Biomedical subjects
Publications and source records attributed to A E Schindler.
On 9-11 May 1997, the second Meeting of the European Progestin Club was held in Turin, Italy. Aspects of progestin use on the breast were discussed, based on the currently available scientific data. The paper covers topics addressed at the meeting and summarizes the recommendations which could be agreed on by the participants.
OBJECTIVE: A computer based, temperature controlled bipolar coagulation system has been developed. This system was evaluated for its efficiency on electrocoagulation of rabbit uterine horns at a low temperature. STUDY DESIGN: In purpose to find an optimal setting, rabbit uterine horns were coagulated at various temperature and time. They were examined histologically and histochemically up to six weeks after coagulation. RESULTS: Electrocoagulation at 90 degrees C for 30 s induced a total occlusion of the lumen when examined six weeks later. CONCLUSION: This coagulation system with low temperature is sufficient for a total occlusion of uterine lumen in the rabbit.
A multicenter, open-label, compassionate-use trial studied the antiemetic efficacy and tolerability of granisetron in patients who had failed other antiemetic therapies in previous cycles of cytostatic chemotherapy. The antiemetics that had been used previously included metoclopramide, dexamethasone and ondansetron. A total of 517 patients, 456 of whom had failed other antiemetics, were treated in up to 15 successive cycles of chemotherapy. The numbers of patients treated in the first six of these cycles were large enough to allow the drawing of meaningful conclusions from the results. During that period, a complete response was achieved in 53-60% of patients. In addition, antiemetic efficacy was sustained throughout these six repeated treatment cycles. Granisetron was less effective against high-dose cisplatin chemotherapy than against other cytostatic regimens. The treatment was well tolerated--the main adverse events reported were headache and constipation; no serious adverse events were considered to be attributable to the drug. It is concluded that granisetron treatment was effective and well tolerated in patients who had previously failed other antiemetic therapies, including treatment with 5-hydroxytryptamine3 antagonists.
The rare case of a decidualized endometriosis of the appendix vermiformis is reported in a woman who developed HELLP syndrome during the 32nd week of a twin pregnancy. Cesarean section and simultaneous appendectomy were performed. An inspection of the appendix should always be carried out if an endometriosis-associated anamnesis is known. No pathophysiological correlations between the HELLP syndrome and the endometriosis of the appendix vermiformis could be found.
The relationship between thromboembolism and oral contraceptives has been discussed for 30 years. Recently, a new actuality for this problem has grown up. The estrogen component of the preparations seems to be the cause, but some authors also think of the progestogens as responsible for drug-related thromboembolic disorders. In 31 patients with mastopathy or mastodynia, who had been treated with 10 mg medrogeston of dydrogesteron for six cycles, there were no significant changes in the parameters of hemostasis and fibrinolysis. Especially, we did not find any indications to an activation of the coagulation system. There is no evidence for a thrombogenetic effect caused by the cyclic therapy with these progestogens.
Medical oestrogen suppressive therapy has to be considered as an important principle in the management of endometriosis. In the last years GnRHa became the "gold standard" as pre or postoperative measures before/after surgical intervention. We analyzed the data of 198 patients, most of them with recurrent endometriosis histologically confirmed during first-look laparoscopy. Patients were treated in a prospective, multicentre phase III study with the six months GnRHa leuprorelinacetate depot (LAD) followed by a second-look laparoscopy for precise assessment of therapeutic effects. In all stages of endometriosis a 35% reduction of the r-AFS-score compared to the baseline could be achieved due to surgical intervention during first-look laparoscopy with a further improvement of 64% after GnRHa-therapy and surgery during second-look laparoscopy. Two subgroups of patients (24 vs. 45) could be analyzed according to the time of second-look laparoscopy (< or = 30 days vs. > or = 60 days after last injection) showing a comparable r-AFS-score reduction. Both, superficial lesions and deep infiltrating nodules, endometriomas, peritoneal implants and obliterated cul de sac could successfully be treated through the combined medical-surgical approach. Pre- or postoperative therapy with a GnRHa facilitates surgical excision of the implants, a subtle adhesiolysis and often complete removal of all visible lesions. In a high percentage of patients, including advanced stages of the disease, a preservation of ovarian tissue to ensure the childbearing potential could be achieved by minimal-invasive techniques. These results can be claimed as the prerequisites for long-term relief of endometriosis complaints and encouraging pregnancy rates in endometriosis related infertility. This confirms great clinical benefit of the combined medical-surgical approach for the treatment of this enigmatic disease.
Experimental studies in animals and investigations in human beings have demonstrated that an increase of body fat mass and the increase of the waist/hip-ratio raises the risk of endometrial and breast cancer. There are also indications for an influence on ovarian and colon cancer. These effects by adipose tissue are created by endocrine changes such as an increase of total and free estradiol, changes in progesterone secretion, protein binding concentrations, growth factors and receptor action. Besides the increased risk for cancer there is also an effect on prognosis.
Generally, obesity represents a risk factor for pregnancy and birth. Already the conception rate is lowered. If pregnancy occurs, there is an increased abortion rate and an increase of neural tube defects. The efficiency of prenatal diagnosis is decreased by obesity. In obese women pregnancy is more frequently associated with complications such as chronic hypertension, gestosis, disturbances of carbohydrate metabolism, liver- and cardiac dysfunction. Central obesity has the highest risk probability. Also during birth the risk of complications is dependent upon the degree of obesity. This applies to the whole delivery process, operative deliveries and the perinatal mortality. Operative delivery by cesarean section is associated with a higher complication rate compared with pregnant women with normal weight. The postpartal course of body weight has to be controlled particularly in obese women.
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OBJECTIVE: Cellular adhesion molecules ICAM-1 and VCAM-1 have been implicated in tumor progression and metastasis. As the sequential interaction of neoplastic cells with the endothelium of tumor neovascularisation is believed to be essential for tumor metastasizing processes, we analysed the concentration of ICAM-1 and VCAM-1 in the cytosol of patients with human breast cancers and their corresponding sera. We compared the obtained values with established prognostic parameters for breast cancer. Benign breast tissues were also analyzed. PATIENTS AND METHODS: Levels of ICAM-1 and VCAM-1 of 62 patients with invasive breast cancer and 17 patients with benign breast tissue were measured using commercially available sandwich enzyme-linked immunoassays with monoclonal antibodies. To establish a reference and control group, levels of ICAM-1 and VCAM-1 were measured in the sera of 66 women without breast tumors. RESULTS: The mean cytosol concentration of ICAM-1 and VCAM-1 was significantly higher in the breast cancer specimens than in the tissue of patients with benign breast diseases. This could be found not only in the tumor cytosol but also in the corresponding sera of the patients. No correlations between the ICAM-1 and VCAM-1 expressions and established prognostic parameters could be observed. CONCLUSIONS: Our findings suggest that malignant breast cancer cells could induce neovascularisation with subsequent high expressions of ICAM-1 and VCAM-1. These upregulations of adhesion molecules might contribute to changes in invasive phenotypes by promoting endothelial cell adhesion and angiogenesis, as well as being responsible for the recognition of tumor cells by the human immune system. Prognostic relevance for the development of breast cancer could not be established.
After bioptical diagnosis of endometriosis, 81 patients were treated with GnRH-agonists buserelin or leuprolide for six months. Biopsies before and after treatment were used to test a semiquantitative score-system, regarding atrophy of glands and stroma cells. Furthermore glandular diameter, circumference and area of nuclei were examined morphometrically using a microscopic semiautomatical measuring system. Morphometrical and histological alterations during therapy were evaluated. Additionally, data suitable for predicting a possible therapeutic success were described. After therapy 40 patients still showed endometriotic implants (partial responder) in contrast to 41 cases without foci (total responder). Therapeutic effect of GnRH-agonists was proved in every respect: clinical complaints decreased markedly during GnRH-agonists therapy. Both buserelin and leuprolide treated groups revealed increase of atrophy and reduction of extension of stroma. Correspondingly morphometrical analysed parameters such as diameter, circumference and area of glands decreased during therapy as well as area of cytoplasm and nuclei. Except the diameter of glands, the leuprolide treated partial responder group (residual foci after GnRH-therapy) revealed a stronger therapeutic effect than the buserelin treated partial responder group. Obviously this effect seems to be produced by the stronger estradiol suppression of leuprolide. Pretherapeutic comparison of measured values pointed out a minor distinct endometriosis in the total responder group. Success or failure of therapy seems to depend more on the pretherapeutic degree of expression of endometriosis. Obviously the kind of applicated GnRH-agonist plays a minor distinct role. Morphometrical data of endometriotic foci appear to be appropriate to predict a possible therapeutic success of GnRH-agonist therapy. But because of many exceptions only a roughly estimated prediction is possible.
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OBJECTIVE: In our previous study, 119 patients with histologically confirmed endometriosis underwent a 'three-step' therapy between 1987 and 1989, where surgical removal of endometriosis was followed by a 6 month treatment with 3 x 300 microgram buserelinacetate daily intranasally and a second look laparoscopy or laparotomy with removal of residuals. Long-term follow-up data in respect of recurrence of symptoms and pregnancy outcome were investigated. STUDY-DESIGN: Long-term follow-up data of 42 out of 119 treated patients on the post-treatment effect were obtained using a special questionnaire. Recurrence of dysmenorrhea, dyspareunia and pelvic pain was defined as recurrence of disease. The follow-up period was up to 98 months with a median time of 82.5 months. RESULTS: Out of the 42 patients, 23 complained of infertility. Fourteen out of these 23 patients became pregnant during the follow-up period, resulting in 23 pregnancies with 18 newborns, 4 miscarriages and one ectopic pregnancy. Ten patients conceived spontaneously, stimulation program became necessary in the rest of patients. Twenty-eight of the 42 patients complained recurrence of symptoms with median first onset at 10.7 months. Improvement on quality of life and subjective conditions were reported by 30 patients. CONCLUSIONS: Our study suggests that the 'three-step' therapy of endometriosis with GnRH-agonist buserelinacetate leads to a significant improvement on the quality of life and well being in the majority of the patients and to a high pregnancy rate. This treatment represents a favourable approach in the management of endometriosis.
The expression of gap junction connexins (Cx) in the female reproductive tract of rodents and in the human endometrium is highly regulated by steroid hormones. Here we have investigated the distribution and regulation properties of Cx43, Cx26 and Cx32 in the human ectopic endometrium of 41 patients, using immunohistochemistry. The biopsies were obtained during the early or late follicular phase (26 cases), during the corpus luteum phase (five cases) and after a 6 month treatment with a gonadotrophin-releasing hormone (GnRH) agonist (three cases) or progestin (seven cases). Aberrant expression of Cx43 was found in the epithelium of nearly all endometriotic glands whereas Cx26, typical for human uterine epithelium cells, was only detected in 18 cases; in 17 it was co-expressed with Cx43. The stromal compartment of the tissues did not express any connexins investigated. Staining for Cx32 was absent in all endometriotic tissues. Strong expression of Cx43 was correlated with a high serum value of 17 beta-oestradiol, whereas a strong expression of Cx26 was found with high values of progesterone mainly in patients after progestin treatment. The epithelium of endometriotic implants collected after GnRH agonist treatment expressed Cx26 and Cx43 only moderately. The patterns described demonstrate an aberrant connexin expression and a different hormonal regulation pattern in endometriotic tissues compared to the normal cyclic uterine endometrium, thus indicating a high dedifferentiation from the normal situation. However, endometriosis still remains a hormonally-dependent benign disease, and hence, can be treated hormonally.
The aim of this study was to obtain data about the pregnancy rate in patients with uterine leiomyomata after treatment with gonadotropin-releasing hormone (GnRH) agonists followed by myomectomy. Between 1987 and 1993, 61 patients with uterine leiomyomata and sterility underwent 6 months' GnRH agonist treatment, in part with a surgical intervention. Sixty-two per cent of the patients suffered from concomitant endometriosis. After hormonal therapy 41 patients underwent a myomectomy. According to sonographic and clinical criteria, there was no indication for the enucleation of the leiomyomata for the remaining 20 patients. Owing to the combined therapy, consisting of primary treatment of uterine leiomyomata with GnRH agonists, followed by surgical intervention, 25 patients (41%) suffering from long-term sterility (average 4 years) became pregnant. An early abortion occurred in only three cases (12%). No patient who underwent a myomectomy developed new myomata during the following pregnancy. Four patients suffering from a single leiomyoma became pregnant within the first 3 months after myomectomy, all of them conceiving spontaneously. Considering the high rate of spontaneous conceptions and the low abortion and complication rates during pregnancy, the combined therapy of GnRH agonists followed by myomectomy represents a major step forwards in the effective treatment of sterility in patients with uterine leiomyomata.
The histological diagnoses of 109 cystic adnexal masses were compared with the results of ultrasound examination, color, cytology and biochemical analyses of cystic fluid. In cases with suspicious results by ultrasound examination most of the malignant tumors but only a small number of benign cystic masses were found. Macroscopic and cytologic examinations gave no further informations. By biochemical analyses functional cysts could be detected with 86% of sensitivity and 100% of specificity by a combination of estradiol, progesterone and Ca 12-5. Endometrioma and malignant tumors could be separated from other adnexal masses (specificity 95%, sensitivity 100%) with a combination of Tag 72-4 and CASA.
We report a case of parenchymal pulmonary endometriosis in combination with severe endometriosis genitalis externa. The difficulties on the way to final diagnosis are described, also the different possibilities of hormonal treatment that results in ovarian suppression. In our case the patient is without any symptoms since three years using a GnRH-Agonist as first line therapy and as second line therapy high-dose medroxyprogesterone acetate. Because of the very good clinical results after hormonal suppression surgical intervention might become necessary only in certain cases. This can be the case when after intolerance of hormonal treatment angiography of lung vascular system on the bases of number and localization of endometrial lesions shows good operative conditions.
Breast cancer disease and as well as CMF-chemotherapy are associated with an increased risk for thromboembolic complications. There is evidence that effects on the hemostatic system may play an important role. To minimize the impact of tumor associated hypercoagulability, we choose to study CMF-associated effects on the hemostatic system within an adjuvant setting. Blood coagulation and fibrinolysis were examined before and 24 hours after intravenous application of CMF-therapy at 17 patients with breast cancer. 16 parameters of coagulation and fibrinolysis were studied. In a longitudinal analysis covering the complete 6 month treatment period we found a decrease of thromboplastin time (TPZ) factor VII (FVII) and protein C antigen (PC Ag) and activity (PC Act). Clinically relevant pathological results and cumulative effects were observed only for PC Ag and Act, while the mean values of TPZ and FVII returned to pre-treatment levels after each course of treatment. These data suggest a potential impact of CMF-chemotherapy on synthesis and activation of vitamin-K-dependent coagulation factors thus providing a possible explanation for the increased risk for thrombosis during CMF-chemotherapy.