Adapting a commercial shear rheometer for applications in cartilage research.

Cartilage research typically requires a broad range of experimental characterization techniques and thus various testing setups. Here, we describe how several of those tests can be performed with a single experimental platform, i.e. a commercial shear rheometer. Although primarily designed for shear experiments, such a rheometer can be equipped with different adapters to perform indentation and creep measurements, quantify alterations in the sample thickness, and conduct friction measurements in addition to shear rheology. Beyond combining four distinct experimental methods into one setup, the modified rheometer allows for performing material characterizations over a broad range of time scales, frequencies, and normal loads.

[52-year-old patient with painful ascites following fall from a bicycle]. / 52-jähriger Patient mit schmerzhaftem Aszites nach Fahrradsturz.

A 52-year-old patient presented with a ruptured abdominal aortic aneurysm after bicycle trauma. He was treated with a vascular prosthesis. His postoperative recovery was complicated by acute renal failure with anuria for which he was commenced on dialysis. His main persistent symptoms were severe abdominal pain, nausea and vomiting as well as massive ascites. Despite several attempts of a diagnostic and therapeutic ascitic tap, we were initially unable to make a diagnosis. Following each attempted paracentesis, symptoms initially improved. Ascites did reaccumulate, however, and we had to continue with his dialysis. Measurement of creatinine in the ascitic fluid was the key to the correct diagnosis. The ascitic fluid creatinine was nearly 3 times higher than the serum creatinine. The consequent MRI scan of the abdomen with excretion urogram demonstrated a leakage of the left ureter at the junction of the proximal and the middle third of the ureter with contrast leaking into the surrounding fluid.

Should commercial organ donation be legalized in Germany? An ethical discourse.

OBJECTIVE: We evaluated the arguments pro and con concerning kidney sales from a German perspective. At present, we see social, medical, and ethical reasons why organ selling should not be legalized in Germany. DISCUSSION: Legalization of organ selling would weaken the principle of solidarity within the German health system. Conversely, profit making will undermine the principle of social justice. Within the present social system in Germany, there is no economic pressure to sell an organ to save life, and there is no medical need to buy a kidney. Also, there exists the risk that opening the market for organ sales will de-motivate potential directed organ donors. Relatives would have more doubts about giving their consent to donate organs of their deceased. Moreover, the historical experience with the "action T4" of the Nazi regime sensitized German society for the categorical imperative set forth by Immanuel Kant (1724-1804), namely that man is not a means, but an end to himself. By selling one's kidney, the donor uses himself as a means and as an instrument for the end result of gaining money. With directed organ donation, the welfare of the recipient is the end result. The pending reform of the German health system needs a more communitarian sense, which will be eroded should organs be sold and no longer donated as gifts. CONCLUSION: Germany's special historical experience and a deeply embedded consent toward ethical values give reason for the prohibition of organ selling in Germany.

[Drug information services for physicians and patients. Acceptance and benefits]. / Arzneimittelberatungsdienste für Arzte und Patienten. Akzeptanz und Nutzenbewertung.

The growing number of medicinal products and innovations has led to great complexity in the pharmaceutical market. The variety of possible drug interactions and side effects can only be overviewed with difficulty. Therefore, it is necessary that services for physicians be offered in order to provide critically evaluated and independent drug information for pharmacotherapy. In recent decades, a series of hospital based drug information centres have been established. Their quality and usefulness for patients have been positively evaluated by the users. Many patients are also insufficiently informed on their own drug therapy. This deficit is based on a general lack in communication between the patient and physician. Patient-orientated drug information services can help strengthen patients in their drug therapy and self management of symptoms, and to improve compliance. Such services have also been positively evaluated by patients.

Estrogen receptor 1 haplotype does not regulate oral contraceptive-induced changes in haemostasis and inflammation risk factors for venous and arterial thrombosis.

BACKGROUND: Administration of oral contraceptives (OCs) has profound effects on the plasma levels of haemostasis and inflammation variables, resulting in an increased thrombosis risk. Individuals show large differences in the response of these variables to OCs. Polymorphism in the estrogen receptor-1 (ER1) gene may explain part of this inter-individual response. METHODS: We investigated the relationship between variants (c.454-397T>C and c.454-351A>G polymorphisms and the combined haplotype) in the ER1 gene in relation to changes in haemostasis and inflammation variables that are known risk factors for thrombosis in 507 healthy, nonsmoking, nulliparous women receiving six cycles of monophasic OCs with 20, 30 or 50 microg/day estrogen. RESULTS: A significant relationship was observed between the ER1 haplotype and changes in tissue-type plasminogen activator activity (P = 0.006), but no clear interaction pattern between the genotypes or between the estrogen doses was seen. No relationships were observed for the other variables, neither in the haplotype nor in the single polymorphism analysis. CONCLUSION: The ER1 haplotype does not have a strong effect on the estrogen-induced changes in haemostasis and inflammation risk markers for arterial and venous thrombosis.

Effect of four oral contraceptives on hemostatic parameters.

This is the first double-blind, controlled, randomized study comparing the effect of different estrogen components in oral contraceptives (OCs) on hemostasis variables. Four groups of 25 women each were treated for six cycles with monophasic combinations containing 21 tablets with either 30 microg ethinylestradiol (EE) + 2 mg dienogest (DNG) (30EE/DNG), 20 microg EE + 2 mg DNG (20EE/DNG), 10 microg EE + 2 mg estradiol valerate (EV) + 2 mg DNG (EE/EV/DNG) or 20 microg EE + 100 microg levonorgestrel (LNG) (EE/LNG). Blood samples were taken on Days 21-26 of the control cycle and on Days 18-21 of the first, third and sixth treatment cycle. Treatment with all four OCs caused an increase in levels of fibrinogen, prothrombin fragment 1+2, D-dimer, plasminogen, plasmin-antiplasmin complex and an increase in protein C activity, a decrease in antithrombin activity, tissue-plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI), and a slight decrease in the sensitivity to activated protein C, but no significant change in that of the thrombin-antithrombin complex. In users of the DNG-containing OCs, the reduction in total and free protein S, and in t-PA and PAI was dependent on the EE dose, while factor VII activity was elevated, but not significantly different from EE/LNG. The results are in agreement with those of previous studies. The effects of EE/EV/DNG on total and free protein S and on t-PA and PAI were lower than those of 20EE/DNG, suggesting that the impact of 2 mg EV on several hemostasis variables is less than that of 10 microg EE. The results show an antagonistic effect of LNG on the EE-induced rise of factor VII activity and fragment 1+2 and on the EE-dependent reduction of total and free protein S.

Cycle control, quality of life and acne with two low-dose oral contraceptives containing 20 microg ethinylestradiol.

OBJECTIVES: Poor cycle control and tolerability can be reasons for irregular pill intake. This study compared the tolerability of two low-dose oral contraceptives and their effect on cycle control. METHODS: In this open, group-comparative, randomized multicenter trial in Germany and the Netherlands, women received either 20 microg ethinylestradiol plus 150 microg desogestrel (20EE/DSG; n = 500) or 20 microg ethinylestradiol plus 100 microg levonorgestrel (20EE/LNG; n = 498) for six treatment cycles. Cycle control, dysmenorrhea and premenstrual syndrome (PMS) were assessed using diary cards. Tolerability was assessed using the self-administered questionnaires Psychological General Well-Being Index (PGWBI) and the Profile of Mood States (POMS). Acne was assessed by objective (acne counts) and subjective (no, moderate, mild, severe) acne scoring of the facial area at baseline and treatment cycles 1, 3 and 6. RESULTS: A total of 404 (78.1%) and 384 (75.3%) women in the 20EE/DSG and 20EE/LNG groups, respectively, completed the trial. The occurrence rate of irregular bleeding and spotting was statistically significantly higher with 20EE/LNG than with 20EE/DSG (0.18 vs. 0.13; p < 0.05). The mean number of bleeding-spotting days per cycle was statistically significantly higher with 20EE/LNG than with 20EE/DSG (0.63 vs. 0.48; p < 0.05). Early withdrawal bleeding was more frequent with 20EE/LNG (0.15 vs. 0.08; p < 0.005), whereas continued withdrawal bleeding was more frequent with 20EE/DSG (0.32 vs. 0.45; p < 0.001); absence of withdrawal bleeding was comparable (0.06 vs. 0.04, respectively). Thirteen subjects in the 20EE/LNG group and three in the 20EE/DSG group discontinued due to unacceptable bleeding (p < 0.05). Dysmenorrhea and PMS decreased comparably in both groups. There were no differences between groups for the mean total scores of PGWBI or POMS at all time-points. Fewer acne lesions were counted with 20EE/DSG vs. 20EE/LNG after six cycles (p < 0.05). The subjective acne scores supported this finding. CONCLUSIONS: 20EE/DSG provided better cycle control than 20EE/LNG with less treatment discontinuation due to unacceptable bleeding. There were no apparent differences between the two groups regarding tolerability and quality of life. There was less acne with 20EE/DSG.

Effect of four oral contraceptives on thyroid hormones, adrenal and blood pressure parameters.

In a double-blind, controlled, randomized, four-arm, bicentric clinical study, the effect of four oral contraceptives (OCs) on thyroid hormone parameters, cortisol, aldosterone, endothelin-1 and angiotensin II was investigated. Four groups composed of 25 volunteers each (ages between 18 and 35 years) were treated for six cycles with monophasic combinations containing 21 tablets with either 30 microg ethinylestradiol (EE) + 2 mg dienogest (DNG) (30EE/DNG), 20 microg EE + 2 mg DNG (20EE/DNG), 10 microg EE + 2 mg estradiol valerate (EV) + 2 mg DNG (EE/EV/DNG) or 20 microg EE + 100 microg levonorgestrel (LNG) (EE/LNG). The study was completed by 91 subjects. Blood samples were taken by venipuncture after at least 12 h fasting on Day 21-26 of the control cycle and on Day 18-21 of the first, third and sixth treatment cycle. There was a significant increase in triiodothyronine (T3) and thyroxine (T4) by 20-40% in all treatment cycles, while thyroid-stimulating hormone was significantly increased only with EE/EV/DNG. Treatment with the DNG-containing OCs caused no change in free T4 (FT4) and a transitory reduction in free T3 (FT3) levels during the first cycle. During intake of EE/LNG, FT4 rose slightly, while FT3 was not altered. The pronounced rise in the serum concentrations of cortisol appeared to be related to the EE dose. During the first three cycles of treatment, no effect on angiotensin II levels was observed, while in the sixth cycle a significant decrease was measured in all treatment groups. The four OCs did not influence the serum concentrations of endothelin-1 and no consistent effects were found concerning those of aldosterone. The results suggest that the three DNG-containing and the LNG-containing low-dose OCs may increase T3, T4 and cortisol due to an elevated binding to serum globulins, while the free proportion of the hormones is not or only slightly changed. Therefore, these OCs have only minor effects on thyroid function, adrenal and blood pressure serum parameters.

Effect of four different oral contraceptives on various sex hormones and serum-binding globulins.

In a double-blind, controlled, randomized, four-arm, bicentric clinical study, the effect of four oral contraceptives (OCs) on various hormone parameters and serum-binding globulins was investigated. Four groups with 25 volunteers each (18-35 years of age) were treated for six cycles with monophasic combinations containing 21 tablets with either 30 microg ethinylestradiol (EE) + 2 mg dienogest (DNG) (30EE/DNG), 20 microg EE + 2 mg DNG (20EE/DNG), 10 microg EE + 2 mg estradiol valerate (EV) + 2 mg DNG (EE/EV/DNG) or 20 microg EE + 100 microg levonorgestrel (LNG) (EE/LNG). The study was completed by 91 subjects. Blood samples were taken after at least 12 h of fasting on Day 21-26 of the preceding control cycle and on Day 18-21 of the first, third and sixth treatment cycle. The serum concentrations of free testosterone were significantly decreased by about 40-60% in all four groups, while those of dehydroepiandrosterone sulfate (DHEAS) showed a time-dependent decrease during treatment. Except for EE/EV/DNG, which increased prolactin significantly during the third and sixth cycles, no change was observed with the EE-containing preparations. There was a significant increase in the levels of serum-binding globulins during treatment, which differed according to the composition of the OCs used. The rise in sex hormone-binding globulin (SHBG) was highest during intake of 30EE/DNG (+320%) and lowest with EE/LNG (+80%), while the effect of 20EE/DNG and EE/EV/DNG was similar (+270%). The thyroxine-binding globulin (TBG) levels increased significantly, by 50-60%, during treatment with the DNG-containing formulations, while the effect of EE/LNG was less significant (+30%). The rise in corticosteroid-binding globulin (CBG), which occurred in all groups, was most pronounced in women treated with 30EE/DNG (+90%) and least with EE/EV/DNG (+55%), indicating a strong influence of EE and no effect of the progestogen component. In all treatment groups, the frequency of intracyclic bleeding rose in the first treatment cycle and decreased thereafter. Cycle control was significantly better with 30EE/DNG or EE/LNG than with 20EE/DNG or EE/EV/DNG. There was no significant change in blood pressure, body mass index or pulse rate throughout the study. In conclusion, the DNG-containing OCs caused a higher rise in SHBG and TBG levels than the LNG-containing preparation. The effects on CBG suggest a lesser hepatic effect of 2 mg EV as compared to 20 or 30 microg EE. In contrast to EE, the use of estradiol in OCs appeared to increase prolactin release, while the cycle control was better with the OC containing 30 microg EE.

Effect of dienogest-containing oral contraceptives on lipid metabolism.

In a double-blind, controlled, randomized, four-arm, bicentric clinical study, the effect of four oral contraceptives (OCs) on lipid metabolism was investigated. Four groups composed of 25 volunteers each (mean age 26.1 +/- 4.5 years; body mass index 21.9 +/- 2.8 kg/m(2)) were treated for six cycles with monophasic combinations containing 21 tablets with either 30 microg ethinyl estradiol (EE) + 2 mg dienogest (DNG) (30 EE/DNG), 20 microg EE + 2 mg DNG (20 EE/DNG), 10 microg EE + 2 mg estradiol valerate (EV) + 2 mg DNG (EE/EV/DNG), or 20 microg EE + 100 microg levonorgestrel (LNG; EE/LNG). The study was completed by 91 women. Blood samples were taken by venipuncture after at least 12 h fasting on Days 21-26 of the control cycle and Days 18-21 of the first, third, and sixth treatment cycle. There were clear differences between the effects of EE/LNG and the formulations containing estrogens and DNG. Although EE/LNG did not change the triglycerides levels, a significant increase was observed during treatment with the DNG-containing preparations. Although EE/LNG significantly reduced HDL-CH and HDL(2)-CH, there was a nonsignificant increase with the DNG-containing OCs. No change was observed in the levels of HDL(3)-CH. A significant rise in apolipoprotein A1 occurred during intake with the three DNG-containing formulations, but not with EE/LNG. In contrast to the women treated with combinations of estrogens and DNG, apolipoprotein B rose significantly in the women in the EE/LNG group. Lipoprotein (a) was significantly reduced by 30 EE/DNG and EE/LNG and remained unaltered with 20 EE/DNG and EE/EV/DNG. Altogether, the changes in lipid metabolism caused by the DNG-containing formulations appeared to be more favorable than those observed with EE/LNG. In OCs with DNG, the EE dose does not seem to play a major role with respect to the effect on lipids.

Hemostatic effects of high-dose megestrol acetate therapy in patients with advanced gynecological cancer.

Effects of high-dose megestrol acetate on blood coagulation and fibrinolysis were investigated in patients with gynecological (n = 13) and breast (n = 10) cancer. Patients received either 160 mg or 320 mg/day megestrol acetate orally. Blood sampling was performed prior to and after months 1, 3 and 6 of treatment. Pretreatment values of global clotting times, fibrinogen, factor VII, thrombin-antithrombin III complex, anticoagulation, fibrinolysis and antifibrinolysis were found to be within the reference range. Elevated plasma levels were demonstrated for prothrombin fragments 1 and 2, fibrin degradation products and the plasmin-antiplasmin complex. We demonstrated a significant 20-30% reduction of factor VII until the 3rd month of therapy. No further effects were seen within the remaining 3 months of treatment. For the other analyzed parameters of hemostasis, no significant influence of high-dose progestin treatment was found. Furthermore, we observed no clinically relevant differences between the two dosages. Our results do not provide any evidence that there is a thrombogenic effect of high-dosage megestrol acetate with 160 mg or 320 mg per day amongst patients with advanced gynecological malignancies. The observed incidence of thrombosis might be the consequence of other risk factors such as tumor-induced hypercoagulability, simultaneous chemotherapy or other individual thrombosis risk factors.

[Liposuction for "body contouring" in gynecology]. / Der Einsatz der Liposuktion zum "body contouring" in der Gynäkologie.

OBJECTIVES: The aim of this study was to describe the possible use of the ultrasound-assisted liposuction and liposuction with the tumescent technique for the contouring and remodelling of superficial fat areas of women in the field of gynaecology. PATIENTS AND METHODS: Between 1997 and 1999 85 healthy female patients underwent a liposuction in the department of gynaecology of the university of Essen. The patients were divided into two groups. Thirty patients (group 1) underwent an ultrasound-assisted liposuction whereas the remaining 55 patients (group 2) were operated using only the tumescent technique. RESULTS: From the operated 582 body areas a large volume liposuction with the aspiration of more than 1,000 cc fat was performed in 48.2% of the cases. In the remaining 51.8% of the cases aspiration volumes between 300 and 1,000 cc fat were obtained. No statistically significant differences could be observed when comparing the aspirat volumes between both treatment groups (p > 0.05). Serious complications were not observed. DISCUSSION: Our data could show, that liposuction is an extremely safe method for eliminating surperficial fat depots in the sense of body contouring in gynaecology, but that it should not be used for the reduction of obese body volumes. If ultrasound-assisted liposuction is really superior to liposuction with the tumescent technique remaining uncertain, no time gain could be observed due to this technique.

Cyclic progestin therapy for the management of mastopathy and mastodynia.

The management of benign diseases of the breast aims to halt the progression of fibrocystic transformation and to eliminate the symptoms of pain and breast tenderness. Progestins can be used for this purpose. In a controlled, randomized, double-blind, parallel-group study we treated 31 women with mastopathy/mastodynia with the progestins medrogestone (10 mg/day) or dydrogesterone (10 mg/day) from day 14 to day 25 for six cycles. Before, during and at the end of therapy the following parameters were evaluated: subjective symptoms (pain, tenderness, impairment of daily activities), palpatory findings, sonographic diagnosis and sex hormone profiles. Cyclic administration of the low-dose progestins medrogestone and dydrogesterone proved to be an effective and safe treatment of mastodynia and mastopathy. The objective parameters palpatory findings and sonographic imaging of breast nodules and cysts improved in more than 50% of patients. Improvement was particularly marked in women with low progesterone levels in the second half of the cycle. After six treatment cycles, 75% of the patients treated with dydrogesterone and 86% of the patients treated with medrogestone were completely pain-free.

The effect of tranexamic acid on the quality of life of women with heavy menstrual bleeding.

OBJECTIVE: To investigate whether medical treatment with tranexamic acid would increase the quality of life of women with heavy menstrual bleeding. STUDY DESIGN: This open, uncontrolled usage study included 849 women diagnosed with heavy menstrual bleeding and considered eligible for tranexamic-acid treatment. The condition of the women was investigated at baseline and after the first and the third treated menstruation. Quality of life and subjectively experienced state of health were assessed with the aid of a questionnaire. Satisfaction with the treatment was registered. RESULTS: After the third menstruation, 80% of the women were satisfied with the treatment. Impairment of social activities and impairment at work were greatly reduced by the treatment. Substantial improvements were also recorded with regard to alertness, productivity, cleanliness, spirits, action radius and overall well-being. Adverse reactions to the drug used for the treatment were few and non-serious. CONCLUSIONS: Medical treatment with tranexamic acid increases quality of life for women with heavy menstrual bleeding.

Hemostatic effects of third- and second-generation oral contraceptives: absence of a causal mechanism for a difference in risk of venous thromboembolism.

Some observational studies have found a difference in the risk of nonfatal venous thromboembolism (VTE) with low-dose, oral contraceptives (OCs) containing desogestrel (DSG) or gestodene (GSD) and those containing levonorgestrel (LNG). However, this does not agree with current pathophysiological concepts. This review compares all 17 comparative studies on the hemostatic effects of DSG/GSD- and LNG- or norgestimate (NGM)-containing OCs, and comments on two recent cross-sectional studies on the effects of third- and second-generation OCs on activated protein C (APC) sensitivity. In the comparative studies, the only difference in hemostatic parameters between DSG/GSD- and LNG- or NGM-containing OC users was a tendency towards higher factor VII (FVII) levels with DSG/GSD OCs. Differential effects on APC sensitivity were observed with the endogenous thrombin generation potential (ETP) assay, but not with the classical APC resistance test. FVII is not a risk marker for VTE, but is affected by dietary fat, estrogens and androgens and may interfere with the ETP assay. As no differences in established VTE risk markers were observed, there is no plausible reason for a differential risk of VTE with DSG/GSD- and LNG-containing OCs. In fact, the lack of differences with regard to established risk markers of VTE gives further support to the findings of the most recent epidemiological studies, which have not found any difference in the risk of VTE between third- and second-generation OCs.

Occlusive vascular diseases in oral contraceptive users. Epidemiology, pathology and mechanisms.

Despite being an unprecedented departure from normal physiology, the combined oral contraceptive is not only highly effective, but it also has a remarkably good safety record. Concerns over safety persist, though, particularly with regard to venous thromboembolism (VTE), stroke and myocardial infarction (MI). Epidemiological studies consistently show an increase in risk of VTE, but the results are more contentious with regard to arterial diseases. Despite 40 years of research, the mechanisms behind these adverse effects are not understood. In this review, we integrate information from published studies of the epidemiology and pathology of the occlusive vascular diseases and their risk factors to identify likely explanations for pathogenesis in oral contraceptive users. Oral contraceptives induce both prothrombotic and fibrinolytic changes in haemostatic factors and an imbalance in haemostasis is likely to be important in oral contraceptive-induced VTE. The complexity of the changes involved and the difficulty of ascribing clinical significance has meant that uncertainty persists. A seriously under-researched area concerns vascular changes in oral contraceptive users. Histologically, endothelial and intimal proliferation have been identified in women exposed to high plasma estrogen concentrations and these lesions are associated with thrombotic occlusion. Other structural changes may result in increased vascular permeability, loss of vascular tone and venous stasis. With regard to arterial disease risk, epidemiological information relating to dose effects and joint effects with other risk factors, and studies of pathology and changes in risk factors, suggests that oral contraceptive use per se does not cause arterial disease. It can, nevertheless, synergise very powerfully with subclinical endothelial damage to promote arterial occlusion. Accordingly, the prothrombotic effects of the oral contraceptive estrogen intervene in a cycle of endothelial damage and repair which would otherwise remain clinically silent or would ultimately progress - in, for example, the presence of cigarette smoking or hypertension - to atherosclerosis. Future work in this area should focus on modification of the effects of established risk factors by oral contraceptive use rather than modification of the supposed risk of oral contraceptive use by established risk factors. Attempts to understand vascular occlusion in oral contraceptive users in terms of the general features of VTE or with reference to atherosclerosis may be limiting, and future work needs to acknowledge that such occlusions may have unique features. Unequivocal identification of the mechanisms involved would contribute considerably to the alleviation of fears over vascular disease and to the development of even safer formulations.

Effects of tibolone and continuous combined hormone replacement therapy on parameters in the clotting cascade: a multicenter, double-blind, randomized study.

OBJECTIVE: To determine the effects of tibolone and continuous combined HRT (ccHRT) on parameters in the clotting cascade. DESIGN: Randomized, double-blind study. SETTING: Hemostasis unit of a university hospital clinic in Germany. PATIENT(S): Sixty healthy postmenopausal women. INTERVENTION(S): Twenty-nine subjects were treated with tibolone (2.5 mg/d) and 31 with oral ccHRT containing estradiol (2 mg/d) + estriol (1 mg/d) + norethindrone acetate (1 mg/d). MAIN OUTCOME MEASURE(S): Effects on parameters in the clotting cascade at baseline and after 12 and 24 weeks of treatment. RESULT(S): Tibolone increased fibrinolysis parameters without significantly altering coagulation parameters. Treatment with ccHRT resulted in a stimulating effect on parameters of both fibrinolysis and coagulation. Tibolone showed a stronger reduction of factor VII activity; less reduction of AT-III, protein C activity, and protein S activity; stronger increase of the activated partial thromboplastin time, plasminogen and plasminogen-antiplasminogen complexes; and less increase of D-Dimer than ccHRT. Both preparations similarly reduced climacteric complaints, whereas tibolone showed less breast complaints than ccHRT. CONCLUSION(S): This study confirms that tibolone, and to a lesser extent also ccHRT, changes hemostasis parameters toward a more fibrinolytic profile, which may diminish the risk of venous thrombosis.

Adjuvant CMF-chemotherapy and haemostasis. Effect of "classical" and "modified" adjuvant CMF-chemotherapy on blood coagulation fibrinolysis in patients with breast cancer.

Effects of "classical" and "modified" adjuvant CMF-chemotherapy on haemostasis were studied in 22 patients with breast cancer receiving cyclophosphamide (100 mg/m2 p.o.; days 1-14 or 600 mg/m2 i.v.; days 1,8), methotrexate (40 mg/m2 i.v.; days 1,8) and 5-fluorouracil (600 mg/m2 i.v.; days 1,8). Blood collection was done prior to chemotherapy on day 1 and 8. A significant decrease of protein C antigen and activity associated with cumulative effects was observed from day 1 to 8. This effect was similar with "classical" and "modified" CMF-chemotherapy but the reduction of protein C was more pronounced with the oral application of cyclophosphamide. In absence of any significant cumulative decrease of other vitamin K-dependent blood coagulation proteins (factor VII, protein S), the simultaneous decrease of protein C activity and antigen indicates a specific influence of CMF-chemotherapy on vitamin K-dependent protein C-synthesis in the liver.

[Non-contraceptive benefits of the pill--an often neglected fact]. / Nicht-kontrazeptiver Nutzen der Pille--ein oft unbeachteter Fakt.

While rare cardiovascular risks of oral contraceptives (OCs) caused a lot of concern among OC-using women in the recent past, little attention has been paid in the public to the non-contraceptive benefits of OCs. Short, medium and long term non-contraceptive benefits have to be considered. The early Anglo-American cohort and case-control studies demonstrated a reduction of menstrual complaints, iron-deficiency anaemia, ectopic pregnancies, and a partly drastic reduction of some benign and malignant tumours such as endometrial and ovarian cancer. A risk reduction of rheumatoid arthritis is discussed controversially. The present paper gives an overview of the state of knowledge. For newer OCs with different composition, comparable studies are lacking. Therefore, a cohort study was initiated in Germany in April 1998 to investigate these associations as well for newer OCs, which is presented. The described non-contraceptive benefits should be considered in the benefit-risk assessment when prescribing OCs.

[German Cohort Study of Women's Health--benefits of oral contraceptives. Study protocol]. / Die Deutsche Kohortenstudie zur Frauengesundheit--Zum Nutzen von oralen Kontrazeptiva. Ausführungen zum Studienprotokoll.

This publication is about the study protocol of the German Cohort Study on Women's Health. The main objective is to investigate medical benefits of a long-term oral contraceptive use. The design is an analytical cohort study based on inquiries. Additional cases will be recruited to analyse rare events in separate case-control studies. Voluntary participants who signed to participate in a long-term study are included. An annual drop-out rate of 15% is expected. Study variables encompass personal characteristics, lifetime history of diseases, but also disturbances of the state of health, and quality of life. It is anticipated to achieve 400,000 women-years of observation by 2001 (historic and concurrent follow-up). The study started April 1, 1998 and the current financial phase finishes December 31, 2001. 6000 participants were recruited until December 1998 equivalent to about 190,000 observation-years. Until the end of 1999, an additional 70,000 women-years should be included. There have been many suggestions from participants' to include additional issues of women's health into the study.