[From the concept of guilt to the value-free notification of errors in medicine. Risks, errors and patient safety]. / Von der Schuldfrage zur Fehlerkultur in der Medizin. Risiken, Fehler und Patientensicherheit.

The number of liability cases but also the size of individual claims due to alleged treatment errors are increasing steadily. Spectacular sentences, especially in the USA, encourage this trend. Wherever human beings work, errors happen. The health care system is particularly susceptible and shows a high potential for errors. Therefore risk management has to be given top priority in hospitals. Preparing the introduction of critical incident reporting (CIR) as the means to notify errors is time-consuming and calls for a change in attitude because in many places the necessary base of trust has to be created first. CIR is not made to find the guilty and punish them but to uncover the origins of errors in order to eliminate them. The Department of Anesthesiology of the University Hospital of Basel has developed an electronic error notification system, which, in collaboration with the Swiss Medical Association, allows each specialist society to participate electronically in a CIR system (CIRS) in order to create the largest database possible and thereby to allow statements concerning the extent and type of error sources in medicine. After a pilot project in 2000-2004, the Swiss Society of Gynecology and Obstetrics is now progressively introducing the 'CIRS Medical' of the Swiss Medical Association. In our country, such programs are vulnerable to judicial intervention due to the lack of explicit legal guarantees of protection. High-quality data registration and skillful counseling are all the more important. Hospital directors and managers are called upon to examine those incidents which are based on errors inherent in the system.

[Morbidity of dilatation and evacuation in the second trimester: an analysis]. / Morbiditat einzeitiger Abortausraumungen im 2. Trimenon: Eine Standortbestimmung.

OBJECTIVE: To compare the rates of complications of dilatation and evacuation (D&E) in the second trimester of pregnancy. STUDY DESIGN: Retrospective analysis of early complications after D&E in the second trimester (group A: 1988-1994) in comparison with D&E in the first trimester (group B: 1997) and with the induction of abortion by extra-amniotic application of prostaglandins in the second trimester of pregnancy (literature). RESULTS: The overall complication rate of D&E was statistically significantly higher in the second than in the first trimester (p < 0.0001). The most frequent complication in both groups was a blood loss > 500 ml (p < 0.009). As with blood loss, there was a statistically significant increase in the incidence of postoperative bleeding (p < 0.001) and fever > 38 degrees C (p = 0.042) with rising gestational age, too. We registered similar rates for incomplete abortion, infection, cervical injury, uterine perforation and thrombosis. CONCLUSION: Second-trimester pregnancy termination with D&E is associated with higher morbidity rates than in the first trimester. Overall, the rates of complications of D&E in our study were acceptable and comparable with the results of previous studies. Compared with the induction of abortion by extra-amniotic prostaglandins, D&E shows lower morbidity rates. In particular, the advantages of D&E are in the early second trimester.

[Contraception and proception--competence of the gynaecologist in the planning of a woman's life]. / Kontra- und Prozeption--Zur Kompetenz des Frauenarztes/der Frauenärztin bei der Lebensplanung der Frau.

Contra- and proception provoke different answers in our country and culture than globally speaking, particularly regarding non-industrialized nations. Contraception should be viewed as a means of preventive medicine, especially as a means of avoiding the psychosocial emergency of an unwanted pregnancy and potentially subsequent pregnancy termination. In this light, contraceptive counselling to teenagers is of particular importance. Reliable contraception does not cause a change of morals but supports and facilitates lifestyle and provides security. This aspect interacts closely with social and family politics. The integration of contraception into a woman's concept of life is decidedly dependent on these circumstances. The gynaecologist is a participant in the development of this concept, particularly for women who initially practice contraception, often in pursuit of a professional career, and later--often too late or perhaps never--bear an only child with maximal intention or potentially even after assisted reproductive medical intervention. The initially desired infertility frequently turns into the unfulfilled desire to bear children. The issues at hand are innovative social and sexual pedagogics that eliminate the separation between career and family. In the awareness of this pedagogic task, gynaecologists participate in the design of a woman's life concept as well as in the demographic change of society.

[Must the postgraduate medical training for specialists of gynecology and obstetrics be reconsidered?]. / Muss die Weiterbildung zum Facharzt Gynäkologie und Geburtshilfe in der Schweiz überdacht werden?

Our specialty is based on a 3-pillared concept. The professional political development again requires a discussion on the separation of 'nonoperating' and 'operating' specialists. In addition, the future model of the 'gynecologist as family doctor for women' becomes an interesting topic. The guidelines for the proceedings in the case of suspect and positive cytological smears of the cervix have been revised with regard to the Bethesda nomenclature and will be published this year.

Detailed anatomy of the abdomen and pelvis of the visible human female.

We report on a virtual anatomical preparation of the abdomen and pelvis of the Visible Human Female (VHF) for laparoscopic surgery training. The detailed cross-sectional image data set from the U.S. National Library of Medicine was used as the basis to build an exemplary model of the female abdomen and pelvis. Segmentation software was developed to delineate organ outlines and more than 300 structures of interest, including organs, blood vessels, bones, muscles, and ligaments, have been segmented and three-dimensionally reconstructed. Analyzing the normal anatomy we found several variations and pathologies of the VHF, such as missing muscles (gemellus superior, psoas minor), additional veins as well as spondylophytes (vertebral column, pubic bone), and colon diverticula. The complete data set may be viewed on the home page of the project (http://www.vision.ee.ethz.ch/projects/Lasso/start.html).

Effect of rofecoxib on platelet aggregation and blood loss in gynaecological and breast surgery compared with diclofenac.

BACKGROUND: Non-selective cyclooxygenase (COX) inhibitors or non-steroidal anti- inflammatory drugs (NSAIDs) are frequently omitted for perioperative pain relief because of potential side-effects. COX-2-selective inhibitors may have a more favourable side-effect profile. This study tested the hypothesis that the COX-2-selective inhibitor rofecoxib has less influence on platelet function than the NSAID diclofenac in gynaecological surgery. In addition, analgesic efficacy and side-effects of the two drugs were compared. METHODS: In this single-centre, prospective, double-blind, active controlled study, women undergoing vaginal hysterectomy (n=25) or breast surgery (n=25) under general anaesthesia received preoperatively 50 mg of rofecoxib p.o. followed 8 and 16 h later by two doses of placebo or three doses of diclofenac 50 mg p.o. at the same time points. We assessed arachidonic acid-stimulated platelet aggregation before and 4 h after the first dose of study medication, estimated intraoperative blood loss, and haemoglobin loss until the first morning after surgery. Analgesic efficacy, use of rescue analgesics, and side-effects were also recorded. RESULTS: In the rofecoxib group, stimulated platelet aggregation was disturbed less (P=0.02), and estimated intraoperative blood loss (P=0.01) and the decrease in haemoglobin were lower (P=0.01). At similar pain ratings, the use of anti-emetic drugs was less in the rofecoxib group (P=0.03). CONCLUSION: Besides having a smaller effect on platelet aggregation, one oral dose of rofecoxib 50 mg given before surgery provided postoperative analgesia similar to that given by three doses of diclofenac 50 mg and was associated with less use of anti-emetics and less surgical blood loss in gynaecological surgery compared with diclofenac.

[Preterm labour and risk factors]. / Frühgeburt und Risikofaktoren.

Infections, stress and haemorrhages are risk factors in the pathophysiology of preterm delivery. Genital infections can be diagnosed and treated, and thus the frequency of preterm labour is lowered. How psychosocial burdens which are also stress factors can be influenced remains uncertain.

[New developments in hormone replacement therapy]. / Neue Erkenntnisse in der Hormonersatztherapie.

Hormone replacement therapy with estrogen and progesterone does not appear to protect against Alzheimer's disease and does not improve cognitive functioning. Long-term administration of estrogen as monotherapy may be associated with an increased risk of ovarian cancer.

Brostallicin (PNU-166196)--a new DNA minor groove binder that retains sensitivity in DNA mismatch repair-deficient tumour cells.

Defects in DNA mismatch repair (MMR) are associated with a predisposition to tumorigenesis and with drug resistance owing to high mutation rates and failure to engage DNA-damage-induced apoptosis. DNA minor groove binders (MGBs) are a class of anticancer agents highly effective in a variety of human cancers. Owing to their mode of action, DNA MGB-induced DNA damage may be a substrate for DNA MMR. This study was aimed at investigating the effect of loss of MMR on the sensitivity to brostallicin (PNU-166196), a novel synthetic alpha-bromoacrylic, second-generation DNA MGB currently in Phase II clinical trials and structurally related to distamycin A. Brostallicin activity was compared to a benzoyl mustard derivative of distamycin A (tallimustine). We report that the sensitivities of MLH1-deficient and -proficient HCT116 human colon carcinoma cells were comparable after treatment with brostallicin, while tallimustine resulted in a three times lower cytotoxicity in MLH1-deficient than in -proficient cells. MSH2-deficient HEC59 parental endometrial adenocarcinoma cells were as sensitive as the proficient HEC59+ch2 cells after brostallicin treatment, but were 1.8-fold resistant after tallimustine treatment as compared to the MSH2-proficient HEC59+ch2 counterpart. In addition, p53-deficient mouse fibroblasts lacking PMS2 were as sensitive to brostallicin as PMS2-proficient cells, but were 1.6-fold resistant to tallimustine. Loss of neither ATM nor DNA-PK affected sensitivity to brostallicin in p53-deficient mouse embryonic fibroblasts, indicating that brostallicin-induced cytotoxicity in a p53-deficient genetic background does not seem to require these kinases. These data show that, unlike other DNA MGBs, MMR-deficient cells retain their sensitivity to this new alpha-bromoacrylic derivative, indicating that brostallicin-induced cytotoxicity does not depend on functional DNA MMR. Since DNA MMR deficiency is common in numerous types of tumours, brostallicin potentially offers the advantage of being effective against MMR-defective tumours that are refractory to several anticancer agents.

[The Gynecologic and Obstetric Review (Gynaekologisch-geburtshilfliche Rundschau) faces a new challenge!]. / Die "Gynäkologisch-geburtshilfliche Rundschau" steht vor einer neuen Herausforderung!

The Austrian Society of Gynecology and Obstetrics gave notice of organ membership and at the same time of the compulsory subscription to the Gynecologic and Obstetric Review/ Gynäkologisch-geburtshilfliche Rundschau in favor of a journal oriented more towards professional politics. Thus ends a long-standing international tradition. This also means a new challenge for the Gynecologic and Obstetric Review/Gynäkologisch-geburtshilfliche Rundschau.

Loss of atm sensitises p53-deficient cells to topoisomerase poisons and antimetabolites.

BACKGROUND: Ataxia-telangiectasia is a pleiotropic autosomal recessive disorder caused by mutations in the ATM gene. In addition to a profound cancer predisposition, another hallmark of ataxia-telangiectasia is radiosensitivity. Recently, p53-null mouse fibroblasts have been reported to be radiosensitised by the concurrent loss of ATM. MATERIALS AND METHODS: We compared the sensitivity of atm(+/+)/p53(-/-) and atm(-/-)/p53(-/-) mouse embryonic fibroblasts to different classes of chemotherapeutic agents using the MTT assay, Trypan Blue exclusion and fluorescence-activated cell sorting for cell cycle and apoptosis analyses. RESULTS: Loss of ATM function in p53-deficient cells resulted in a 2- to 4-fold increase in sensitivity to the topoisomerase I poisons camptothecin and topotecan, to the topoisomerase II poisons doxorubicin, epirubicin and etoposide, and to the antimetabolites 5-fluorouracil and gemcitabine, but not to the platinum compounds cisplatin, carboplatin and oxaliplatin, the taxanes docetaxel and paclitaxel, or to busulfan. Loss of ATM function did not result in increased apoptosis, but resulted in increased Trypan Blue staining in response to epirubicin, suggesting that processes other than apoptosis may mediate cytotoxicity. ATM deficiency did not alter the extent of G(1)/S or G(2)/M cell cycle phase accumulation produced by epirubicin, suggesting that enhanced sensitivity was not due to failure of checkpoint activation. CONCLUSIONS: We provide further evidence that ATM is involved in regulating cellular defences against some cytotoxic agents in the absence of p53. Tumour-targeted functional inhibition of ATM may be a valuable strategy for increasing the efficacy of anticancer agents in the treatment of p53-mutant cancers.

[Anti-aging or better aging: a contribution to the prevention of aging?]. / Anti-Aging oder "Better Aging"--Ein Beitrag zur Alterungsprävention?

Anti-aging wants to influence the quality of the second half of life so that chronic damage to health can also be prevented at a higher age with a good quality of life. Thus, molecular biological tests should become the basis for an individualized, preventive hormone therapy. In this context, the question arises whether for each woman in the menopause a risk profile of disturbances of hormone metabolism can already be recognized in her pattern of polymorphisms, although scientific evidence has been lacking until now. Even the topic of the adrenopause, which--among other features--is characterized by an age-specific, partial adrenal insufficiency, must not be neglected in the context of the problem of anti-aging.

[Is continuing medical education under suspicion of corruption? Contribution to the discussion by the Committee for Quality Preservation of the Swiss Society of Gynaecology and Obstetrics]. / Arztliche Fortbildung unter Korruptionsverdacht?. Diskussionsbeitrag der Kommission Qualitätssicherung der Schweizerischen Gesellschaft für Gynäkologie und Geburtshilfe.

The requirements laid down by law and by the medical profession itself with regard to continuing medical education have recently been tightened. The cost of good training is high, both in time and money. Sponsoring, especially by the pharmaceutical industry, has helped to keep costs down for individual participants. The question of a tariff system for the payment of compulsory training is now being raised. Rates have been set to ensure that, in the future, indirect costs are covered. In the event of a full tariff-based payment of costs being introduced, various disadvantages could be expected both for participants and the quality of the training. Changes in Swiss criminal law and the new medicines act do not forbid sponsoring, but they do call for rules of professional ethics and of personnel law in public hospitals governing behaviour in respect of funding by sponsors. Various sponsoring models are conceivable with differences in allocation to organizers, individual participants or distribution via a pool system. There are strong arguments in favour of continuing the existing practice of mixed funding by participants and sponsoring, provided that it is subject to certain rules of transparency. What is lacking to date is a political decision on the issue of funding for continuing medical education.

[Science and law in assisted reproductive medicine -- two sides of the same token]. / Wissenschaft und Recht der Reproduktionsmedizin -- zwei Seiten einer Medaille.

The topic of assisted reproductive medicine (ART) illustrates the two-sidedness of all medical advances. It encompasses not only a responsibility for research, but also a responsibility to research. Current discussion revolves around the central question whether an all too strict interpretation of the German 'Embryonenschutzgesetz' (law to protect the embryo) with the resulting medical guidelines hinders the establishment of an ART practice corresponding to international standards. Current discussion, particularly in view of a new ART legislature in process, leaves the following topics open to debate: heterologous oocyte and sperm donations and a possible 'split' parenthood, the marital status of prospective couples and the serious clinical problem of multiple-gestation pregnancies. The technically feasible frequently surpasses what can or should ethically and legally be made possible.

Increased sensitivity of p53-deficient cells to anticancer agents due to loss of Pms2.

A large fraction of human tumours carries mutations in the p53 gene. p53 plays a central role in controlling cell cycle checkpoint regulation, DNA repair, transcription, and apoptosis upon genotoxic stress. Lack of p53 function impairs these cellular processes, and this may be the basis of resistance to chemotherapeutic regimens. By virtue of the involvement of DNA mismatch repair in modulating cytotoxic pathways in response to DNA damaging agents, we investigated the effects of loss of Pms2 on the sensitivity to a panel of widely used anticancer agents in E1A/Ha-Ras-transformed p53-null mouse fibroblasts either proficient or deficient in Pms2. We report that lack of the Pms2 gene is associated with an increased sensitivity, ranging from 2-6-fold, to some types of anticancer agents including the topoisomerase II poisons doxorubicin, etoposide and mitoxantrone, the platinum compounds cisplatin and oxaliplatin, the taxanes docetaxel and paclitaxel, and the antimetabolite gemcitabine. In contrast, no change in sensitivity was found after treatment with 5-fluorouracil. Cell cycle analysis revealed that both, Pms2-deficient and -proficient cells, retain the ability to arrest at the G2/M upon cisplatin treatment. The data indicate that the concomitant loss of Pms2 function chemosensitises p53-deficient cells to some types of anticancer agents, that Pms2 positively modulates cell survival by mechanisms independent of p53, and that increased cytotoxicity is paralleled by increased apoptosis. Tumour-targeted functional inhibition of Pms2 may be a valuable strategy for increasing the efficacy of anticancer agents in the treatment of p53-mutant cancers.

[Breast diagnosis: new acquisitions and developments]. / Mammadiagnostik: Neue Erkenntnisse und Entwicklungen.

The development and refinement of breast diagnosis have increased the significance of breast ultrasound, have led to the establishment of mammographic classification criteria (BI-RADS) and to the standardisation of the terminology used for reporting the results and thus its codification. Targeted stereotactic biopsies (Mammotome and SiteSelect) have become established methods of pretreatment diagnosis.

[Stereotaxic breast biopsy techniques have become the standard of care for mammographically suspicious lesions]. / Stellenwert der modernen stereotaktischen Biopsiemethoden bei mammographisch suspekten Läsionen.

An optimal technique for the evaluation of nonpalpable, suspicious mammographic lesions should have a low technical failure rate, no false-negative results and should remove the lesion completely. Since most of these lesions are benign, the procedure should be carried out in an outpatient setting without general anesthesia. Cancer is missed in 2.6% of cases with excisional biopsy following needle localization. Furthermore, 50-83% of these patients undergo a second surgical intervention for definitive surgical treatment. In contrast, the rate of missed cancers is less than 0.7% following stereotaxic core or large-core biopsies. However, using these techniques, discordant results and histologic high-risk lesions need to be recognized and reexcized. The cost-effectiveness of stereotaxic vacuum-assisted core biopsy has been demonstrated. Stereotaxic breast biopsy techniques such as vacuum-assisted core biopsy and large-core biopsy for suspicious mammographic lesions have low false-negative rates and result in few histologic underestimations.