Search

One of the potential threats to the effectiveness of the Balanced Scorecard (BSC) is that managers over- or underuse particular perspectives of the BSC. Specifically, we investigate the effects of (1) the presentation of strategic objectives (generic strategy map versus strategic objective list), and (2) the performance outcome patterns (positive versus negative outer perspective) across the performance measurement perspectives of the BSC and find support that is consistent with the violation of the causal independence assumption (VCIA) in the psychology literature (Rehder 2014). Our findings show that the presentation of the strategic objectives and the performance outcome patterns interact significantly affecting performance evaluation outcomes. Two follow-up experiments provide further support for the VCIA observed in the main experiment by ruling out an alternative explanation that managers simply place a greater emphasis on financial performance measures. Data Availability: Data are available from the authors upon request.

Based on morphological characteristics, two subspecies of the Transcaucasian rat snake (Zamenis hohenackeri) are currently recognized, namely Z. h. tauricus and Z. h. hohenackeri. Both subspecies are repeatedly considered to be conspecific colour morphs, or have even been confused with Z. situla. Although, few studies involved the Transcaucasian rat snake in a phylogenetic approach, none has so far led to any taxonomic changes. We assessed the intraspecific morphological variation and phylogeographic relationships among specimens from different locations across its updated distribution. Our molecular (1191 bp mtDNA, 565 bp nuDNA) and morphological data provide sufficient evidence to support three distinct lineages within the Z. hohenackeri complex with a different arrangement compared to a previous study. These represent the subspecies Z. h. hohenackeri, Z. h. tauricus, and a lineage from southwestern Turkey which is described as a new subspecies. Aspects of historical biogeography and conservation status are briefly discussed.

There is a debate in the literature as to whether employee selection is a substitute or complement to incentive contracting. We argue that incentive contracts and selection can be both complements and substitutes conditional on the contracting difficulty faced by the firm. We examine these control choices in a setting where contracting difficulties arise due to the firm's choice of strategy and from the volatility created by the firm's external environment. We select a firm's commitment to organizational learning (OL) as our strategic choice variable as this provides a useful proxy for identifying settings where explicit incentive contracting is difficult. The results show that, as firms become increasingly committed to OL, incentive contracts and employee selection operate as complements. However, with a high commitment to OL and an increasing level of external volatility, contracting on performance measures will become less effective. In this context, our results indicate that there is a substitution effect toward employee selection.

Some organizations have begun to target their goal-setting method more closely to the ability levels of their employees. In this article, we report the results of a laboratory study of 138 undergraduate students, which shows that these “ability-based” goals are more effective at improving performance than a “one goal for all” approach, where everyone is assigned the same performance target. Results from repeated measure tests and other analysis of variance tests show that lower-ability individuals in the ability-based goal condition outperform those in the one goal for all condition. Lower- and moderate-ability participants in the one goal for all condition also experienced larger decreases in performance in later rounds.

Few herpetological contributions, all published prior to 1875, list Zamenis persicus Jan, 1863 (type material lost) as valid; a couple of contemporary and later references consider this Racer name a junior synonym of Turano-Sindian taxa of the genus Platyceps Blyth, 1860. Coluber longissimus var. persica Werner, 1913 is a Ratsnake species currently referred to Zamenis Wagler, 1830. For the sake of taxonomic stability, we reject Z. persicus Jan (nomen oblitum) under the provisions of Article 23.9.2 (Reversal of precedence) of the ‘Code’ (ICZN 1999) and declare the secondary homonym Z. persicus (Werner) as the valid name for the Persian Ratsnake. (© 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

This study examines factors influencing the difficulty of self-set goals and performance in a setting where employees were able to choose their performance goal from a menu of three choices established by management. Rewards for goal attainment were increasing in the difficulty of the goal. We develop a behavioral model of the factors expected to affect employees’ goal choices and performance. Anticipated influences on goal difficulty include employees’ impression management intentions, past performance, experience, and prior eligibility for rewards. We also expect performance to be related to goal difficulty. We use a unique combination of archival and questionnaire data from 476 employees at several call centers of a financial services company to test our hypotheses. All predictions are supported: the difficulty of self-set goals is negatively associated with employees’ impression management intentions; employees with better past performance set more difficult goals; and both prior performance and goal difficulty are positively associated with current period performance. We conduct supplementary analysis examining the extent to which employees selected attainable goals and the impact this had on performance. We also analyze the extent to which ratcheting concerns may have influenced actual performance for those employees who attained their goal. Implications for future research and practice are discussed.

This study closes the circle on a series of studies which have examined cross-cultural differences in the likelihood of sharing information in a situation where an error has been made. Building on the work of Chow et al. (1999), Chow et al. (2000), Salter and Schulz (2005), and Salter et al. (2008) it seeks to control for collectivism and test the effect of face by using nations that are quite similar in terms of collectivism, but at opposite ends of the face dimension. It finds that Chinese managers are less willing to share negative information when the supervisor is present than Chilean managers. Once the supervisor is removed there is no significant difference in the information sharing pattern of these two cultures. We attribute the results to the effect of “face” in the Chinese culture, which suppresses information sharing willingness in Chinese managers when the supervisor is present and is not a facet of the Chilean culture.

One of the biggest assets of a firm is its information base. Included in this information base is a knowledge of prior errors and failures. Extant research suggests that while the propensity to share “bad news” (i.e. a prior error) is dependent on the cost of sharing, the perceived value of that cost may be culturally dependent. One area of interest that has received substantial attention in the prior literature has been cross-cultural differences in negative information sharing in general, as well as the particular context in which the individual's superior is either present or absent during the information-sharing process. Our study examines the role of the two cultural values (individualism/collectivism and to a lesser extent power distance) in explaining national differences in information sharing. By focusing on a sample from Chile and Australia, we were able to remove the regional cultural dimension of face, which has been inherent in prior studies that used Greater China as the representative of a collectivist society. Results from our quasi experiment show that when a supervisor is present during information sharing, collectivist Chilean decision-makers are more willing to share negative information with their colleagues than their counterpart and individualist Australian decision-makers. Our results also show that when a supervisor is absent, both Australian and Chilean decision-makers are willing to share more negative information but the increase in the Australian propensity is significantly greater than that of the Chileans.

Improvements in the life expectancy of women with breast cancer raise important questions how to improve quality of life (QoL) for women sustaining complications and side effects of cancer treatment. The presented study examined the prevalence of arm morbidity in a cohort of primary breast cancer patients over time as a result of the extent of axillary lymph node dissection. Of particular interest is the question of using a recognized QoL assessment instrument at defined assessment points as an endpoint criteria of oncological treatment.A prospective, population-based, longitudinal cohort study of patients with primary breast cancer was performed (n = 389). QoL data (EORTC QLQ C30 + BR23) and clinical data were assessed at designated time points. Primary endpoint of this analysis was patient reported arm morbidity assessed with the three-idem scale in the BR 23 (swelling, moving, pain).20% of the patients evidenced considerable impairments in arm functioning. Arm morbidity was significantly related to the number of lymph nodes dissected (P0.002 entire cohort, P0.001 lymph node negatives) and was independent of age, stage of the disease, kind of breast surgery and radiation treatment. Early impairments in arm functioning (below 50 score values) assessed within 6 months after axillary surgery was a good predictor for late arm morbidity at 12 months RR 11.5 (CI 95% 4.7-28.4), 24 months RR 6.0 (CI95% 2.8-13.3) and 36 months RR 3.8 (CI 95% 1.8-7.9).Arm morbidity after axillary surgery is a severe and chronic condition affecting many breast cancer patients. The recognized QoL assessment instrument depict patients with severe impairments in arm functioning after axillary lymph node dissection and predict late arm morbidity. To increase patients' quality of life it thus may serve as a valid assessment tool for screening, allowing early referral for treatment and monitoring.

This paper proposes that a strong ethical environment will be effective in reducing the tendency for managers to continue failing projects in both the presence and absence of agency problems. The findings support these propositions, with a strong ethical environment found to significantly reduce managers' tendency to continue failing projects. Also, while agency problem effects were still present under a strong ethical environment, their impact was similar to the case of a weak ethical environment in the absence of agency problems. These findings suggest that creating a strong ethical environment may be a highly desirable control option for organizations generally.

Some research has suggested multiple-format accounting feedback in an attempt to accommodate varying cognitive information processing styles (Gardner and Martinko 1996). This costly information solution, however, has not been widely adopted in practice. An alternative approach, which fits nicely with current team-orientation practices in the work place, is to create combinations of workers. These work groups can bring to bear varying cognitive styles in solving complex business problems using accounting information. This study explores how cognitive style diversity affects the decision quality performance of dyads for a complex decision task. An experiment was performed to extend prior accounting studies into perception differences based on the sensor/intuitive dimension of the MBTI (Myers-Briggs Type Indicator) instrument, and how such differences affect users of performance reports in their decision-making processes. In this study, subjects were classified into sensor or intuitive dyad members, based on the Myers-Briggs MBTI instrument, and engaged in a task that involved a series of simulated production decisions with nonfinancial direct performance feedback. After controlling for task conflict, results showed significantly better decision performance for cognitively diverse dyads over homogeneous sensor dyads. Similar performance differences, however, were not observed between cognitively diverse dyads and homogeneous intuitive dyads. Task conflict was not significant in explaining differences in decision performance. The findings could have implications in the areas of management control system design and personnel management.

This study proposes that organizations should consider project hurdle rates, as part of their control system design, to reduce escalation of commitment behavior in managers. In particular, we empirically examined the escalation of commitment tendencies in managers receiving organization-set, self-set, and no hurdle rates.Consistent with prior expectations, we found self-set hurdle rates to be an effective control mechanism resulting in significantly lower levels of escalation of commitment. Contrary to expectations, however, organization-set hurdle rates were not effective. Self-set hurdle rates also resulted in significantly higher cut-off rates compared to the average return of the investment portfolio held by the managers.As escalation of commitment has been recognized as a serious potential problem in organizations, the use of self-set hurdle rates is a step toward reducing the level of escalation tendencies in managers.

This cross-sectional study updated age changes for ultrasonometry (QUS) of the os calcis in a large sample of healthy German women. The speed of sound (SOS), broadband ultrasound attenuation (BUA), and stiffness index (SI) of the os calcaneus were measured in 5148 women (mean age 55.2 ± 10.6 yr) using the Achilles ultrasonometer (GE/Lunar). There was an overall decline of 16% for BUA, 4% for SOS, and 32% for SI between late adolescence and old age. In premenopausal women, BUA decreased only slightly (–2%), whereas postmenopausal women showed a significantly increased decline (–12%). In contrast, SOS continuously decreased from the age of 15; there was a decline of 2% from adolescence to menopause. The SI of premenopausal women decreased only by 9%, but the postmenopausal decline of almost 21% was significantly greater. In accordance to our previous report, the age regression for SI in the larger sample differed from the earlier sample, indicating an increased bone loss with aging after the menopause. The SI values in premenopausal German women were comparable to those for British and American women 20–50 yr of age. After age 50, the SI of German women was significantly 3–7% higher in comparison to the British and American reference population.

Die Osteoporose zahlt mit ca. 5–6 Mio. Betroffenen zu den haufigsten Erkrankungen der postmenopausalen Frau in Deutschland. Hierbei sind Gynakologen gemeinsam mit Orthopaden, Endokrinologen und Radiologen mit der Diagnostik der Erkrankung betraut. Neben Anamneseerhebung und korperlicher Untersuchung stehen mit den radiologischen osteodensitometrischen Verfahren sowie den Ultraschallverfahren eine Vielzahl von Methoden zur Verfugung, die in Bezug auf die Frakturpradiktion ebenburtig sind. Da ca. 80–90% der Osteoporosefalle der Frau durch den Abfall der ovariellen Ostrogenproduktion in der Postmenopause bedingt sind, fallt der Gynakologie die wichtigste Rolle bei der Osteoporosepravention zu, die bereits in der ersten Dekade nach der Menopause begonnen werden sollte. In Abhangigkeit vom individuellen Risikoprofil besteht die Moglichkeit einer Pravention/Therapie durch eine knochenstoffwechselgesunde Lebensfuhrung/Ernahrung, ggf. Kalzium und Vitamin-D-Supplementierung, der Einleitung einer Hormonersatztherapie bzw. einer Behandlung mit selektiven Ostrogenrezeptormodulatoren (SERM), Bisphosphonaten oder Fluoriden.

The multifactorial disease of osteoporosis is one of the most frequent diseases, affecting about 5 - 6 Mio. postmenopausal women in Germany, today. In spite of the introduction of new technologies of fracture risk assessment and new pharmacological opportunities the incidence of fracture is still increasing. Therefore, early identification of women at high risk as well as early and individualised preventive measures are essential in the prevention of osteoporosis. Changes of dietary habits as well as lifestyle including an increase in physical activity are of up most importance. In addition to Calcium and Vitamin D supplementation, hormone replacement therapy (HRT) is accepted as the first line and cost effective pharmacological treatment for the prevention of osteoporosis. Numerous cross sectional, case-control and prospective studies showing the effect of HRT on bone reabsorption and bone mineral density (BMD) have been published. HRT reduces bone turnover which is followed by an increase of BMD. A number of case-control and cohort studies as well as a few recent prospective studies have been investigating the effect of HRT on osteoporosis related fracture. These studies confirm that HRT leads to a significant decrease of osteoporosis related fracture (Hip fracture by > 25%). However, randomised, prospective studies are needed to underline the effect on osteoporosis related fracture. Although the effect of HRT on BMD is independent of both, the age at which treatment is started and the route of administration, a dose-response relation as well as a greater response in patients with a lower initial BMD has been reported. Since bone is lost rapidly when treatment is stopped, the duration of treatment is clinically important in evaluating the effect of HRT on BMD. Hereby, a duration of 10 years and more seems desirable. Since the ongoing controversial discussion on the duration dependent increase of the incidence of breast cancer and the discussion on secondary prevention of cardiovascular disease, any therapy decision must be individually evaluated. The following article gives a systematical review on the recent literature regarding the influence of HRT on BMD and osteoporosis related fracture.

In this study we examine the effects of personal responsibility and information asymmetry on managers’ tendencies to escalate their commitment to poorly performing investment projects. Consistent with the recommendations by critics of the escalation literature (e.g. Bowen, 1987), we provided subjects with unequivocal negative project feedback. However, counter to other recent conflicting studies adopting Bowen’s recommendations, we reverted back to Staw’s (1976) original methodology and incorporated “free-choice” into our personal responsibility construct. Our results confirm Staw’s (1976) original proposition of a positive relation between a manager’s personal responsibility for a poorly performing project and his/her subsequent escalation of commitment to the project. Further, we proposed that information asymmetry moderates the relation between the level of personal responsibility and escalation of commitment. Our results did not confirm this proposition. As such, results from our study re-establish personal responsibility as an important antecedent variable to escalation of commitment.

Studies from six regions of Germany (Aachen (W1), Dresden (E1), Jena (E2), Marburg (W2), Munich (W3), and Stuttgart (C1)) have been compared to verify and assess the quality of healthcare using breast cancer as an example. All of the data collection was carried out in comprehensive cancer centres and is population-based, with the exception of C1. Classic prognostic factors and the initial treatment of 8661 women with breast cancer, diagnosed between 1996 and 1998, were examined. Primary therapy, breast conserving therapy (BCT), and the use of subsequent local radiation and/or systemic therapy (chemotherapy or hormonal therapy) were analysed. BCT was performed on 39.3–57.7% of patients. By pT-category, the proportion of BCT in the six regions were as follows: for pTis between 37.8 and 64.3%, for pT1 between 51.7 and 71.5%, for pT2 between 25.9 and 51.1%, for pT3 between 0 and 13.1% and for pT4 between 0 and 15.2%. Multivariate analyses, adjusted for age and biological factors, showed a significant influence of the treating hospital on the mastectomy rate. The use of radiotherapy after BCT (80%) was quite homogeneous in the six regions. The application of radiotherapy after mastectomy, however, varied between 10.4 and 32.2%. In all regions, for premenopausal patients, the use of adjuvant systemic therapy almost reflected the St. Gallen-Consensus recommendations. In contrast, post-menopausal women with positive lymph nodes were not always treated according to these standards. In all regions, age had an influence on the administration of treatment: elderly breast cancer patients received less BCT, less radiotherapy and less adjuvant therapy than recommended in the St. Gallen-Consensus. Feedback of the results was made available to each hospital, providing a comparative summary of patient care that could be used by the participating hospitals for self-assessment and quality-control.

Several recent reports have demonstrated the expression of luteinizing hormone-releasing hormone receptors by human ovarian and endometrial cancers. Controversy persists on the relevance of this finding, in particular whether these receptors mediate direct antiproliferative effects of luteinizing hormone-releasing hormone analogues. We correlated the expression of luteinizing hormone-releasing hormone receptors by well-characterized ovarian and endometrial cancer cell lines with the ability of luteinizing hormone-releasing hormone analogues to reduce their proliferation and studied the autoregulation of luteinizing hormone-releasing hormone receptor expression by luteinizing hormone-releasing hormone agonist triptorelin and antagonist cetrorelix. The expression of luteinizing hormone-releasing hormone receptors was assessed in a series of specimens from primary ovarian and endometrial cancers.Luteinizing hormone-releasing hormone receptor expression was assessed by semiquantitative reverse transcriptase-polymerase chain reaction and radioligand binding assay. Antiproliferative effects were ascertained by proliferation assays in the absence or presence of luteinizing hormone-releasing hormone analogues.Ovarian (4/6 cell lines) and endometrial (5/6 cell lines) cancer cell lines expressed luteinizing hormone-releasing hormone receptors. The proliferation of these luteinizing hormone-releasing hormone receptor-positive cell lines was dose- and time-dependently reduced by agonistic and antagonistic luteinizing hormone-releasing hormone analogues. Luteinizing hormone-releasing hormone receptor density was reduced to 80% of controls (control, 100 %; P.001) by luteinizing hormone-releasing hormone analogues. Seventy percent of primary ovarian cancers and 83% of primary endometrial cancers expressed luteinizing hormone-releasing hormone receptors.These findings suggest that luteinizing hormone-releasing hormone receptors that are expressed by human ovarian and endometrial cancer cell lines mediate direct antiproliferative effects of luteinizing hormone-releasing hormone analogues. Because most respective primary cancers expressed luteinizing hormone-releasing hormone receptors, these receptors might be used for novel antiproliferative therapeutic approaches and should be further evaluated.

Zusammenfassung Sowohl endogene als auch exogen zugefuhrte Hormone haben Auswirkungen auf die Gewebsdichte der weiblichen Brust und somit auf die Sensitivitat und Spezifitat der Mammographie. Bei intakter Ovarialfunktion sollte eine Mammographie daher in der Follikelphase durchgefuhrt werden. Auch eine postmenopausale Hormonersatztherapie beeinflusst die Gewebsdichte, insbesondere bei kontinuierlicher kombinierter Gabe von Ostrogenen und Gestagenen. Dagegen erhohen Tibolon und Antiostrogene die Gewebsdichte nicht. Da bislang nicht geklart ist, welchen Einfluss eine Verminderung der mammographischen Gewebsdichte auf das Brustkrebsrisiko hat, ist sie als Biomarker in der Pravention des Mammakarzinoms nicht geeignet. Bei der Krebsfruherkennung ist die individuelle endokrine Situation der Frau in die Bewertung der Befunde mit einzubeziehen. Unklare Befunde bedurfen der weiteren apparativen oder minimal invasiven Abklarung.

Objective: Reproductive factors such as parity and breast-feeding may be associated with low bone mass and osteoporotic fractures in later years. In this study, os calcis quantitative ultrasonometry was used to elucidate the relationship between parity, lactation and bone mass in postmenopausal women. Design: This was a comparison study using subsequent matched pairs analysis as well as multiple linear regression analysis. The study was carried out at five centers in Germany. The study included 2080 postmenopausal women (age (mean ± SD) 58.8 ± 8.2 years), who were attending for routine check-up and in whom diseases and drug treatments known to affect bone metabolism had been excluded. Methods and outcome measures: Women underwent quantitative ultrasonometry (QUS) measurement at the heel. Values of the ultrasonometry variables –speed of sound, broadband ultrasound attenuation and stiffness index –were calculated and compared for nulliparous and parous women and for women who had and had not breast-fed. Bec...

Zusammenfassung In der frauenspezifischen Gesundheitsversorgung in der Bundesrepublik Deutschland steht das Thema "Brustkrebs" an erster Stelle. Senkung der Sterblichkeit bei Brustkrebs, die Verbesserung der Heilungschancen unter Erhalt der Lebensqualitat fur betroffene Frauen sind das definierte Gesundheitsziel. Erreicht werden kann dies durch eine qualifizierte, flachendeckende, fach- und sektorubergreifende leitlinienkonforme Ausgestaltung der 3 Saulen der Versorgungskette: sekundare Pravention, Therapie und tertiare Pravention. Funf Masnahmen umfassen heute die zielorientierte, regelmasige Tumornachsorge: Fruherkennung von lokal, lokoregionarem und kontralateralen Rezidiven, Kontrolle und Verbesserung der Therapiefolgestorungen Psychologische Betreuung, Beistand zur optimalen Gesundung, Lebensqualitat und Selbstbestimmung. Eine dauerhafte und zeitnahe Verbesserung einer an der Lebensqualitat der Patienten orientierten Versorgungsstruktur ist dabei masgeblich an die positive Bereitschaft der zielorientierten Forderung durch die Kostentrager gebunden.

Zusammenfassung Die Osteoporose zahlt mit 5–6 Mio. Betroffenen zu den haufigsten Erkrankungen der postmenopausalen Frau in der BRD. Mit osteodensitometrischen Verfahren wie der dualen Rontgenabsorptiometrie (DXA), der quantitativen Computertomographie (QCT) sowie der quantitativen Ultrasonometrie (QUS) stehen verschiedene Methoden zur Verfugung, die in Bezug auf die Frakturpradiktion ebenburtig sind. In ca. 80–90% ist die Osteoporose durch den physiologischen Abfall der ovariellen Ostrogenproduktion in der Postmenopause bedingt. Da der Knochenmasseverlust im ersten Jahrzehnt nach der Menopause am starksten ausgepragt ist, sollte bereits zu diesem Zeitpunkt mit der Osteoporoseprophylaxe begonnen werden. Durch gezielte Diagnostik kann ein individuelles Risikoprofil erstellt werden. In Abhangigkeit der Untersuchungsergebnisse besteht dann die Moglichkeit einer Pravention oder Therapie. Neben einer knochenstoffwechselgesunden Lebensfuhrung und Ernahrung bestehen die Optionen einer Kalzium- und Vitamin-D-Substitution, der Einleitung einer Hormonersatztherapie bzw. einer Behandlung mit selektiven Ostradiolrezeptormodulatoren, Bisphosphonaten oder Fluoriden.

Grundlagen: Die vorliegende Studie wurde durchgefuhrt, um die Rate der falsch-negativen Befunde der ultraschallgestutzten Stanzbiopsie (CNB) zu erheben und zu untersuchen, inwieweit die immunhistochemische Analyse der falsch-negativen Stanzbiopsate mit dem Epithelial-Membrane-Antigen eine Hilfe bietet, Karzinomzellen zu detektieren.

Die multifaktorielle Erkrankung der Osteoporose zahlt heute zu den haufigsten Erkrankungen der postmenopausalen Frau und weist trotz eines erweiterten Spektrums diagnostischer und therapeutischer Moglichkeiten weiterhin eine zunehmende Inzidenz auf. Die Osteodensitometrie ist inzwischen die anerkannte Methode zur Beurteilung des individuellen Frakturrisikos und klinisch unerlasslich im Rahmen einer Osteoporosediagnostik. Die radiologischen Verfahren wie die duale Rontgenabsorptiometrie (DXA) und die quantitative Computertomographie (QCT) sind den Ultraschallverfahren, wie die quantitative Ultrasonometrie (QUS), in Bezug auf die Frakturpradiktion ebenburtig. Die Messwerte der Osteodensitometrie werden nicht mehr in Prozenten angegeben, da diese zwischen den einzelnen Verfahren nicht vergleichbar sind, sondern als T- oder Z-Werte. Die Methoden korrelieren untereinander im Mittel zu ca. 70 %. Dabei ist jedoch die Hohe der Korrelation fur den einzelnen Patienten unerheblich. Hier ist es vielmehr entscheidend, diskrepante bzw. konkordante Werte fur den Patienten im Sinne der Fragestellung richtig zu interpretieren. Diskrepanzen zwischen zwei Messungen beim gleichen Patienten entstehen durch Fehlinterpretation der Messwerte verschiedener Methoden, die durch die Variabilitat der Anteile von Kompakta und Spongiosa im menschlichen Skelett an unterschiedlichen Messstellen und den unterschiedlichen Einflussen von Messtechnologie und Biologie bedingt sind.

Objective: Quantitative ultrasonometry is a radiation-free, low-cost, simple, quick and mobile method to evaluate properties of bone. The objective of this study was to evaluate the effectiveness, reliability and age-related findings of this technique in women and to establish a reference database. Methods: In a cross-sectional study we measured speed of sound, broadband ultrasound attenuation and the stiffness index of the calcaneus in 2272 women (mean age, 53.0 ± 10.5 years) with an ultrasound bone densitometer. Women with a history of osteoporosis, osteoporosis-related fractures or those using medications known to affect bone metabolism were excluded. In 791 women both calcanei were studied. Results: The short-term precision in vivo, expressed as coefficient of variance, was 1.2% for broadband attenuation, 0.2% for speed of sound, and 1.3% for stiffness. In women in whom both calcanei were studied the coefficient of correlation was 0.92 for speed of sound (p

Die Publikationen der Danish Breast Cancer Cooperative Group und die Ergebnisse des British Columbia Trial haben zu erheblichem Diskussionsbedarf uber den Stellenwert der Strahlentherapie nach Mastektomie gefuhrt. Ganz unterschiedliche Vorgehensweisen findet man selbst innerhalb derselben Tumorzentren. Die Deutsche Gesellschaft fur Senologie, in der alle medizinischen Bereiche auf dem Gebiet des Mammakarzinoms interdisziplinar kooperieren, hat deshalb eine gemeinschaftliche Stellungnahme erarbeitet. Material und Methode: Als Beratungsgrundlage dienten aktuelle Literaturmitteilungen und Expertenmeinungen, insbesondere die seit 1997 publizierten randomisierten Studien, ds weiteren Metaanalysen der Early Breast Cancer Trialists' Collaborative Group, epidemiologische Untersuchungen zum zeitlichen Verlauf von Fernmetastasen beim Mammakarzinom sowie die aktuelle Konsensbildung der American Society for Therapeutic Radiology and Oncology. Ergebnisse des Konsens: 1. Die optimale Durchfuhrung der Mastektomie ist eine wichtige Voraussetzung fur die Tumorheilung. Dabei sind sowohl eine R0-Resektion des Tumors als auch eine Entfernung von zumindest zehn Lymphknoten aus Level I und II der Axilla anzustreben. Bei axillarem Lymphknotenbefall stellt die operative Entfernung der Achsellymphknoten nicht nur eine diagnostische, sondern auch therapeutische Masnahme dar, indem damit das Risiko fur ein lokoregionares Rezidiv vermindert wird. 2. Lokoregionare Rezidive sind wahrscheinlich nicht nur Indikator, sondern auch Quelle fur das Auftreten von Fernmetastasen. 3. Die Bestrahlung der Brustwand und der Lymphabflusswege erhoht bei Risikopatientinnen die Heilungswahrscheinlichkeit und vermindert das Risiko eines lokoregionaren Rezidivs. Sie verbessert auch bei Resttumor oder inkompletter Achselausraumung die Prognose. Gesicherte Indikationen zur postoperativen Radiotherapie nach Mastektomie sind: T3/T4-Karzinome, T2-Karzinome mit einer Grose > 3cm, multizentrisches Tumorwachstum Lymphangiosis carcinomatosa oder Gefaseinbruche, Befall der Pektoralisfaszie oder Sicherheitsabstand < 5mm, R1- oder R2-Resektion, mehr als drei befallene Achsellymphknoten. Als sinnvolle, aber noch nicht in klinischen Studien evaluierte Indikationen gelten: Multifokalitat, extensive intraduktale Komponente, Rezeptornegativitat, Malignitatsgrad G3, diffuse Mikrokalzifikationen, ein bis drei axillare Lymphknotenmetastasen. Zustand nach mehreren, nicht in sano erfolgten Biopsien. Alter unter 35 Jahre. 4. Eine simultan zur Radiotherapie durchgefuhrte Tamoxifenbehandlung ist entgegen teilweise anderslautenden In-vitro-Daten durchaus sinnvoll, zumal Tamoxifen die Apoptose fordert. Eine CMF-Therapie wird ublicherweise im Sandwich-Verfahren durchgefuhrt, kann jedoch in begrundeten Fallen auch simultan zur Strahlentherapie erfolgen. Eine anthrazyklinhaltige Chemotherapie sollte hingegen vor Beginn der postoperativen Radiotherapie abgeschlossen sein. Schlussfolgerungen: Die adjuvante Radiotherapie nach Mastektomie verbessert zumindest bei Risikopatientinnen die Zehn-Jahres-Uberlebenswahrscheinlichkeit um bis zu 10%. Die Hypothesen von Halsted und Fisher schliesen sich gegenseitig keineswegs aus. Es gibt Patientinnen, bei denen eher die eine, und solche, fur die eher die andere Hypothese Gultigkeit hat.

This study aimed to evaluate the influence of hormone replacement therapy (HRT), the estradiol concentration and body mass index (BMI, kg/m(2)) on the serum leptin concentration in postmenopausal women.352 healthy postmenopausal women (mean age, 60.9 +/- 8.5 years) participated in this comparative study. 71 (30%) women (mean age 55.9 +/- 8.3 years) had taken HRT, while 281 (70%) women (mean age, 59.1 +/- 10.6 years) had not. Baseline characteristics -age, weight, height, BMI (greater than or = 25 or25), follicle stimulating hormone, estradiol, and leptin values-were compared in the two groups. In a second analysis to evaluate the influence of HRT, estradiol concentrations, and BMI on leptin concentrations, these data were analysed in women allocated to one of four groups: (a) postmenopausal women not on HRT with a BMI25 (n = 130); (b) postmenopausal women not on HRT with a BMI greater than or = 25 (n = 151); (c) postmenopausal women on HRT with a BMI25 (n = 48); and (d) postmenopausal women on HRT with a BMI greater than or = 25 (n = 23). Leptin concentrations were subsequently analysed in relation to BMI and age and BMI and estradiol concentrations to determine any independent effect of these variables.The women taking HRT had a significantly lower mean age, weight, BMI and follicle stimulating hormone concentration than those who were not taking HRT. Furthermore, they had a higher mean height and serum estradiol value, but a significantly lower serum leptin concentration. After controlling for BMI, neither the use of HRT nor the estradiol concentration was found to be related to the leptin value (group (a) versus (c) and group (b) versus (d)), but there were significant differences in leptin concentrations between HRT users with BMI greater than or = 25 and BMI25 and between women not taking HRT with BMI greater than or = 25 and BMI25 (groups (a) versus (b) and (c) versus (d)). Furthermore, women with a BMI greater than or = 25 had significantly higher leptin concentrations than women with a BMI25, irrespective of the HRT use.Leptin concentrations are significantly higher in obese postmenopausal women than in their non-obese counterparts. Serum leptin concentrations are not influenced by HRT use or estradiol concentrations. Further studies are needed to elucidate the role of HRT and estrogen on serum leptin concentrations.

Objectives. Spontaneous and epidermal growth-factor-induced proliferation of human gynecological cancer cell lines is dose- and time-dependently reduced by treatment with the luteinizing hormone–releasing hormone (LHRH) agonist triptorelin and antagonist Cetrorelix. This antiproliferative activity is probably directly mediated through the LHRH receptors expressed by the tumor cells interacting with growth-factor-dependent mitogenic signal transduction. We have examined whether epidermal growth-factor (EGF)-induced expression of the early response gene c- fos is reduced by LHRH analogs. Methods. Human endometrial (Ishikawa, Hec-1A), ovarian (EFO-21, EFO-27, SK-OV-3), and breast cancer cell lines (MCF-7) were rendered quiescent by incubation (72 h) in the absence of fetal calf serum and phenol red. This was followed by a 15-min incubation in the absence or presence of the LHRH agonist triptorelin (100 nM) or the antagonist Cetrorelix (100 nM) before the cells were stimulated for 10 min with EGF (100 nM). C- fos mRNA expression was determined by semi-quantitative RT-PCR using a synthetic DNA fragment as internal standard. C-Fos protein synthesis was determined by SDS–PAGE and semi-quantitative Western blotting. Results. In cells derived from endometrial and ovarian cancer, maximal c- fos mRNA expression (seven- to ninefold over basal level) was obtained 30 min after EGF stimulation. In the breast cancer cell line MCF-7 this effect was obtained 60 min after EGF treatment. In all of the lines expressing LHRH receptor, EGF-induced c- fos mRNA expression as well as c-Fos protein synthesis was dose-dependently reduced by treatment with LHRH agonists and antagonists. At 100 nM concentrations of the LHRH analogs, c- fos expression was reduced to baseline levels. No effect of LHRH analogs on EGF-induced c- fos expression was observed in the ovarian cancer cell line SK-OV-3, which does not express the LHRH receptor. Conclusions. These results suggest that the binding of LHRH agonists and antagonists to their receptors inhibits the mitogenic signal transduction pathway of the EGF receptor in endometrial, ovarian, and breast cancer cell lines. The coupling of both signal transduction systems mediates the antiproliferative effect of LHRH analogs.

For N2O, the results of STO-6G calculations indicate that a valence-bond structure I with a π electron configuration R[πx(NO)]1[πx(O)]1[πy(NO)]1[πy(O)]1, in which R = [πx(NN)]2[πy(NN)]2, generates a lower energy than does resonance between two valence-bond structures, II and III, with π electron configurations R[πx(NO)]2[πy(O)]2 and R[πy(NO)]2[πx(O)]2, respectively. In each of these three structures, the central nitrogen atom is apparently pentavalent. A similar conclusion is obtained from the results of the corresponding calculations for isoelectronic HCNO, with R = [πx(CN)]2[πy(CN)]2. Using HCNO + HCCH → isoxazole as the example, valence-bond representations for 1,3-dipolar cycloaddition reactions are compared using the above types of valence-bond structures. For N2O, the bond orders that are implied by structure I, but not those by structures II and III, are shown to be in qualitative accord with the observed bond lengths. The energy for structure I is also calculated to lie below that for a R[πx(NO)]2...

Die Hormonersatztherapie (HRT) fuhrt bis zu einer Anwendungsdauer von 5 Jahren zu keiner Erhohung des Mammakarzinomrisikos. Langere Therapiezeiten erhohen das Risiko geringgradig. Obwohl der Nutzen einer langfristigen HRT nach dem derzeitigen Kenntisstand uberwiegt, muss dieser Faktor im Rahmen der Aufklarung der Patientinnen berucksichtigt werden. Nach der Therapie des Mammakarzinoms gilt die HRT als grundsatzlich kontraindiziert. Im Individualfall kann sie jedoch nach Ausschopffung der Alternativen eingesetzt werden. In der Praxis betrifft dies vorwiegend die Gruppe von Patientinnen, die massiv unter den vegetativen und vasomotorischen Symptomen des Ostrogenentzugs leiden. In dieser Situation sind nicht-hormonale Alternativen meist wenig wirksam.

OBJECTIVE: More than 80% of human ovarian cancers express LHRH and its receptor. The proliferation of human ovarian cancer cell lines is reduced by both LHRH agonists and antagonists. This study was designed to further clarify the possible biological function of this LHRH system. DESIGN: As LHRH agonists and antagonists uniformly reduce proliferation of human ovarian cancer in a dose-dependent way, the effect of low concentrations of authentic LHRH was studied. In addition, longer periods of treatment (up to 9 days) were analyzed. To assess the physiological role of LHRH produced by ovarian cancer cells it was neutralized by adequate concentrations of a specific LHRH antiserum. METHODS: Human ovarian cancer cells EFO-21 and EFO-27, which express LHRH and its receptor, were incubated for 1-9 days with increasing concentrations (1pmol/l to 10 micromol/l) of authentic LHRH or with concentrations of LHRH antiserum capable of neutralizing at least 1nmol/l LHRH. Proliferation was assessed by counting cells. RESULTS AND CONCLUSIONS: Authentic LHRH reduced time- and dose-dependently proliferation (by maximally mean+/-s.e.m. 32.7 +/- 4.4%, Newman-Keuls, P < 0.001) of both ovarian cancer cell lines. At very low concentrations (1pmol/l) a marginal reduction of proliferation or no effect was observed. A mitogenic effect of authentic LHRH was never detected. Treatment of ovarian cancer cell cultures with antiserum to LHRH significantly increased (up to mean+/-s.e.m. 121.0 +/- 2.8% of controls, Newman-Keuls P

This study was undertaken to evaluate the impact of hormone replacement therapy on results of quantitative ultrasonometry of the heel.A total of 2006 healthy perimenopausal women (mean age, 52.2 (10.3 years) were recruited in 5 German centers: 611 women (30%) had received hormone replacement therapy and 1395 (70%) had not. About 90% of the hormone replacement therapy users were current users, and the rest had stopped6 months before the study. Speed of sound, broadband ultrasonographic attenuation, and the stiffness index were compared among the following groups: all users and nonusers of hormone replacement therapy, hormone replacement therapy users and nonuser control subjects matched for age and body mass index, and hormone replacement therapy users grouped in relation to the duration of hormone replacement therapy use and age and control subjects matched for body mass index.Women who were using hormone replacement therapy had significantly higher values (P.001) than did nonusers for all ultrasonographic variables, even after we controlled for age and body mass index. Women who had used hormone replacement therapy for3 years had significantly higher values (P.001) than did matched control subjects for all variables. Differences increased with the duration of hormone replacement therapy use.Quantitative ultrasonometric measurement at the heel differentiates hormone replacement therapy users from nonusers, reflects duration of hormone replacement therapy use, and could be useful in both clinical trials and patient management.

Objective To investigate whether imprint cytology of core needle biopsy (CNB) specimens from breast lesions is a useful method of rapidly obtaining additional diagnostic information and potentially can be used to reduce the number of biopsies needed. Study design Cytologic analysis was performed on 173 breast lesions and compared with their histopathologic diagnoses (143 malignant and 30 benign). For imprint cytology, one CNB specimen was rolled between two slides and stained with Diff-Quik and Papanicolaou stain. Results The diagnostic overall accuracy of Diff-Quik stain (Papanicolaou stain) was 95.4% (95.9%), with a sensitivity of 96.5% (97.2%), specificity of 90% (90%), positive predictive value of 97.8% (97.8%) and negative predictive value of 84.3% (87.0%). There was no statistically significant difference between the stains. Histopathologic analysis had an overall accuracy of 97.7%, with a sensitivity of 97.2%, specificity and positive predictive value of 100% and a negative predictive value of 88.2%. Conclusion Imprint cytology of CNBs is a sensitive method of detecting malignancies in breast tumors. Diff-Quik is a rapid and reliable approach that can reduce the number of biopsies. Inadequate and suspicious cases should be evaluated based on complementary diagnostic procedures for breast lesions.

Observers of the modern business environment have emphasized that if management accounting is to remain relevant to the realities of the 1990s and beyond, it has to evolve beyond the traditional “gathering, assimilating and reporting function” to encompass the processes whereby information reaches managers. The objective of this teaching case is to assist extending management accounting coverage towards this process. In both Australia and Taiwan, we have successfully used this case to supplement text and end-of-chapter materials at both the advanced undergraduate and graduate levels. The similarity of our teaching experiences between Australia and Taiwan, in conjunction with the generic nature of the case, suggest that it can be used in other national contexts with little or no modification.

Objective: Because estrogens are important in the pathogenesis of both breast cancer and osteoporosis, it has been suggested that the risk of osteoporosis and breast cancer are inversely related. The aim of our study was to evaluate bone mineral density in patients with breast cancer. Methods: Speed of sound, broadband ultrasound attenuation, and the stiffness index of the calcaneus were measured in 1004 subjects (mean age 53.9 years) with an Achilles ultrasound bone densitometer. 148 patients had a history of breast cancer and 856 did not. Breast cancer patients were compared with healthy subjects matched for age, weight, body mass index (BMI), parity, and duration of breast feeding and estrogen exposure. Results: Overall, the patients with breast cancer were 4.4 years older and had higher body weight, BMI and parity, longer duration of breast feeding and estrogen exposure, and a significantly higher speed of sound and stiffness index than healthy controls. In the matched-pairs analysis, women with breast cancer had a higher speed of sound and stiffness index than the controls. Conclusion: Women with breast cancer have a lower risk of osteoporosis than controls. Although the biologic mechanisms linking bone mass and the risk of breast cancer are not fully understood, factors other than cumulative estrogen exposure may play a role. Studies on larger populations are needed to evaluate this relationship.

Objectives: To compare a composite ultrasonometry variable, the stiffness index (SI), with its two component variables of speed of sound (SOS) and broadband ultrasound attenuation (BUA), in identifying post-menopausal women with low bone mineral density (BMD) and/or osteoporotic fracture. Methods: A cross sectional sample of 1217 women (mean (S.D.) age 53.9 (9.7) years) was studied. Risk factors for osteoporosis were assessed by detailed questionnaire and women with diseases, or those taking treatments known to affect bone metabolism were excluded. Women were allocated to one of four groups: pre-menopausal women (n=476), healthy post-menopausal women (n=583), post-menopausal women with low BMD (n=101), and post-menopausal women with osteoporotic fracture (n=57). An Achilles ultrasonometer was used to perform quantitative ultrasonometry (QUS) at the os calcis. The SI, calculated mathematically from SOS and BUA, was computed. Results: Analysis of receiver operating curves (ROC) between healthy post-menopausal women and post-menopausal women with low BMD but no fracture, showed that the area under the curve (AUC) for SI was significantly greater than that for BUA (P

Pituitary adenylate cyclase-activating polypeptide (PACAP) releases LH and FSH from anterior pituitary cells. Although this effect is relatively weak, it has a strong sensitizing action on GnRH-induced gonadotropin secretion. Here we investigated the possibility that ovarian steroids, which are well-known modulators of LH secretion, interact with PACAP and GnRH in pituitary gonadotrophs. Rat pituitary cells were treated for 48 h with vehicle, 1 nmol/l estradiol, 1 nmol/l estradiol + 100 nmol/l progesterone or 48 h with 1 nmol/l estradiol and 4 h with 100 nmol/l progesterone. The cells were stimulated for 3 h with 1 nmol/l GnRH or 100 nmol/l PACAP. Estradiol treatment alone enhanced basal as well as GnRH- or PACAP-stimulated LH secretion. LH release was facilitated by additional short-term progesterone treatment. Long-term treatment with estradiol and progesterone led to reduced LH responses to GnRH and PACAP. Neither treatment paradigms affected cAMP production. However, estradiol treatment led to enhanced cAMP accumulation in quiescent or GnRH-stimulated cells. PACAP-induced increases of cAMP production were inhibited by estradiol treatment. After 7-h preincubation with 10 nmol/l PACAP, cells responded with enhanced LH secretion to GnRH stimulation. When steroid pretreatment was performed the responsiveness of gonadotrophs to low concentrations of GnRH was still increased. In contrast, at high concentrations of GnRH the sensitizing action of PACAP on agonist-induced LH secretion was lost in steroid-treated cells. There were no significant differences between the steroid treatment paradigms. It is concluded that estradiol but not progesterone acts as a modulator of adenylyl cyclase in gonadotrophs. The stimulatory effect of estradiol is thought to be involved in its sensitizing action on agonist-induced LH secretion. The inhibitory effect of estradiol on PACAP-stimulated adenylyl cyclase activities seems to be responsible for the loss of its action to sensitize LH secretory responses to GnRH.

Purpose: This cross-sectional study collected data on the effectiveness, validity and reliability of QUS. Method and Material: Speed of sound (SOS), broadband ultrasound attenuation (BUA) and stiffness index (SI) of the calcaneus were measured in n = 764 postmenopausal patients, mean age 61 years, using the Achilles ultrasound bone densitometer (Lunar Corp., Madison, WI). In addition we measured blood levels of E2 and FSH in 157 patients and correlated these variables with data gathered by a detailed questionnaire. Women using any medication known to effect bone metabolism were excluded from the study. Results: The Achilles shortterm precision in vivo expressed as coefficient of variance was 1.2 % for BUA and 0.17% for SOS and 1.3% for stiffness respectively. A total of 102 women were measured at the right and left calcaneus with a coefficient of correlation of r= 0.92 for SOS, r = 0.84 for BUA and r = 0.93 for SI. Cross-sectional analysis showed a significant yearly postmenopausal decrease of 0.06% for SOS, 0.44% for BUA and 0.74% for SI. Women with a history of osteoporosis (165 patients) as well as 141 women with an osteoporosis-related fracture showed significantly lower results in all ultrasound parameters (SOS, BUA, SI). In conclusion, quantitative ultrasound osteodensitometry of the calcaneus measures properties of bone which continue to decline with age. The low precision error and the high correlation of right vs. left underlines the high technical standard. Conclusion: Our results indicate that QUS is capable of identifying in a precise manner women with previous osteoporotic fractures as well as women with a history of osteoporosis. Hence, QUS may provide a radiation-free, low-cost, easy to handle, fast and mobile method which for the first time could make a screening programme a feasible proposition.

Die hormonelle Substitutionstherapie bringt neben der Behandlung klimakterischer Beschwerden auch einen Benefit fur kardiovaskulare Erkrankungen und Osteoporose. Es existieren aber auch potentielle Risiken. Diese betreffen insbesondere aus Patientinnensicht die Entwicklung von Malignomen. Hier werden die Risiken bezuglich der Entwicklung von Mamma- und Genitalkarzinomen diskutiert. Zusatzlich wird auf die Moglichkeit einer hormonellen Substitutionstherapie nach Behandlung eines Mamma- oder Genitalkarzinomes eingegangen. Zervixkarzinom: Keine Risiken, keine Kontraindikation. Ovarialkarzinom: Ein protektiver Effekt bei der Langzeiteinnahme hormoneller Kontrazeptiva ist gesichert. Fur die Substitutionstherapie konnte das jedoch nicht bestatigt werden. Andererseits erscheint das Risiko einer Malignomentstehung aber auch nicht anzusteigen. Eine Kontraindikation nach Behandlung besteht nicht. Endometriumkarzinom: Hochdosiert und alleinige Ostrogengaben fuhren dosis- und zeitabhangig zu einem 2– bis 20–fach hoherem Risiko an einem Malignom des Endometriums zu erkranken. Durch mindestens 10–tagige zusatzliche Gestagengaben last sich diese Ostrogenwirkung aufheben. Die kombinierte Substitutionstherapie fuhrt sogar zur Minderung des Endometriumkarzinomrisikos im Vergleich zu unbehandelten Frauen. Das behandelte Endometriumkarzinom wird nicht mehr als uneingeschrankte Kontraindikation angesehen. Mammakarzinom: Die Diskussion um eine potentielle Erhohung des Erkrankungsrisikos wird seit vielen Jahren kontrovers gefuhrt. Nach dem derzeitigen Kenntnisstand ist eine hormonelle Substitutions- therapie mit einer Dauer von bis zu 5 Jahren nicht mit einer Erhohung des Mammakarzinomrisikos verbunden. Ein geringer Anstieg last sich dagegen bei Langzeittherapie (> 10 Jahre) nicht ausschliesen. Bestimmte Risikogruppen existieren nach derzeitigem Kenntnisstand nicht. Das behandelte Mammakarzinom gilt als klassische Kontraindikation gegen den Einsatz einer hormonellen Substitutionstherapie. Dies wird heute von vielen als nicht mehr haltbar angesehen. Andererseits liegen keine Daten groseren Umfangs vor, die die Sicherheit einer hormonellen Substitutionstherapie nach Mammakarzinom belegen.

The ovarian steroids estradiol and progesterone act as important modulators of GnRH-induced luteinizing hormone (LH) secretion from anterior pituitary cells. Recently, we demonstrated that the steroids are able to influence GnRH-stimulated Ca2+ mobilization from extra- and intracellular sources. Here we investigated the actions of estradiol and progesterone on GnRH-induced biphasic LH secretory responses in the model of perifused female rat pituitary cells. A 20 min GnRH stimulus elicited biphasic LH responses composed of an initial peak followed by a prolonged plateau phase. Both phases were equally enhanced by long-term (48 h) estradiol treatment. This action was facilitated by subsequent short-term progesterone treatment. In contrast, combined treatment with estradiol and progesterone for 48 h led to inhibited LH secretory profiles. To determine the steroid actions on the extracellular Ca2+ independent component of LH secretion we performed experiments using cells that were perifused with Ca2+ deficient medium. Under these conditions the cells responded exclusively with a single peak phase of LH secretion, which was augmented or inhibited by estradiol and progesterone treatment as described above. To test the hypothesis that an effect of estradiol and progesterone on GnRH-induced polyphophoinositide hydrolysis is responsible for their modulatory actions on Ca2+ signals and LH secretion we measured inositol phosphate (IP) accumulation after different steroid treatment paradigms in rat pituitary cells and alpha T3-1 immortalized gonadotrophs. GnRH-induced IP production was enhanced by long-term estradiol treatment. Short-term exposure of estradiol-primed cells to progesterone did not lead to significant changes of IP production. The long-term progesterone treatment paradigm enhanced GnRH-induced IP formation, while it decreased Ca2+ signals and LH secretion. Alpha T3-1 cells were used to perform more detailed analysis of IP formation. The actions of estradiol and progesterone on the production of inositol mono-, bis-, and trisphosphates were similar to those observed in the mixed cell population. It is concluded that estradiol and progesterone modulate both peak and plateau phases of GnRH-stimulated LH secretory responses, effects which are associated with their impact on Ca2+ signals. Our findings argue against a role of IP modulation in the mechanism of progesterone actions on Ca2+ signaling and LH secretion in gonadotrophs. Such a mechanism might be involved in the positive effects of estradiol in these cells.

In estradiol-treated pituitary cells, progesterone enhances gonadotropin-releasing hormone (GnRH)-induced LH secretion from cultured rat pituitary cells during short-term treatment but attenuates this response during prolonged treatment. In the present study, the effects of gonadal steroids on GnRH-induced cytoplasmic calcium ([Ca2+]i) responses in gonadotrophs were analyzed in rat pituitary cells and immortalized (alpha T3-1) murine gonadotrophs. Ca2+ responses were measured in cell suspensions and single gonadotrophs, loaded with Fura-2 or Indo-1, respectively, and pretreated for 48 h with 1 nM estradiol with or without 100 nM progesterone, or for 48 h with 1 nM estradiol and then for 3 h with 100 nM progesterone. In cells of the alpha T3-1 gonadotroph lineage, GnRH elicited biphasic Ca2+ signals composed of an initial peak response followed by a prolonged plateau phase. The amplitudes of both the extracellular Ca(2+)-independent spike phase and the extracellular Ca(2+)-dependent plateau phase were enhanced or inhibited by short- or long-term progesterone treatment, respectively. In single pituitary gonadotrophs, GnRH (0.5 nM) elicited oscillatory responses due to intermittent release and uptake of Ca2+ from intracellular stores. Treatment with progesterone shifted the oscillatory signal toward biphasic (3 h) or subthreshold (48 h) response profiles, revealing a steroid-induced change in the pattern of Ca2+ mobilization. In addition to these agonist-induced responses, the transient [Ca2+]i responses of pituitary cells and individual gonadotrophs to high K+ were enhanced or inhibited after short- or long-term progesterone treatment, respectively. These actions were correlated with the effects of progesterone on K(+)-induced LH secretion. The [Ca2+]i and LH secretory responses to phorbol ester treatment were also enhanced by short-term exposure of the cells to progesterone. The results demonstrate that the stimulatory and inhibitory effects of progesterone on agonist-induced Ca2+ signaling result from changes in Ca2+ mobilization and entry, and contribute to the modulatory actions of the steroid on GnRH-induced LH secretion.

This study was designed to elucidate the signal transduction mechanisms, mediating the antiproliferative effects of analogs of luteinizing hormone releasing hormone (LHRH) on cell lines derived from human cancers of the ovary (EFO-21, EFO-27) and the endometrium (HEC-1A, Ishikawa). The LHRH agonist triptorelin had no measurable effects on the activity of phospholipase C, protein kinase C, or adenylate cyclase in all 4 cell lines, though these enzymes could be activated through pharmacological stimuli. The proliferation of EFO-21, EFO-27 and HEC-1A cells in serum/phenol red-free medium was significantly stimulated by epidermal growth factor (EGF). This mitogenic effect of EGF was dose dependently antagonized by triptorelin, without affecting the concentrations of EGF receptors. Net tyrosine phosphorylation induced by 1 nM EGF was nearly completely suppressed by simultaneous addition of 10 mu M triptorelin or preincubation for 48 h with 100 nM triptorelin. This inhibitory effect of the LHRH agonist on EGF-induced net tyrosine phosphorylation was partly antagonized by exposure to 100 mu M sodium vandate, an inhibitor of phosphotyrosine phosphatase. In EFO-21, EFO-27, and HEC-1A cells exposure to 100 nM EGF for 5 min induced an approximately 5-fold increase in activity of mitogen activated protein kinase (MAP-kinase)/extracellular signal regulated kinase (ERK) which was virtually nullified, when the cells were exposed for 15 min to 10 mu M triptorelin. These data suggest that LHRH signal transduction mechanisms based on the activation of phospholipase C, protein kinase C, and adenylate cyclase, which operate in the pituitary gonadotroph, are not necessarily involved in the mediation of the antiproliferative effects of triptorelin in these ovarian and endometrial cancer cell lines. Instead our findings support the hypothesis that triptorelin interferes with mitogenic signal transduction, probably through antagonizing tyrosine kinase activity of the EGF receptor.

Although specific binding sites for LH-releasing hormone (LHRH) and its analogs have been demonstrated in biopsy samples of human endometrial cancer, their biological significance remains obscure. In this study we evaluated whether binding sites for LHRH are also present in the human endometrial cancer cell lines HEC-1A and Ishikawa and if such sites could mediate antiproliferative effects of LHRH analogs. Using [125I,D-Trp6]LHRH as a ligand, a high affinity/low capacity binding site was detected in both lines: HEC-1A line, dissociation constant (Kd)1 = 5.7 x 10(-9) mol/L, binding capacity (Bmax)1 = 78 fmol/10(6) cells; Ishikawa line, Kd1 = 4.2 x 10(-9) mol/L, Bmax1 = 29 fmol/10(6) cells. In addition, a second class of low affinity/high capacity binding sites for LHRH was demonstrated (HEC-1A line, Kd2 = 1.4 x 10(-6) mol/L, Bmax2 = 21 pmol/10(6) cells; Ishikawa, Kd2 = 4 x 10(-6) mol/L, Bmax2 = 32 pmol/10(6) cells). In the presence of 10(-5) mol/L agonist [D-Trp6]LHRH (triptorelin), the proliferation of HEC-1A and Ishikawa cell lines was significantly reduced to 76 +/- 2% and 88 +/- 4% of controls, respectively, after 24 h and to 64 +/- 2% and 62 +/- 2%, respectively, after 6 days. Dose-response experiments showed that lower concentrations (10(-9) mol/L) of the agonist decreased the proliferation to 80 +/- 1% for the HEC-1A line and 71 +/- 2% of controls for the Ishikawa line after 6 days. Antiproliferative effects are enhanced by increasing the doses of triptorelin and were maximal in this series of experiments at 10(-5) mol/L, the proliferation in the HEC-1A line being 62 +/- 1% and in the Ishikawa line 52 +/- 2% of controls, respectively. Similar time- and dose-dependent antiproliferative effects were obtained in both cell lines with the LHRH antagonist SB-75 (cetrorelix). These data suggest that LHRH analogs can directly inhibit the proliferation of human endometrial cancer cells in vitro. This direct action could be mediated through the high affinity LHRH binding sites.

This study demonstrates for the first time, that medroxyprogesterone acetate (MPA) inhibits the proliferation of the estrogen and progesterone receptor negative mammary cancer cell line MFM-223 via the androgen receptor. MPA is a progestin, which is used in the hormonal treatment of disseminated breast cancer. It binds to the progesterone, androgen, and glucocorticoid receptor and may exert its antiproliferative effects via different receptors. MFM-223 human mammary cancer cells contain a very high level of androgen receptors (160 fmol/mg protein) and low levels of estrogen, progesterone, and glucocorticoid receptors (20 fmol/mg protein). This cell line provides therefore a good model system to analyze the possible role of the androgen receptor in the action of MPA avoiding interference with other steroid hormone receptors. Effective inhibition of proliferation is achieved by 10 nM MPA or 1 nM of the androgen dihydrotestosterone, corresponding well to the binding affinities of both compounds (3.6 and 0.18 nM, respectively). The involvement of the androgen receptor was confirmed by competition experiments with antiandrogens. Furthermore, MFM-DHT cells, which are an androgen resistant subline of MFM-223 cells, are also resistant to MPA. This data supports the involvement of the androgen receptor in the action of MPA and additionally rules out direct hormone-independent cytotoxic effects of MPA.

During the last two decades, considerable experimental evidence has been collected indicating that epithelial ovarian cancer might be gonadotropin dependent. LH and FSH receptors have been described in some of these tumors. The proliferation of ovarian cancer cells could be stimulated in vitro by gonadotropins. Suppression of endogenous LH and FSH secretion by GnRH-agonist treatment inhibited the growth of experimental or heterotransplanted ovarian cancers in various animal models. A number of recent phase II clinical trials have shown that the application of GnRH-agonists can lead to remission or stable disease in patients with relapsed advanced ovarian cancer. At present, prospective controlled clinical studies are being performed to assess the efficacy of GnRH-agonist treatment in addition to conventional surgical and cytostatic therapy in ovarian cancer in FIGO stages III and IV. Also, direct effects of GnRH analogues on ovarian cancer seem possible: a GnRH-like protein has been found in the human ovary. Our group discovered and partially characterized a specific GnRH-binding site (mol. wt 63.2 kDa) in ovarian cancer which is very similar to other human extrapituitary GnRH-binding sites of the low affinity, high capacity type, e.g. in breast cancer or the placenta. Recently, other groups have described also high affinity GnRH-agonist binding sites in ovarian cancer as well as in other extrapituitary tissues. First results from our laboratory indicate that the proliferation of certain ovarian cancer cell lines in vitro is reduced by both agonistic and antagonistic analogues of GnRH. Other authors were able to inhibit gonadotropin-induced in vitro proliferation of ovarian cancer cell lines by co-incubation with a GnRH-agonist.(ABSTRACT TRUNCATED AT 250 WORDS)

Haufigkeit und Mortalitat machen die Brustkrebserkrankung zu einem herausragenden onkologischen Versorgungsproblem im deutschen Gesundheitswesen. Die arztlichen Anforderungen auf diesem Sektor weisen eine derartige Komplexitat auf, dass Diagnose und Therapie von Mammakarzinomen nicht mehr durch eine Fachdisziplin allein geleistet werden konnen. Vielmehr bedarf es eines flachendeckenden, qualitatsgesicherten, fach- und sektorubergreifenden Versorgungsnetzes, das neben den krankheitsbedingten Organveranderungen das gesamte soziale Umfeld einbezieht. Letztlich betrifft dies alle Lebensbereiche der Frau, wie psychisches und physisches Wohlbefinden, Partnerschaft und Familienplanung, Beruf und Freizeit, manchmal auch die finanzielle Lebensgrundlage.

In this study, we examine two factors that impact managers' willingness to share private information during the project review stage of capital budgeting. Drawing on the cognitive dissonance theory and the agency theory, we find that both high perceived personal responsibility and the use of project reviews for performance evaluation result in a greater tendency for managers to withhold negative private information. However, we do not find an interaction between these two factors. Our study makes a contribution to both the academic literature investigating factors affecting project reviews and the practitioner literature looking at design and implementation of effective project reviews. © 2009 AFAANZ.