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Annette Pfahlberg

Publications and source records attributed to Annette Pfahlberg.

17 recordsLinked to original sources

Comparison of confidence intervals for adjusted attributable risk estimates under multinomial sampling.

The epidemiologic concept of the adjusted attributable risk is a useful approach to quantitatively describe the importance of risk factors on the population level. It measures the proportional reduction in disease probability when a risk factor is eliminated from the population, accounting for effects of confounding and effect-modification by nuisance variables. The computation of asymptotic variance estimates for estimates of the adjusted attributable risk is often done by applying the delta method. Investigations on the delta method have shown, however, that the delta method generally tends to underestimate the standard error, leading to biased confidence intervals. We compare confidence intervals for the adjusted attributable risk derived by applying computer intensive methods like the bootstrap or jackknife to confidence intervals based on asymptotic variance estimates using an extensive Monte Carlo simulation and within a real data example from a cohort study in cardiovascular disease epidemiology. Our results show that confidence intervals based on bootstrap and jackknife methods outperform intervals based on asymptotic theory. Best variants of computer intensive confidence intervals are indicated for different situations.

Adult↗

Biological monitoring of welders exposed to aluminium.

To evaluate an adequate strategy for biological monitoring of aluminium (Al), a group of 62 Al welders (age in 1999: 23-51 years, median 35 years) was surveyed annually from 1999 to 2003 by determination of pre- and post-shift Al in urine and plasma. Biomonitoring was supplemented by personal air measurements of the total dust concentration. The welders' internal exposure was compared to the exposure of 60 non-exposed assembly workers (age in 1999: 21-51 years, median: 36 years) who were surveyed in 1999, 2001 and 2003. Having a nearly constant dust exposure, median concentrations of Al in urine (Al in plasma) of the welders decreased from 40.1 microg/g to 19.8 microg/g creatinine (8.7 to 4.6 microg/l). For the control group the median levels of Al in urine (plasma) ranged from 4.8 microg/g to 5.2 microg/g creatinine (2.4-4.3 microg/l) indicating a higher sensitivity for the marker Al in urine. No systematic differences have been found between pre- and post-shift internal exposure. This might be caused by the slow elimination kinetics and low systemic bioavailability of Al. A correlation analysis did not yield close relationships between dust exposure, Al in plasma and Al in urine underlining the importance of biomonitoring for assessment of Al exposure.

Adult↗

Fat necrosis after conserving surgery and interstitial brachytherapy and/or external-beam irradiation in women with breast cancer.

PURPOSE: To investigate the incidence of fat necrosis, breast tissue fibrosis and breast pain after conserving surgery and accelerated partial-breast irradiation (APBI, group A), whole-breast external-beam irradiation (EBRT, group B), or EBRT combined with an interstitial boost (EBIB, group C) in women with breast cancer. PATIENTS AND METHODS: 85 patients who received breast-conserving therapy from 02/2000 to 03/2002 were analyzed. 30 patients received EBRT, 33 patients APBI, and 22 patients EBIB. Median follow-up was 35.5, 35.0, and 37.5 months, respectively. Fat necrosis was detected and rated by mammograms, fibrosis and pain were clinically rated with the LENT-SOMA scores. RESULTS: The incidence of fat necrosis was 15.3% for all patients; and 15.2%, 20.0%, and 9.0% for groups A, B, and C, respectively. The 3-year fat necrosis-free survival probability was 83%, 76%, and 95% (difference not significant). The mean time to first diagnosis of fat necrosis was 25.6, 26.2, and 26.0 months. No patient needed surgical intervention because of fat necrosis-related pain. Fibrosis was present in 27.3%, 63.3%, and 77.3% (p < 0.001), breast pain in 9.0%, 33.4%, and 18.1% (p < 0.05). CONCLUSION: Asymptomatic fat necrosis is a common finding after both percutaneous and interstitial irradiation after breast-conserving surgery. This analysis did not support the hypothesis that APBI with multicatheter implants leads to higher rates of fat necrosis, fibrosis, or pain.

Adipose Tissue↗

The prevalence of contact allergy differed between population-based and clinic-based data.

OBJECTIVE: Epidemiologic evidence on contact allergy (CA) largely relies on clinical studies. However, the effects of the selection process until consultation as patient are largely unclear. STUDY DESIGN AND SETTING: Prevalences of contact allergy to important allergens estimated from the population-based nested case-control study "KORA Allergy Study" in Augsburg, Germany (a subsample from the third MONICA survey in 1997/1998, n=1141), were compared with proportions found in the Department of Dermatology of the Augsburg Municipal Hospital in patients of similar age patch tested between 1997 and 2000 (n=555). Prevalences were standardized for sex, age, and atopic dermatitis as potential confounders. RESULTS: Among the 25 substances tested, the fragrance mix (MONICA, estimated from the KORA Allergy Study: 11.4%, hospital: 12.9%) and nickel (MONICA: 9.9%, hospital: 12.9%) were the most common allergens. Larger differences between prevalences were noted particularly with ingredients of topicals used to treat varicose ulcers-a speciality of the Augsburg department, which is also reflected by comparing the department with the whole Information Network of (n =40) Departments of Dermatology (IVDK). CONCLUSION: This locally matched comparison illustrates the differential effect of selection until presentation in dermatological departments.

Adult↗

Induction of the photoaging-associated mitochondrial common deletion in vivo in normal human skin.

Mutations of mitochondrial (mt) DNA such as the 4977 base-pair large-scale deletion, also called common deletion, are increased in photoaged skin. Direct evidence for their induction by chronic exposure to ultraviolet (UV) radiation in vivo in human skin has remained elusive however. Furthermore, their fate after induction is unclear. Previously unirradiated skin of 52 normal human individuals was repetitively exposed to physiological doses of UVA light. Skin and blood specimens were investigated for the presence of mtDNA mutations employing semiquantitative nested PCR, as well as real-time PCR, after 2 weeks of UV exposure and the content of the common deletion was followed up for up to 16 mo after cessation of irradiation. As assessed by both methods, repetitive UV exposure led to an approximately 40% increase in the levels of the common deletion in normal human skin. The majority of deletions were detectable in the dermis also showing the biggest increase, whereas in the epidermis only residual levels and no increase were found. Nine individuals were examined up to 16 mo after cessation of UV exposure and some showed accumulation up to 32-fold. Thus, mtDNA mutations are induced in the human skin by repetitive UV exposure. In addition, these mutations seem to represent long-term in-vivo biomarkers for actinic damage in the human skin.

Adolescent↗

Lung function among workers in the soft tissue paper-producing industry.

OBJECTIVES: To describe lung function in correlation with information on exposure to dust and fibers in soft tissue paper-producing factories in Germany. METHODS: Ambient monitoring was performed for inhalable, respirable dust and fibers in nine soft tissue paper-producing factories. In a study group of 1,047 workers (189 control subjects, 240 workers with moderate exposure, and 618 workers with high exposure), spirometry (FVC, FEV(1)) was performed. Information on occupational history, duration of exposure, workshop within the company, former occupational exposures, and smoking habits were collected. By employing multiple linear regression modeling, the potentially confounding effects of age, sex, body mass index, smoking habits, and factory were incorporated into the analysis of FVC, FEV(1), and FEV(1) in percent of FVC (FEV(1)%FVC). By employing a logistic regression model, odds ratios were calculated for FVC < 80% predicted in different exposure subgroups. RESULTS: The mean concentrations for inhalable, respirable, and fibrous dusts were 12.4 mg/m(3), 0.28 mg/m(3), and 420,000 fibers per cubic meter. With relation to cumulative dust and fiber exposure, a decrease of FVC from 105.4% predicted to 96.9% predicted (dust) and 97.1% predicted (fibers) in the subgroup with highest cumulative exposure was observed. For FEV(1), a decrease from 107.3% predicted to 103.0% predicted (dust) and 102.8% predicted (fibers) was found. The parameter estimates show dose-response relationships that are more pronounced for FVC compared to FEV(1). FEV(1)%FVC did not change significantly with increasing cumulative exposure, indicating a restrictive pattern of the findings. CONCLUSIONS: Due to high ambient dust concentrations and the observed adverse effects on lung function, a reduction of dust exposure and secondary preventive measures is advised.

Adult↗

Na(+)-channel modulation, a new principle of inotropic intervention: effects on hemodynamic and myocardial energetics in the immature rabbit heart.

Na+-channel modulators exert their positive inotropic action without affecting the adenylate-cyclase pathway by an increase in the open probability of the sarcolemmal Na+ channels. Although inotropic effects in neonatal hearts are less pronounced compared with adult hearts, the Na+-channel modulator BDF 9148 increases contractility and relaxation velocity in immature myocardium. Effects on hemodynamics and myocardial energetics are not known. Therefore, we studied the Na+-channel modulator BDF 9148 in isolated antegrade perfused rabbit hearts of different ages (2-28 d) and compared the effects with isoproterenol, enoximone, and ouabain. ANOVA showed significant effects in the concentration response curves for heart rate, stroke volume, cardiac output, and oxygen consumption but not for myocardial efficiency (p = 0.06). Age-dependent differences were observed for heart rate and stroke volume. Administration of BDF 9148 resulted in a maximal increase in stroke volume and cardiac output up to 25% in neonatal and 40% to 60% in adult preparations. Heart rate decreased by 15% in adult hearts only. Myocardial oxygen consumption was increased in a concentration-dependent manner between 25% in neonatal and 50% in adult hearts. Myocardial efficiency was increased by 35% in adult and by 10% in neonatal preparations. Although positive hemodynamic and energetic effects were less pronounced in immature compared with adult hearts, neonatal hearts also profited from the administration of the Na+-channel modulator BDF 9148. Further studies are necessary to clarify the risk of arrhythmia during application of Na+-channel modulators such as BDF 9148.

Age Factors↗

The association between ambient air conditions (temperature and absolute humidity), irritant sodium lauryl sulfate patch test reactions and patch test reactivity to standard allergens.

To support the decision as to whether erythematous patch test reactions to allergens are irritant or allergic, sodium lauryl sulfate (SLS, 0.5% in water) has been added to the standard patch tests since July 1996 in the Dortmund Department of Dermatology. Data on 1600 patients patch tested up until June 2001, as well as standardized data on ambient temperature and humidity obtained by the German Meteorological Service, were included in a logistic regression analysis taking age, sex and atopy as potential confounders into account. The pattern of association was heterogeneous: while doubtful reactions to nickel sulfate were significantly associated with dry/cold weather conditions, but not with SLS reactivity, the opposite was observed for lanolin alcohol, benzocaine and Myroxylon pereirae resin (balsam of Peru). Doubtful reactions to other allergens, namely formaldehyde, fragrance mix or p-phenylenediamine, were associated with both factors. For several other allergens of the standard series, no distinct, significant pattern could be discerned. In conclusion, meteorological conditions and SLS reactivity independently contribute information on individual irritability at the time of patch testing, and both should be considered.

Allergens↗

Effects of different inotropic interventions on myocardial function in the developing rabbit heart.

The development of the mammalian heart is characterized by substantial changes in myocardial performance. We studied the ontogeny of myocardial function with and without various inotropic interventions in the developing isolated, antegrade-perfused rabbit heart (2d, 8d, 14d, 28d, n = 96). Myocardial function was related to the protein expression of the sarcolemmal Na(+)-Ca2+ exchanger and to the sarcoplasmic Ca(2+)-ATPase. In neonatal hearts an age-dependent increase in maximal developed pressure velocity (dP/dtmax) by 45% and peak negative pressure velocity (dP/ dtmin) by 75% within days 2 to 8 were observed. In response to inotropic intervention with isoproterenol, ouabain, calcium and the Na(+)-channel modulator BDF 9148, dP/dtmax and dP/dtmin increased in a concentration dependent manner. Significant differences between neonatal, juvenile and adult hearts could be demonstrated in a repeated measurement ANOVA model on the concentration-response curves for BDF 9148 (dP/dtmax and dP/dtmin), ouabain (dP/dtmin) and calcium (dP/dtmin), but not for isoproterenol. At the maximum isoproterenol concentration of 1 micromol/l, the increase in dP/dtmax and dP/dtmin was significantly higher in adult compared to neonatal hearts (t-test, p < 0.01). The significant decline of the Na(+)-Ca2+ exchanger protein expression from neonatal (1822 +/- 171) to adult hearts (411 +/- 96 S.E.M. [units per 20 microg protein], p < 0.01) was related to an increase in myocardial function (dP/dtmax r = 0.63, p < 0.01, dP/dtmin r = 0.62, p < 0.01). Contractility, relaxation and the observed positive inotropic effects were in general significantly lower in neonatal compared to adult hearts. In the individual heart an increase in contractility and relaxation was related to a decrease in Na(+)-Ca2+ exchanger expression.

Adrenergic beta-Agonists↗

T1 breast cancer: identification of patients at low risk of axillary lymph node metastases.

OBJECTIVE: The status of the axillary lymph nodes is one of the most important prognostic factors in patients with breast cancer. A panel of molecular markers of tumor aggressiveness in addition to conventional clinical and histopathologic features were analyzed in an attempt to identify a subgroup of patients with a low risk of axillary lymph node metastases. MATERIAL AND METHODS: Data from 358 patients with T1 breast cancer who underwent level I/II axillary lymph node dissection (ALND) were investigated. Hormone receptor status, Ki-67, S-phase fraction, DNA ploidy, HER-2/neu, p53, epidermal growth factor receptor, urokinase type plasminogen activator, plasminogen activator inhibitor-1, bone marrow micrometastases as well as patient age, menopausal status, tumor site, tumor size, histologic type, tumor grade, carcinoma in situ, multifocality, and lymph vascular invasion (LVI) were studied to predict axillary lymph node status. RESULTS: In a multivariate logistic regression analysis LVI (present v.s. not present), Ki-67 (> or = 18% v.s. < 18%), tumor size (1.1-2 cm v.s. < or = 1 cm), and histologic grade (G3 v.s. G1/2) were identified as independent predictive factors of axillary lymph node metastases. Approximately 13% of patients (n = 47) with well or moderately differentiated tumors less than or equal to 1 cm, no lymph vascular invasion, and a low Ki-67 staining were identified as having a low risk of axillary lymph node metastases of 4.3%. However, 20 patients with all four unfavorable predictive factors had a 75% incidence of axillary lymph node involvement. CONCLUSION: Primary tumor characteristics can be used to identify a subgroup of patients with a low risk of axillary lymph node metastases in T1 breast cancer. Preoperative risk assessment might be used to omit routine ALND in those patients at low risk of axillary lymph node metastases.

Adult↗

Inverse association between melanoma and previous vaccinations against tuberculosis and smallpox: results of the FEBIM study.

Various forms of immunotherapy utilizing bacille Calmette-Guérin vaccine or vaccinia vaccine have been evaluated in clinical trials on melanoma patients. The effect of the "natural" application of these vaccinations, administered to provide protection against tuberculosis and smallpox, has, however, never been studied in epidemiologic investigations on risk factors for melanoma. In a case-control study comprising 11 institutions in seven countries we recruited 603 incident melanoma cases and 627 population controls frequency matched to the cases with respect to sex, age, and ethnic origin within each center to assess this relationship to obtain insights into the prevention of melanoma. Exposure information, incorporating also detailed ascertainment of potential confounding variables, was obtained in standardized personal interviews at the study subject's home. We found an inverse association between melanoma risk and previous bacille Calmette-Guérin vaccine/vaccinia vaccination depicted by an adjusted odds ratio of 0.44 (95% confidence interval: 0.26-0.72) for those vaccinated against tuberculosis and smallpox compared with subjects without a positive history of either vaccination. A variety of subgroup analyses showing a consistent pattern of results make it unlikely that the observed inverse association is a spurious finding. We conclude that bacille Calmette-Guérin vaccination and vaccinia vaccination may lower melanoma risk. Current immunologic theory of melanoma development provides a sound basis for understanding the biologic plausibility of the findings that have to be confirmed in future studies.

BCG Vaccine↗

The spectrum of contact allergy in elderly patients with and without lower leg dermatitis.

BACKGROUND: There is a strong influence of lower leg dermatitis on the spectrum of allergic contact sensitivity in elderly patients. OBJECTIVE: To quantitatively assess the impact of this factor which confounds the age-related pattern of allergic contact sensitivity. METHODS: Stratified analysis of allergic contact sensitivity data collected between 1996 and 1999 in the 32 centres of the Information Network of Departments of Dermatology (three age groups: < or =60, 61-75, > or =76 years), both as crude and as directly standardised (for sex and leg dermatitis) proportions. RESULTS: Among the 36,070 patients tested with the German standard series, allergic contact sensitivity to neomycin, lanolin, cetostearylic alcohols, colophony, fragrance mix and balsam of Peru, among others, was (much) more common in the elderly, with proportions more or less affected by standardisation. CONCLUSION: The comparison of crude and standardised proportions provides evidence that allergic contact sensitivity to several allergens strongly depends not only on age itself, but on age-related and thus confounding co-morbidity.

Age Factors↗

Impact of repetitive manual materials handling and psychosocial work factors on the future prevalence of chronic low-back pain among construction workers.

OBJECTIVES: This study investigated the influence of manual stone and brick handling and psychosocial work factors on the risk of chronic low-back pain and describes the impact in terms of risk advancement period. METHODS: The Hamburg Construction Worker Study included a longitudinal study among 488 male construction workers. Adjusted prevalence ratios (PR) of chronic low-back pain (>3 months during the last 12 months) according to self-reported worktasks in the baseline survey were estimated with the Cox proportional hazards model. RESULTS: The 1-year prevalence of chronic low-back pain was 15.4%. Workers with chronic low-back pain in the baseline survey had a higher risk of such pain during the follow-up (PR4.07,95% CI 2.18-7.59). The prevalence in association with laying large lime sandstones for >2 hours per shift (PR 1.80, 95% CI 1.04-3.14) further increased after adjustment for job category (PR 2.69, 95% CI 1.25-5.78), and it advanced the risk by a risk advancement period of 18 years (95% CI 4-39). Workers with low satisfaction with their work achievements had a higher prevalence of chronic low-back pain (PR 2.07, 95% CI 1.10-3.88). Similar risk estimates were observed in the subgroup without chronic low-back pain in the baseline survey. A strong effect of time pressure wasonly present for these workers (high: P R 6.30,95% CI 1.41-28.21). CONCLUSIONS: The results suggest that repetitive work involving bent positions and the manual manipulation of heavy stones increases the risk of future chronic low-back pain. For risk communication, the notion that a 40-year-old construction worker laying large sandstones has the same risk as an unexposed 58-year-old construction worker may be more informative.

Achievement↗

Uptake of (201)Tl into primary cell cultures from human thyroid tissue is multiplied by TSH.

UNLABELLED: According to current guidelines, (201)Tl scintigraphy aiming at the detection of iodine-negative metastases of differentiated thyroid carcinoma is usually performed during hormone replacement in thyroid-stimulating hormone (TSH)-suppressive doses. The aim of this study was to determine the effect of TSH on thyroid (201)Tl uptake in vitro. METHODS: Adherent monolayers of human thyroid tissue (1.965-3.000 million cells) were cultured after mechanical disintegration and enzymatic digestion by neutral protease. The samples were derived from patients undergoing surgical treatment of nodular goiter. Studies were performed on paranodular tissue components, exclusively. Cells originating from identical tissue samples were dispensed into matched-pair cultures and incubated in parallel by a TSH-free medium and by a medium containing 10 IU/L bovine TSH. Thyroglobulin (Tg) accumulation was calculated after repetitive measurements of Tg concentrations by radioimmunoassay. Uptake studies were initiated by adding fresh medium containing (201)Tl (8.2-91.0 kBq). After 1 h of incubation, the media were removed and the cells were detached by trypsin and collected by centrifugation. Uptake was measured by a gamma-counter, and cellular uptake values were calculated as percentages of total activity normalized to 1 million cells. The statistical significance of differences in Tg release and (201)Tl uptake was corroborated in a generalized estimating equations analysis taking the variability of unbalanced replicate measurements into account. RESULTS: Cells cultured in the presence of TSH displayed a 2-fold release of Tg (12.949 ng/h/million cells vs. 6.049 ng/h/million cells, P = 0.001) and triplicate (201)Tl uptake (0.718%/million cells vs. 0.249%/million cells, P = 0.0002). CONCLUSION: (201)Tl uptake in human thyroid cells is significantly increased by TSH. These data suggest that withdrawal of thyroid hormone substitution has the potential to improve the sensitivity of (201)Tl scintigraphy for detecting thyroid remnants or cancer recurrences. This suggestion should be further investigated in patients and in cell cultures from thyroid carcinomas.

Cells, Cultured↗