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Biomedical subjects

U Feldmann

Publications and source records attributed to U Feldmann.

At least 19 recordsLinked to original sources

Assessing the state of population health by age-adjusted life expectancies.

OBJECTIVES: A gain in life expectancy of a population is commonly interpreted as an effect of improved health care. After the reunion of Germany in 1990 life expectancy at birth grew extremely in the new federal states. Within one decade after reunion the new federal states had a gain in life expectancy of about five years while the gain in the old federal states was only about two years. METHODS: It has been widely argued that this phenomenon is caused by an obviously improved public health service and environmental protection or even by an increased social status in the new federal states. On the other hand, the median population age grew rapidly in the new federal states, caused by a dramatic reduction of the birth rate as well as a high emigration rate of young people. Using real time series for three selected federal states and for the total Federal Republic of Germany, it is derived that most of the gain in life expectancy is explained by population ageing. RESULTS: An elementary probabilistic procedure is proposed allowing for estimating the amount in life expectancy not attributable to population ageing. CONCLUSIONS: The age-adjusted life expectancy can be regarded as an unbiased measure of a populations' state of health that stays comparable both over time and across countries.

Germany↗

Expression of early placenta insulin-like growth factor in breast cancer cells provides an autocrine loop that predominantly enhances invasiveness and motility.

Early placenta insulin-like growth factor (EPIL) is expressed by a subpopulation of the Her2-positive SKBR3 breast cancer cell line displaying high motility and transendothelial invasiveness in vitro, as recently shown by our group. As a consequence of this, we established cellular models by generating an EPIL-overexpressing SKBR3 cell line, knocked down EPIL by adding specific small interfering RNA (siRNA) to those cells and produced EPIL-enriched and depleted serum-free culture media. EPIL-expressing cells as well as EPIL-induced SKBR3 cells acquired a high capacity for transendothelial invasiveness. We observed a thin and outspread morphology caused by enhanced formation of lamellipodia, i.e. protrusions in the initial phase of motility. In parallel, Her2-positive MDAHer2 breast cancer cells also showed increased invasiveness when induced by EPIL-conditioned medium. A downstream signaling impact of EPIL could be observed in the form of reduced phosphorylation of Her2, erk1/2 and akt, while phospholipase Cgamma1 phophorylation remained unaffected. As an in vivo model for highly motile tumor cells, Paget's disease of the nipple showed simultaneous EPIL and Her2 expression upon immunohistochemical examination using specific antibodies. Such experimental data have been translated to a clinical setting by using a prognostic tissue microarray established from 603 breast cancer cases. Survival data analysis found a significant association between expression levels of EPIL and 5-year overall survival that was dose dependent: EPIL (negative) 84%, EPIL (moderately positive) 77%, EPIL (strongly positive) 48% (P < 0.005). One particular subgroup (7.6% of the cases with full clinical records) that comprised tumors simultaneously expressing EPIL and Her2 represented patients with the poorest 5-year overall survival. The results suggested that EPIL might be a cancer cell-produced growth factor that influences lateral Her2 signaling. Moreover, EPIL may be induced by factors apart from Her2 and may independently provide signaling for cancer invasion and motility.

Autocrine Communication↗

[A population-based survey of critical care].

OBJECTIVES: Results of a population-based survey of critical care in a German state are presented. The indication for critical care was derived using the APACHE-II score,which measures the physiologic state of patients, and the TISS-28 score as a measure for expenditure of critical care. METHODS: During 3 months all adult patients of intensive care units in Saarland, a German state with 1.08 million residents,were included. All kinds of hospitals were involved. Completeness and validity of data are proved. RESULTS: The TISS score was registered daily on 13,391 adult patients with 54,503 days, the APACHE score during admission and discharge of intensive care units only. The correlation between the scoring-systems and indication, kind of care (critical care vs. intermediate care), kind of hospital, and ICD-10 diagnoses is analysed in this paper. CONCLUSIONS: In this study the population-based critical care in a state is analysed the first time. It completes previously published studies,which were performed at the level of hospitals and departments.

APACHE↗

Ordinal classification in medical prognosis.

OBJECTIVES: Medical prognosis is commonly expressed in terms of ordered outcome categories. This paper provides simple statistical procedures to judge whether the predictor variables reflect this natural ordering. METHODS: The concept of stochastic ordering in logistic regression and discrimination models is applied to naturally ordered outcome scales in medical prognosis. RESULTS: The ordering stage is assessed by a data-generated choice between ordered, partially ordered, and unordered models. The ordinal structure of the outcome is particularly taken into consideration in the construction of allocation rules and in the assessment of their performance. The specialized models are compared to the unordered model with respect to the classification efficiency in a clinical prognostic study. CONCLUSIONS: It is concluded that our approach offers more flexibility than the widely used cumulative-odds model and more stability than the multinomial logistic model. The procedure described in this paper is strongly recommended for practical applications to support medical decision-making.

Anesthesia↗

EEG gamma-band phase synchronization between posterior and frontal cortex during mental rotation in humans.

The main purpose of the present paper was: (1) to study the phase synchronization pattern in the gamma-band while performing the classical Shepard-Metzler task of mental rotation; (2) to investigate the role of musical training; and (3) to study hemispheric differences in the degree of synchronization during mental rotation. Multivariate electroencephalograph signals from 20 male subjects (ten musicians and ten non-musicians) were recorded while performing the mental rotation task and also at resting condition. Phase synchronization was measured by a recent index, mean phase coherence. It was found that synchronization between frontal cortex and right parietal cortex was significantly increased during mental rotation with respect to rest, whereby musicians showed significantly higher degrees of synchronization than non-musicians. Left hemispheric dominance in the degree of phase synchronization, stronger in the posterior right parietal and occipital regions, was observed in musicians. Right hemispheric dominance was generally observed in non-musicians.

Brain Mapping↗

Methods of ordinal classification applied to medical scoring systems.

Scoring systems are used in nearly all fields of medicine for evaluation of the state of a disease. The prediction performance of scoring systems with respect to an ordinal outcome scale is investigated, based on grouped continuous logistic models as well as on an extension of the stereotype logistic regression model. The latter is a canonical approach, which allows assessment of properties of outcome categories such as partial and total ordering, distinguishability and allocatability. The approach is applied to a data set of patients with injuries of the head.

Cerebral Arteries↗

Multivariate logistic analysis of dose-effect relationship and latency of radiomyelopathy after hyperfractionated and conventionally fractionated radiotherapy in animal experiments.

PURPOSE: We examined in rats whether the radiation tolerance of spinal cord is enhanced by using hyperfractionated radiotherapy compared to a conventional schedule. Higher tolerable doses to the spinal cord would allow dose escalation to the tumor and thus possibly lead to higher cure rates, especially in tumors with high cell proliferation. METHODS AND MATERIALS: Cervical spinal cord of 276 healthy rats was irradiated over 6 weeks hyperfractionally with single doses ranging from 0.75-2.5 Gy up to total doses ranging from 45-150 Gy (60 fractions) and conventionally with single doses of 1.5-4.0 Gy up to total doses of 45-120 Gy (30 fractions). The rats were examined neurologically and sacrificed when paralysis of the hind legs occurred. After fixation, spinal cord was removed and examined histologically. Dose-effect relationship and latency from the beginning of radiotherapy to the onset of paralysis were computed and analyzed using a multivariate logistic regression model. RESULTS: The model fitted the observed data excellently. There were highly significant effects both for the dose level and for the treatment regimen. Latency analysis showed earlier and more intense acute side effects after hyperfractionation but radiomyelopathy occurred markedly later. CONCLUSIONS: The sparing effect of hyperfractionation on spinal cord as predicted by radiobiologists could be confirmed in our experiments. Thus, it seems possible to escalate tumor doses using hyperfractionation without enhanced risk to spinal cord but with higher probability of tumor cure.

Animals↗

Medical information processing: an interactive course for the Internet.

Medical students in Germany have to study the basics of medical information processing within a special curriculum which is part of the ecological course. This curriculum offers an introduction to principles of medical informatics. Starting with a conventional textbook, a computer-based training (CBT) program has been developed using the technologies of the internet and the World Wide Web (WWW). Features of the program include a well structured presentation of the information within the software and a high degree of interactivity. Early experiences suggest that this program enhances the learning in the domain of medical information processing. The program may be viewed via the URL: htfp.//www.med-rz.uni-sb.de/med_fak/imbei/pro jekt.

Education, Medical↗

[Validation of the prognostic accuracy of neurosurgical admission scales after rupture of cerebral aneurysms].

The course of 185 patients operated for a ruptured intracranial aneurysm at the University of Saarland between 1991 and 1993 has been followed up. The main emphasis of the investigation was placed on the scrutiny of the coma scales on admission (Hunt & Hess-Scale, Glasgow Coma Scale and WFNS-Scale [= World Federation of Neurological Surgeons]) with regard to the outcome. Outcome was defined as the patients' state six months after aneurysm rupture according to the Glasgow Outcome Scale. The sensitivities, specifities and predictive values of almost all scale grades were poor. The Hunt&Hess-Scale was the one with the best correlation. By half the patients with the worst scale grades on admission had a good outcome. A gradation of the outcome with regard to the middle admission grades has not been identified. These observations have been demonstrated by using ROC (Receiver Operating Characteristic)-curves. The admission scales are not suitable to give a definite prognosis and do not justify any decision neither pro nor contra an operation. A lot of parameters besides the neurological findings have an effect on the prognosis. Additionally, unexpected complications may occur in the pre- and postoperative phase. The score values determined at the day of operation have shown a more precise prognosis than the values determined immediately after hospitalization. Therefore the evaluation of the most relevant phase could improve the prognostic value of the scales.

Adult↗

Chronic spondylogenic cervical myelopathy. A critical evaluation of surgical treatment after early and long-term follow-up.

In the past, chronic spondylogenic cervical myelopathy has been thought of being a disease often resistant to neurosurgical therapy. 56 out of 70 patient treated by laminectomy or different ventral fusion procedures improved immediately following operation. Only 36, however, continued to be improved at follow-up 5 to 8 years later, whereas additional 8 had worsened again, and another 5 mean-while had died due to myelopathy. Laminectomy turned out to be the least successful procedure of treatment. Nevertheless, early diagnosis, early operation, appropriate and individual surgical procedures, careful re-evaluation at follow-up, and -- if needed -- an early decision for a second-step operation can impressively improve the prognosis.

Adult↗

Design and analysis of drug safety studies, with special reference to sporadic drug use and acute adverse reactions.

A methodological approach for analysis of drug safety data which permits the calculation of risk measures for intermittent exposures and acute adverse reactions is presented. This method allows for the observation of exposures that are temporary and which may be of varying lengths, as in the application of analgesics. Risk measures are determined using the relative risk and the excess risk to assess drug safety. The latter has important public health policy significance for decision making about the safety of a drug. The model depends on a simple counting process and allows for the consideration of concomitant variables which can likewise exert an influence on the absolute risk. Hazard estimates are derived by the maximum likelihood method. Three possible approaches to the planning and analysis of studies of drug safety are discussed: cohort studies, case-cohort studies, and case studies. The case study represents an approach which requires only data from the individuals in which an adverse reaction has occurred. The different sampling designs are illustrated using data from a study investigating the etiology of wound healing disorders.

Acute Disease↗

Epidemiologic assessment of risks of adverse reactions associated with intermittent exposure.

Measures of risk of adverse reactions, such as the absolute risk, the relative risk, and the excess risk, are analyzed for individuals who are exposed occasionally for periods of varying duration. This type of exposure is of particular importance for the epidemiologic assessment of drug safety. A Poisson point process model that allows for the simultaneous consideration of concomitant factors is derived for the estimation of the hazard rates. The model can judge acute adverse reactions and is applicable not only for rare risks since an undesired effect may occur repeatedly for an individual. Hazard estimation is achieved with the aid of the maximum likelihood method for several sampling designs, such as cohort studies, case-cohort studies, and case studies. In the latter design only those individuals who have had an adverse reaction during the time of observation are considered for hazard estimation. An application to the analysis of wound-healing impairments is given.

Case-Control Studies↗

Robust bivariate errors-in-variables regression and outlier detection.

A bivariate regression model is introduced where both variables are subject to error. The structural regression line is equivariant against interchanging coordinates and permits bivariate calibration, i.e. the prediction of one variable by means of the other. Maximum likelihood and robust parameter are estimated, based on order statistics. Residual analysis and outlier detection are performed. The model is applied to the comparison of clinical chemical analytical methods.

Hematocrit↗

Pharmacokinetics of 5-fluorouracil after short systemic infusion: plasma level at the end of the distribution phase as an indicator of the total area under the plasma concentration-time curve.

The correlation between single plasma concentration (CP) values of 5-fluorouracil (FU) after a 10-minute i.v. infusion and the total area under the plasma concentration-time curve (AUC) has been studied in 26 cancer patients. FU dose was either 320-550 mg/m2 (seven patients, 13 treatments) or 610-960 mg/m2 (19 patients, 30 treatments). Linear single CP-AUC relationships were found in both dose groups with the CPs at 1, 5, 10, 15, and 30 minutes after the end of infusion. Parameters of linear regression of AUC on single CP differed between the two dose groups. For the high-dose group, the single CPs at repeated treatments were tested as estimators of the total AUC at these treatments, using calibration lines relating total AUC to single CP, which were derived from the data of the first (or only) treatments of all patients. The "best" AUC estimators of the total AUC were the CPs at 10 and 15 minutes after the end of infusion, with a bias of only 2% and an imprecision of only 11% of the AUC values directly determined from the complete concentration-time profiles of the repeated treatments. Because of the close correlation between these single CPs and the total AUC, these CPs should be considered equivalent to the AUC as an overall index of individual FU kinetics after brief infusion of high doses.

Adult↗