Pregnancy (including puerperium) is a period of hypercoagulability and seems to be an independent major risk factor for venous thromboembolism (VTE). However, the basis of the increased risk of VTE in pregnancy and around delivery is unknown. We hypothesized that changes in PRL, which is a prominently increased hormone during pregnancy and lactation, might be involved in the activation of platelets. To investigate platelet functional abnormalities in pregnancy, we assessed the ADP-stimulated and nonstimulated P-selectin expression of platelets in 42 consecutive pregnant women, 22 normo- and hyperprolactinemic patients with pituitary tumors, and controls. In addition, the aggregation of platelets by human PRL in vitro was studied. We found a significant correlation between PRL values and ADP stimulation of platelets in pregnant women (r = 0.56; P < 0.0001) and patients with pituitary tumors (r = 0.57; P = 0.006). Hyperprolactinemic pregnant women or hyperprolactinemic patients with pituitary tumors revealed significantly higher ADP stimulation of platelets (P < 0.0001) than healthy controls or normoprolactinemic patients with pituitary tumors. These results were reconciled by increased in vitro stimulation and aggregation of platelets using human PRL. Our novel findings demonstrate that hyperprolactinemia causes increased platelet aggregation via ADP stimulation both in vitro and in vivo. Moreover, our data indicate that PRL may be a physiological cofactor of the delicate coagulation balance during pregnancy and puerperium that might explain the increased risk of VTE in pregnant women around delivery. Further studies of the interaction between PRL and platelets will clarify the clinical relevance of hyperprolactinemia as a potential risk factor for VTE.

Total mesometrial resection (TMMR) is characterized by: i) the en bloc resection of the uterus, proximal vagina, and mesometrium as a developmentally defined entity; ii) transection of the rectouterine dense subperitoneal connective tissue above the level of the exposed inferior hypogastric plexus; and iii) extended pelvic/periaortic lymph node dissection preserving the superior hypogastric plexus. Since July 1998 we have studied prospectively the outcome in patients treated with TMMR for cervical carcinoma FIGO stages IB, IIA, and selected IIB. By July 2002, 71 patients with cervical cancer stages pT1b1 (n = 48), pT1b2 (n = 8), pT2a (n = 3), pT2b (n = 12) had undergone TMMR without adjuvant radiation. Fifty-four percent of the patients exhibited histopathologic high risk factors. At a median observation period of 30 months (9–57 months) two patients relapsed locally, two patients developed pelvic and distant recurrences and two patients only distant recurrences. Three patients died from their disease. Grade 1 and 2 complications occurred in 20 patients, no patient had grade 3 or 4 complications. No severe long-term impairment of pelvic visceral functions related to autonomic nerve damage was detected. Based on these preliminary results, we believe TMMR achieves a promising therapeutic index by providing a high probability of locoregional control at minimal short and long-term morbidity.

Recently, an increased risk of venous thromboembolism in patients on antipsychotic drugs has been reported, but the molecular etiology is still unknown. Most antipsychotic drugs act as dopamine antagonists, and some of them cause hyperprolactinemia. Hyperprolactinemia has recently been found to cause increased platelet activation via potentiating ADP effects on human platelets. We assessed prolactin values as well as ADP-stimulated and thrombin receptor activator 6-stimulated expression of the platelet activation marker P-selectin in 20 consecutive patients under therapy with antipsychotic drugs. We detected a significant correlation between prolactin values and ADP-stimulated P-selectin expression on platelets in patients on antipsychotic drugs, revealing a significant higher platelet stimulation in hyperprolactinemic patients on antipsychotic drugs than in normoprolactinemic controls. Therefore, hyperprolactinemia might be the yet unknown acquired risk factor in patients on antipsychotic drugs explaining the increased risk for venous thromboembolism in these patients.

In most cases, the endometrioid adenocarcinoma of the endometrium is preceded by hyperplasia with different risk of progression into carcinoma. The original histologic slides from 560 consecutive cases with complex and atypical hyperplasia were re-examined to assess the interobserver-correlation. The hyperplasias were analyzed separately for their likelihood of progression to carcinoma in patients with and without progestogen hormonal therapy. In all cases, a fractional re-curreting was performed to establish the state of the disease.The leading symptom was vaginal bleeding in 65.5% of the cases in the postmenopausal period. Eighty-six percent of the patients presented with obesity (BMI > 30 kg/m2), 23% had had an exogeneous use of estrogens. Twenty-two cases were reclassified as simple hyperplasia and excluded from further analysis. The interobserver-correlation was 91% for complex, 92% for atypical hyperplasia, and 89% for endometrioid carcinoma, representing an overall correlation of 90%. Two percent of the cases with complex hyperplasia (8/390) progressed into carcinoma and 10.5% into atypical hyperplasia. Fifty-two percent of the atypical hyperplasias (58/112) progressed into carcinomas. In the case of progestogen treatment (n = 208; P < 0.0001) 61.5% showed remission confirmed by re-curetting, compared with 20.3% of the cases without hormonal treatment (n = 182; P < 0.0001).Endometrial hyperplasia without atypia is likely to respond to hormonal treatment. Especially in postmenopausal situation, atypical hyperplasia should be treated with total hysterectomy.

Thyrotropin (TSHR) receptor antibodies that bind to the TSHR without stimulating the TSHR have been identified with a direct binding assay. Moreover, TSHR antibodies that exhibit thyroid epithelial cell stimulation without inhibition of 125I-bovine thyrotropin (bTSH) binding and vice versa have been described. These data suggest that stimulation or blocking of the TSHR by stimulating (TSAB) or blocking (TSBAB) TSHR antibodies could be possible without detectable bTSH-displacement activity. However, to date, possible differences between TSAB or TSBAB activity and inhibition of 125I-bTSH binding have not been systematically investigated. Therefore we compared inhibition of 125I-bTSH binding and TSAB or TSBAB activity of sera from 113 patients with Graves' disease treated with antithyroid drugs. To exclude the different assay conditions of previous investigations as possible confounding factors, we determined TSAB or TSBAB and inhibition of 125I-bTSH binding (TBIIW) with the same Chinese hamster ovary (CHO) cells expressing the human TSHR. Furthermore inhibition of 125I-bTSH binding was also determined as thyrotropin-binding inhibitory immunoglobulin (TBII) with solubilized porcine thyroid membranes (TRAK, Brahms, Berlin Germany) and the highly sensitive recombinant human TSH receptor assay (hTRAK, Brahms, Berlin Germany). Only 78% (54/69) of TSAB-positive and 78% (21/27) of TSBAB-positive sera detected with JP26 cells exhibit inhibition of 125I-bTSH binding measured as TBII or TBIIW. Furthermore, 59% (10/17) of sera without TSAB and TSBAB activity revealed inhibition of 125I-bTSH binding measured as TBII or TBIIW. We found significant differences between TSHR bioactivities (TSAB or TSBAB) and inhibition of 125I-bTSH binding. Moreover, there was no agreement between the detectable TSHR bioactivities (TSAB or TSBAB) and their detectable inhibition of 125I-bTSH binding. Therefore, it is very likely that TSH displacement by TSHR antibodies and stimulation or blocking of the TSHR by TSHR antibodies are different functions that do not need to occur together.