asbestos exposure.

Adult↗

The contribution of cigarette smoking to bladder cancer in women (pooled European data).

BACKGROUND: Using a combined analysis of 11 case-control studies from Europe, we have investigated the relationship between cigarette smoking and bladder cancer in women. METHODS: Available smoking information on 685 female bladder cancer cases and 2416 female controls included duration of smoking habit, number of cigarettes smoked per day, and time since cessation of smoking habit for ex-smokers. RESULTS: There was an increasing risk of bladder cancer with increasing duration of smoking, ranging from approximately a two-fold increased risk for a duration of less than 10 years (odds ratio (OR) = 1.9, 95% confidence interval (CI) 1.1-3.1) to over a four-fold increased risk for a duration of greater than 40 years (OR = 4.1, 95% CI 3.0-5.5). A dose-response relationship was observed between number of cigarettes smoked per day and bladder cancer up to a threshold limit of 15-20 cigarettes per day, OR = 3.8 (95% CI 2.7-5.4), after which no increased risk was observed. An immediate decrease in risk of bladder cancer was observed for those who gave up smoking. This decrease was over 30% in the immediate 1-4 years after cessation, OR = 0.68 (95% CI 0.38-1.2). However, even after 25 years the decrease in risk did not reach the level of the never-smokers, OR = 0.27 (95% CI 0.21-0.35). CONCLUSION: The proportion of bladder cancer cases among women attributable to ever smoking was 0.30, (0.25-0.35) and to current smoking was 0.18 (0.14-0.22). These attributable proportions are less than those observed among men, although they are likely to increase in the future as the smoking-related disease epidemic among women matures.

Adult↗

Cigarette smoking and bladder cancer in men: a pooled analysis of 11 case-control studies.

The primary risk factor for bladder cancer is cigarette smoking. Using a combined analysis of 11 case-control studies, we have accurately measured the relationship between cigarette smoking and bladder cancer in men. Available smoking information on 2,600 male bladder cancer cases and 5,524 male controls included duration of smoking habit, number of cigarettes smoked per day and time since cessation of smoking habit for ex-smokers. There was a linear increasing risk of bladder cancer with increasing duration of smoking, ranging from an odds ratio (OR) of 1.96 after 20 years of smoking (95% confidence interval [CI] 1.48-2.61) to 5.57 after 60 years (CI 4.18-7.44). A dose relationship was observed between number of cigarettes smoked per day and bladder cancer up to a threshold limit of 15-20 cigarettes per day, OR = 4.50 (CI 3.81-5. 33), after which no increased risk was observed. An immediate decrease in risk of bladder cancer was observed for those who gave up smoking. This decrease was over 30% after 1-4 years, OR = 0.65 (0. 53-0.79), and was over 60% after 25 years of cessation, OR = 0.37 (0. 30-0.45). However, even after 25 years, the decrease in risk did not reach the level of the never-smokers, OR = 0.20. (0.17-0.24). The proportion of bladder cancer cases attributable to ever-smoking was 0.66 (0.61-0.70) for all men and 0.73 (0.66-0.79) for men younger than 60. These estimates are higher than previously calculated.

Adult↗

Occupational risk factors for urothelial carcinoma: agent-specific results from a case-control study in Germany. MURC Study Group. Multicenter Urothelial and Renal Cancer.

BACKGROUND: This multicentre population-based case-control study was conducted to estimate the urothelial cancer risk for occupational exposure to aromatic amines, polycyclic aromatic hydrocarbons (PAH), and chlorinated hydrocarbons besides other suspected risk factors. METHODS: In a population-based multicentre study, 1035 incident urothelial cancer cases and 4298 controls matched for region, sex, and age were interviewed between 1991 and 1995 for their occupational history and lifestyle habits. Exposure to the agents under study was self-assessed as well as expert-rated with two job-exposure matrices and a job task-exposure matrix. Conditional logistic regression was used to calculate smoking adjusted odds ratios (OR) and to control for study centre and age. RESULTS: Urothelial cancer risk following exposure to aromatic amines was only slightly elevated. Among males, substantial exposures to PAH as well as to chlorinated solvents and their corresponding occupational settings were associated with significantly elevated risks after adjustment for smoking (PAH exposure, assessed with a job-exposure matrix: OR = 1.6, 95% CI: 1.1-2.3, exposure to chlorinated solvents, assessed with a job task-exposure matrix: OR = 1.8, 95% CI: 1.2-2.6). Metal degreasing showed an elevated urothelial cancer risk among males (OR = 2.3, 95% CI: 1.4-3.8). In females also, exposure to chlorinated solvents indicated a urothelial cancer risk. Because of small numbers the risk evaluation for females should be treated with caution. CONCLUSIONS: Occupational exposure to aromatic amines could not be shown to be as strong a risk factor for urothelial carcinomas as in the past. A possible explanation for this finding is the reduction in exposure over the last 50 years. Our results strengthen the evidence that PAH may have a carcinogenic potential for the urothelium. Furthermore, our results indicate a urothelial cancer risk for the use of chlorinated solvents.

Aged↗

Occupational risk factors for renal cell carcinoma: agent-specific results from a case-control study in Germany. MURC Study Group. Multicenter urothelial and renal cancer study.

BACKGROUND: This case-control study was conducted to estimate the renal cell cancer (RCC) risk for exposure to occupation-related agents, besides other suspected risk factors. METHODS: In a population-based multicentre study, 935 incident RCC cases and 4298 controls matched for region, sex, and age were interviewed between 1991 and 1995 for their occupational history and lifestyle habits. Agent-specific exposure was expert-rated with two job-exposure matrices and a job task-exposure matrix. Conditional logistic regression was used to calculate smoking adjusted odds ratios (OR). RESULTS: Very long exposures in the chemical, rubber, and printing industries were associated with risk for RCC. Males considered as 'substantially exposed to organic solvents' showed a significant excess risk (OR = 1.6, 95% CI : 1.1-2.3). In females substantial exposure to solvents was also a significant risk factor (OR = 2.1, 95% CI : 1.0-4.4). Excess risks were shown for high exposure to cadmium (OR = 1.4, 95% CI : 1.1-1.8, in men, OR = 2.5, 95% CI : 1.2-5.3 in women), for substantial exposure to lead (OR = 1.5, 95% CI : 1.0-2.3, in men, OR = 2.6, 95% CI : 1.2-5.5, in women) and to solder fumes (OR = 1.5, 95% CI : 1.0-2.4, in men). In females, an excess risk for the task 'soldering, welding, milling' was found (OR = 3.0, 95% CI : 1.1-7.8). Exposure to paints, mineral oils, cutting fluids, benzene, polycyclic aromatic hydrocarbons, and asbestos showed an association with RCC development. CONCLUSIONS: Our results indicate that substantial exposure to metals and solvents may be nephrocarcinogenic. There is evidence for a gender-specific susceptibility of the kidneys.

Carcinoma, Renal Cell↗

[Radiologic examination of the spine in "back problems" of the standing horse].

The radiological examination of the thoracolumbar spine of a horse with a potential back problem is most important in order to come to a diagnosis and the imaging method of choice. The use of parallel grid-cassettes, appropriate films, rare earth screens and aluminium filters requires radiographic equipment with an output of 60-120 kV and 25-90 mAs. By use of this technique in the standing horse it is possible to obtain radiographs of the summits of the dorsal spinal processes of the thoracolumbar spine from the first thoracic (T1) to approximately the third of fourth lumbar vertebrae (L3/4). Since the thickness of soft tissue is increasing from distal to proximal it is necessary to increase the output to image the processus articulares craniales et caudales. Therefore additional radiographs have to be taken.

Animals↗

[Radiologic description of the growth plates of the atlas and axis in foals].

Fractures of the first two cervical vertebrae, atlas and axis, may occur in foals for different reasons, e.g. in cases of a fall, going head over heels or when being hit by a hoof. The tentative clinical diagnosis can be confirmed by x-raying the standing animal, with aid of computed tomography in the anaesthetized foal respectively. The growth plates however, and their time of closure have to be considered when interpreting radiographs. In the atlas there are two ventrolateral plates and one dorsomedian cartilagineous plate. Only the dorsal plate, however, can be found in the dorsoventral projection up to an age of about 12 months. The ventrolateral growth plates which have closed at about six months of age cannot be seen in either ther dorsoventral or laterolateral projection. In transversely oriented CT-scans all of the three centres of ossification can easily be made visible in the atlas. In the axis the cartilagineous gaps between the dens axis and the cranial epiphysis as well as the cranial and caudal epiphyseal growth plate can be shown in normal x-radiographs in both planes of projection. Besides this there are growth plates between the corpus vertebrae and the arcus vertebrae in the axis which cannot be seen in either radiographic projection. They become clearly visible in transversal CT-scans and are ossified at the age of three to four months. At the end of the first year the growth plates between the dens axis and the cranial epiphysis have closed. The cranial and caudal epiphyseal plate are gone at an age of about four to five years.

Animals↗

The analysis of case-control studies under validation subsampling.

In case-control studies, one often finds that covariates are missing or measured with error in the entire sample, whereas complete or exact covariate information is available only in a subsample. This paper discusses the analysis of case-control studies under a double-sampling scheme, where at the first stage covariates are measured with error or missing, and at the second stage are validated in a subsample. The method proposed combines the risk information from both samples by assuming that (1) the disease incidence model is logistic, (2) the partial or proxy information takes on finitely many values, and (3) the error is non-differential. The estimator is obtained by jointly fitting logistic models to the first and second stage data, a variance formula is presented. Parameters can be estimated by use of standard packages for dose-response data. Data from an ongoing case-control study on lung cancer serve as an example.

Aged↗

Attributable risk estimation from case-control data via logistic regression.

By fitting an unconditional logistic regression model to unmatched case-control data, an estimate of the joint population attributable risk for the factor included is obtained. This estimate and its asymptotic variance can easily be computed from the intercept parameter and its asymptotic variance. A generalization to the analysis of stratified data with large strata enables the calculation of stratum-specific attributable risks and their variances via stratum-specific intercept parameters. If sampling of cases is independent of strata, an estimate of the summary attributable risk and its asymptotic variance may be obtained as a weighted sum of the stratum-specific attributable risks.

Biometry↗

Circadian rhythms of cell cycle processes in the marine dinoflagellate Gonyaulax polyedra.

The circadian expression of several growth properties was examined in the dinoflagellate Gonyaulax polyedra under constant light and light-dark conditions. The cell concentration, mean cell volume and rate of DNA synthesis varied in a circadian rhythm, with the primary maximum of cytokinesis and DNA synthesis at about dawn. High rates of cell mortality also occurred during phases related to events of cytokinesis, and may be important in the expression of the other rhythms and in "red tide" generation. Flow-cytofluorimetric analysis indicated that cells of a population contain either a relatively high or a low amount of DNA, but the proportion of cells in each of these classes and the absolute amount of DNA in each cell varied rhythmically depending on the circadian time. This DNA-distribution pattern was unlike the usual G1-S-G2+M pattern typical of eukaryotic cell populations. Isotopically labelled thymidine, used as a marker of DNA synthesis, was continuously incorporated; but the incorporation rate fluctuated in a regular pattern that repeated each circadian period.

Animals↗

Neutrophil leucocyte chemotaxis is not induced by a spatial gradient of chemoattractant.

Chemotaxis and directed locomotion of neutrophil leucocytes are generally thought to be determined by the directed response of the cell to stable, spatial gradients of chemoattractants. In most cases, however, cells are also exposed to characteristic temporal changes in the attractant concentration during the lifetime of the gradient, especially as it develops. We have attempted to test whether neutrophils can respond to a spatial gradient in which these temporal changes are essentially absent. Gradients of formyl-peptides were made across a narrow barrier of agarose gel that separated two fluid reservoirs, and the cells were observed cinematographically as they moved between gel and glass. In gradients predeveloped at low temperature, at which cell motion and responses to attractant were inhibited, neutrophils showed no tendency to accumulate up-gradient when warmed to 37 degrees C. Yet their speed and turning behaviour was related to the local concentration of formyl-peptide. However, gradients that developed at 37 degrees C, whilst the cells were responsive, elicited directed locomotion. We also tested populations that were either spreading into or already evenly distributed across micropore filters to see how cells might sense directional cues. We reasoned that evenly distributed populations could accumulate in a spatial gradient only if cells were able to 'read' it. However, no redistribution occurred without an applied impulse of attractant. It seems that the oriented, temporal component of an attractant signal is essential if a directed response (i.e. non-random turning) is to occur; a spatial gradient of soluble attractant alone does not induce neutrophil accumulation or taxis. This finding has implications for the termination of the acute inflammatory response, for clinical tests of leucocyte behaviour and for morphogen signal interpretation by cells in developing tissues.

Animals↗

Evidence on the local character of spatial frequency channels in the human visual system.

The question has been raised as to whether there exists any transfer of information between neighboring retinal areas following presentation of spatially limited optical stimuli. Our experiments were aimed at mechanisms by which spatial frequency information could be transferred from one part of the visual field to another. Within a 0.9 degree X 2.5 degree section of the 3.6 degree X 2.5 degree testfield the observers adapt to a number of moving sinusoidally-modulated brightness or hue gratings of different spatial frequencies. As known by many publications the sensitivity to spatial frequencies changes in the adapted area. We find that this influence on the contrast threshold decreases as the distance to the adaptation section increases. Hence our results suggest mechanisms within the visual system mathematically best described by a local spectrum analysis.

Adaptation, Ocular↗

Subacute toxicity of 1,1,1-trichloroethane, noise, and their combination in rats.

The metabolism of the xenobiotics 1,1,1-trichloroethane (TCE) or 1,1,2-trichloro-1,2,2-trifluoroethane and endogeneous substrates may be changed under physiological stress situations. We studied long-term effects on rats exposed to TCE, noise pollution, and their combination. The experiments were performed in a special set-up where four parallel groups of rats were simultaneously exposed to defined conditions the chemical vapor; the noise pollution of 90 dB; their combination; and a control group without any exposure. The vapor of TCE was applied at a concentration of 200 ppm/8 hr or of 2000 ppm/12 hr for 84 days each. The experiments were performed with TCE from two different commercial sources. One of those TCE preparations caused effects at the high dosage level in terms of enhanced levels of the relation of liver to body weight; liver microsomal protein content; liver microsomal monooxygenase activity; and 3,4-dihydroxyphenylglycol excretion in urine. Eight other physiological and biochemical parameters were not changed.

Animals↗

Chemoattraction and chemotaxis in Dictyostelium discoideum: myxamoeba cannot read spatial gradients of cyclic adenosine monophosphate.

Myxamoebae of the morphogenetic cellular slime mold Dictyostelium discoideum are thought to be able to accurately read and respond to directional information in spatial gradients of cyclic AMP. We examined the spatial and temporal mechanisms proposed for chemotaxis by comparing the behavior of spreading or evenly distributed cell populations after exposure to well-defined spatial gradients. The effects of gradient generation on cells were avoided by using predeveloped gradients. Qualitatively different responses were obtained using (a) isotropic, (b) static spatial, or (c) temporal (impulse) gradients in a simple chamber of penetrable micropore filters. We simulated models of chemotaxis and chemokinesis to aid our interpretations. The attractive and locomotory responses of populations were maximally stimulated by 0.05 microM cyclic AMP, provided that cellular phosphodiesterase was inhibited. But a single impulse of cyclic AMP during gradient development caused a greater and qualitatively different attraction. Attraction in spatial gradients was only transient, in that populations eventually developed a random distribution when confined to a narrow territory. Populations never accumulated nor lost their random distribution even in extremely steep spatial gradients. Attraction in spatial gradients was inducible only in spreading populations, not randomly distributed ones. Thus, spatial gradients effect biased-random locomotion: i.e., chemokinesis without adaptation. Cells cannot read gradients; the reaction of the cells is stochastic. Spatial gradients do not cause chemotaxis, which probably requires a sharp stimulant concentration increase (a temporal gradient) as a pulse or impulse. The results also bear on concepts of how embryonic cells might be able to decipher the positional information in a morphogen spatial gradient during development.

3',5'-Cyclic-AMP Phosphodiesterases↗

An application of gas chromatography mass spectrometry to the quantitation of substances and their labelled variants.

A method is proposed for the quantitative estimation of a substance and its labelled analogue using the selected ion monitoring technique of gas chromatography mass spectrometry, in which estimation is achieved without a third labelled analogue as internal standard. In a first measurement the ratio of natural to labelled substance is established. Then a known amount of either labelled or natural compound is added, the isotope ratio is determined a second time and from these two measurements the mass amounts can be calculated. When applied to the heptafluorobutyrates of androstenedione and progesterone about 10 pg of 14C labeled compounds can be determined in the presence of 1 ng of the natural substances.

Androstenedione↗

Simultaneous quantitative estimates of several isotopically labelled substances in the picogram range with selected ion monitoring.

The use of a model developed by the authors for the simultaneous quantitative determination of several isotopically labelled substances of the same chemical structure is described in detail for a two substance system. A computational flow chart is included. An example using natural estradiol and 4-[14C] labelled estradiol with manifold deuterated estradiol as an internal standard is presented. The basis of the model is discussed.

Chromatography, Gas↗