Platelet indices in SGA newborns.

PURPOSE: The current study objective was to compare blood platelet indices in full-term small-for-gestational-age newborns (SGA) and full-term appropriate-for-gestational-age newborns (AGA). MATERIALS/METHODS: We introduced to our study 61 SGA newborns (31 females and 30 males) and 70 eutrophic infants (32 females and 38 males). The SGA newborns were divided into two groups: those weighing less than the 5th centile: 35 infants (16 females and 19 males) and those between the 5th and 10th centiles: 26 infants (15 females and 11 males). Platelet indices were estimated in blood samples collected from the umbilical artery. RESULTS: SGA demonstrated a decreased count of blood platelets (238×103/µ) as compared with AGA (286×103/µL), p=0.0001. Platelet hematocrit (PTC) also showed differences in both groups (SGA=0.19% vs. AGA=0.22%; p=0.0005). Mean platelet volume (MPV) was higher in SGA (8.25fl) as compared with AGA (7.84fl); p=0.008. Large platelet count (LPLT) was higher in AGA 6.26% vs. SGA=4.75%; p=0.01. Platelet distribution width (PDW) was found to be nearly the same (SGA=47%, AGA=46%). PDW was higher in SGA newborns < 5th centile (43%) as compared with SGA infants between the 5th and 10th centiles (52%); p=0.008. CONCLUSIONS: A decreased blood platelet count, platelet hematocrit and large metabolically active platelet count, which in addition to reduced synthesis and excessive consumption of coagulation factors in states of hiperclotting is characteristic of IUGR, enhances the possibility of bleeding complications and increases the risk of infections. From a clinical point of view, it is important to take into consideration the degree of intrauterine hypotrophy during the evaluation of hemostatic disorders.

The effect of combined tocolysis on in vitro uterine contractility in preterm labour.

PURPOSE: Animal models have confirmed high efficiency of combined tocolytic treatment in preterm labour. In humans, the recommended doses of tocolytic drugs prolong pregnancy in threatened preterm labour. The aim of the study was to evaluate the inhibitory effect of dual combinations of atosiban, nifedipine and celecoxib on human myometrial strips contractility on the in vitro model of preterm labour. MATERIAL/METHODS: Two groups of patients who delivered by cesarean section were involved in the study: 36 patients who delivered preterm between the 24(th) and 34(th) week of pregnancy and 40 patients who delivered at term. Myometrial samples were obtained from the lower uterine segment during cesarean sections. Contractile activity was recorded with digital software for each drug combination: atosiban/nifedipine; atosiban/celecoxib, nifedipine/celecoxib. Tocolytic efficiency of the drug combinations was assessed using IC(50) parameter - a molar drug concentration inhibiting 50% of contractility. RESULTS: The atosiban/nifedipine combination has shown additive tocolytic effect on myometrial strips contractility in preterm and term patients. The other combinations: atosiban/celecoxib and nifedipine/celecoxib presented only antagonistic effects in both studied groups. CONCLUSIONS: The effect of the combined therapy on human myometrial contractility presented in the study could be a base for further in vivo clinical trials.

A role of thymidine phosphorylase and P53 tissue protein expression in biology of endometrial cancer.

Tumor suppressor gene p53, the most commonly mutated gene in human cancers has been shown to play an important role in the biology of gynaecological carcinomas. Thymidine phosphorylase is one of the most important angiogenic factors, which is connected with tumor expansion and invasiveness. The aim of the study was an evaluation of thymidine phosphorylase and p-53 tissue protein expression in human endometrial cancer cells by immunohistochemistry and comparison obtained data with clinicopathological factors as FIGO stage of disease and histopathologic grade. Endometrial cancer specimens were obtained from 55 postmenopausal patients (aged 52 to 74 years) operated by total abdominal hysterectomy with bilateral salpingo-oophorectomy. None of patients received preoperative pelvic irradiation. Histopathological typing and grading of the endometrial tumors (G-1, G-2, G-3) as well as myometrial invasion (<1/2, >1/2) were assessed using standard criteria, on hematoxylin-eosin sections. FIGO clinical stage of disease was determined. at the surgery. Thymidine phosphorylase overexpression was observed in 23 (41,8 %) cases. Although we found no statistically significant differences in TP expression between histopathologic grades, particular FIGO stages showed a significant trend of increase TP tumor overexpression. P53 protein overexpression was observed in tumor tissue in 21 cases (35,2%). It tended to be more frequent in cases of advanced disease as well as in low differentiated tumors. Although we found no statistically significant differences in p53 gene expression between groups of FIGO stage and histopathologic grade, we obtained a significant trend of increasing the P53 positive rate with both FIGO and tumour differentiation grading Joint assessment of thymidine phosphorylase and tumor suppressor genes expression may be of additional value in determining the biology of endometrial carcinoma. Key words: endometrial cancer, thymidine phosphorylase, p-53.

Evaluation of tumor angiogenesis and thymidine phosphorylase tissue expression in patients with endometrial cancer.

The formation of new blood vessels in endometrial cancer tissue is a main process, which leads to tumor progression, and is connected with tumor expansion and invasiveness. The aim of the study was evaluation of thymidine phosphorylase protein (TP) expression in human endometrial cancer cells by immunohistochemistry and comparison obtained data with intensity of angiogenesis process and clinicopathological factors as FIGO stage of disease and histopathologic grade. Endometrial cancer specimens were obtained from 55 postmenopausal patients (aged 52 to 74 years) underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy. None of patients received preoperative pelvic irradiation. Histopathological typing and grading of the endometrial tumors (G-1, G-2, G-3) as well as myometrial invasion (<1/2, >1/2) were assessed using standard criteria, on hematoxylin-eosin sections. At the surgery, FIGO clinical stage of disease was determined. Thymidine phosphorylase overexpression was observed in 23 of 55 (41.8%) cases of endometrial cancer. Although we found no statistically significant differences in TP expression between histopathologic grades, particular FIGO stages showed a significant trend of increase TP tumor overexpression. Thymidine phosphorylase overexpression cases demonstrate higher intensity of angiogenesis in comparison to negative samples and results are statistically significant for t-test (p<0.0001). The most intensive new blood vessel formation was observed in G-2 of tumor differentiation grade (p=0.013 for ANOVA test) Mean angiogenic points density (APD) values in cases of G-1 histopathologic grade reached 135.7; values of G-2 and G-3 grades reached 213.8 and 162.8, respectively. Mean intensity of angiogenesis in the first FIGO stage of disease reached 160.0 APD, in stage II 205.6 APD, and in the third 286.9, respectively. Angiogenesis was more intensive in cases of advanced tumors - analysis of variance (ANOVA) confirmed statistically significant differences in APD values between FIGO stage groups (p=0.0007). In conclusion, thymidine phosphorylase expression correlates with increased microvessel density in endometrial cancer. The intensity of angiogenesis process increases according to FIGO stage of disease, which is connected with progressing of cancer disease. Thymidine phosphorylase can play an important role in endometrial cancer progression and could offer additional information about advance of disease.

Evaluation of angiogenesis, p-53 tissue protein expression and serum VEGF in patients with endometrial cancer.

Endometrial carcinoma occurs mostly in post-menopausal women. Classical methods of prognostication, as FIGO stage and histopathologic grade, could be improved by applying additional techniques, utilizing molecular biology and immunochemistry. p-53 tumor suppressor gene, the most commonly mutated gene in human cancers has been shown to play an important role in the biology of gynecologic carcinomas. Angiogenesis, a process of formation of new vessels, being connected to tumors progression and metastatic potential was shown to be linked with tumor suppressor genes expression. The aim of the study was to evaluate relationships between intensity of tumor angiogenesis, serum levels of Vascular Endothelial Growth Factor (VEGF) and tissue p-53 protein expression in endometrial adenocarcinoma. Angiogenic Point's Density (APD) was calculated in hot spots areas using the morphometric appliance. For detection of p53 protein in tumor samples, LSAB + Kit Alkaline Phosphatase (DAKO) was used. VEGF levels were assessed in patient's blood sampled before the operation. Overexpression of p53 protein was found in tumor tissue in 35.2% of cases and mean angiogenic points density was greater in p53 positive cases. Serum levels of VEGF were above the cut off level in 54.5% of patients, in those cases angiogenesis was also elevated. In cases of p53 overexpression, VEGF levels tended to be greater as compared with p53 negative cases. In conclusion, our study demonstrated that angiogenesis was more intensive in p53 positive cases, confirming the hypothesis of tumor suppressor-gene regulation of the process of neovascularization. Serum levels of VEGF were borderline-significantly higher in cases of p53 overexpression, they were also correlated to the angiogenesis. Joint assessment of angiogenesis and tumor suppressor genes expression may contribute to reliable evaluation of the biology of endometrial carcinoma.

Oxytocin and fetal membranes in preterm labor: current concepts and clinical implication.

Preterm birth is associated with up to 90% of perinatal deaths. In spite of numerous clinical and preclinical research programs, its incidence has not changed throughout the past decade. An observation that the oxytocin antagonist atosiban delays preterm labor and is significantly more potent than vasopressin(1a) receptors gave rise to research on the role of vasopressin blockade in tocolysis and vasopressin itself in preterm labor. Successful tocolysis allows the introduction of intrauterine steroid treatment of the fetus, which reduces the chance of developing infant respiratory distress syndrome and intracranial hemorrhage. Fetal membranes, decidua and placenta are considered a possible site of initiation of parturition, both term and preterm. Research on the biology of these tissues may shed new light on current concepts of the pathophysiology of preterm labor. We here present a short review on the role of oxytocin, oxytocin receptor blockade and fetal membranes in preterm labor.

Uterine contractility signals--an introduction to wavelet analysis.

PURPOSE: Analysis of the uterine contractility in the nonpregnant states has provided information about physiological changes during menstrual cycle. There is need to develop methods of recording uterine activity as well as mathematical interpretation of recorded time series. Wavelets are a new powerful tool for signal and image processing. The aim of this study is an introductory view of Fourier (one of the fundamental methods of investigating of biomedical signals) and wavelet transforms applications in the analysis of uterine contractions. MATERIAL AND METHODS: Spontaneous uterine activity of healthy patient and patient with dysmenorrhea was recorded by micro-tip two sensors catheter (Millar Instruments, Inc. USA). After amplification analogue signals were converted to digital. Signals were analysed using Fourier and wavelet transforms. RESULTS: Contrary to the Fourier decomposition, which is global and provides the information integrated over the whole signal, the continuous and discrete wavelet transforms allow to extract local and global variations of the recorded contractions. From the analysis of the coefficients of the wavelet transform we can assess various pattern of propagation: normal propagation, simultaneous propagation and inverted propagation. CONCLUSIONS: This study is the introduction to the wavelet analysis of the uterine contraction signals. Wavelet transform provides insight into the structure of the time series at various scales. It allows to localise changes of the signal in time, providing additional information in comparison with the Fourier transform.

Angiogenesis and Bcl-2 protein expression in patients with endometrial carcinoma.

Considering the particular importance of angiogenesis and tumor suppressor genes expression in solid tumors, angiogenesis and Bcl-2 protein expression were evaluated in order to specify their role in the biology of endometrial carcinoma. Clinical material comprised 66 patients (postmenopausal, aged 52 to 76 years) with endometrial adenocarcinoma. For evaluation of angiogenesis immunohistochemical method was applied using DAKO EPOS Anti-Human Von Willebrand Factor/HRP antibodies. Morphometric method was applied to count angiogenic points (microvessels + single endothelial cells), using a light microscope with morphometric appliance. Angiogenic points density (APD) was defined as the density of AP per square mm. Immunohistochemical staining for Bcl-2 cytosomic protein expression was performed using MoAb124 (dilution 1:80, Dako A/S, Denmark) monoclonal antibodies. The percentage of 10% positive cells was considered as Bcl-2 positive tissue expression. Positive cytoplasmic reaction of Bcl-2 in 51.3% of patients with Stage I endometrial cancer, and in 23.8% and 0% of patients with II and III FIGO stage, respectively, was observed. No relationship between Bcl-2 tissue cytoplasmatic expression and tumor grade was found. However, an inverse correlation between cytoplasmatic expression of Bcl-2 and FIGO stage was observed. The APD (angiogenic points density) was increasing with the clinical (FIGO) stage of endometrial cancer, but it was not observed in the case of tumor histologic grade. Bcl-2 expression and angiogenesis may be a useful parameter in evaluation of the biology of endometrial adenocarcinoma as the study conducted showed the influence of Bcl-2 protein expression upon angiogenesis.

[Birth environmental modification: needs of mother and child in modern obstetrics]. / Modyfikacja srodowiska narodzin--potrzeby matki i dziecka a potrzeby nowoczesnego poloznictwa.

This paper evaluates changes which all ready has been done and still are taking place in obstetrics according to World Health Organisation recommendations in relation to women's increasing expectation from obstetric hospitals and maternity units. The needs of parturients and theirs children are not in contrary to the needs of modern obstetrics. An attempt has been done to disclose concurrent points to work up the best obstetrics health care model after 2000 year. The author emphasizes that progressive technicalization in obstetrics could not indicate its dehumanization.

Corticotrophin-releasing hormone and ACTH levels in maternal and fetal blood during spontaneous and oxytocin-induced labour.

The changes in corticotrophin-releasing hormone (CRH), ACTH and dehydroepiandrosterone (DHEA) in maternal and fetal plasma were estimated in women undergoing spontaneous and oxytocin-induced labour to correlate hormone changes with the mode of parturition. Blood was sampled from a maternal peripheral vein 2 days before labour, during the second stage of labour and on the second postnatal day, and also from umbilical vessels just after delivery. Hormone concentrations were measured by RIA and ELSA methods. The maternal plasma CRH concentration before labour was significantly higher in the group of women delivered spontaneously and declined during the labour through to the second postnatal day. Measured in umbilical vessels, CRH as well as ACTH concentrations were higher in the umbilical vein than artery. The mean maternal plasma ACTH was similar in both groups before delivery, then increased significantly in both groups during the labour, decreasing on the second day after delivery. There were no changes in DHEA concentrations among the groups and at all time points of collection. No correlations between CRH and ACTH or DHEA were observed. Our results suggest that the maternal pituitary can respond to stress factors during delivery but peripheral CRH, probably mainly of placental origin, is not a major modulator of pituitary action.

[The management of labor overweight women with intrapartum fetal oxygen saturation monitoring]. / Sródporodowy nadzór z wykorzystaniem pulsoksymetrii plodowej u rodzacych z nadwaga.

OBJECTIVE: Overweight is one of the most common problems that occurs in pregnancy. The aim of this study was to evaluate the usefulness of fetal pulse oximetry during labour and to compare fetal oxygen saturation between cases with pregravid overweight and normal weight. MATERIAL AND METHODS: Fetal oxygen saturation was continuously recorded with use of Nellcor N-400 fetal pulse oximeter in 20 cases of pregravid overweight and 30 control cases of normal weight. Distribution of fetal oxygen saturation values during 4 periods of labour was analyzed and compared between the examined groups together with neonatal umbilical artery pH values, Apgar score, birth weight and percentage of ceasarian sections performed. RESULTS: We noticed statistically important differences in fetal oxygen saturation between analyzed groups. Mean oxygen saturation value was lower in the overweight group, at the end of first stages of the labour (47% vs 52%) and at the second stages (42% vs 46%) We noticed differences in birth weight too. No significant differences in neonatal umbilical artery pH, ceasarian sections, newborns mean 1 minute Apgar score were observed between analyzed groups. CONCLUSION: Fetal pulse oximetry is a a useful method for intensive surveillance of the fetus at risk of hypoxemia during the labour. A lower fetal oxygen saturation value during labor by pregravid overweight were observed.

Permeability of fetal membranes to calcium and magnesium: possible role in preterm labour.

Calcium (Ca(2+)) and magnesium (Mg(2+)) are co-factors in the synthetic activity of a variety of enzymes and in the secretory process. Both the binding to fetal membranes and the diffusion through the membranes of these two cations could be important factors in the synthesis and/or action of prostaglandins and generation of nitric oxide (NO) which are believed to regulate myometrial activity particularly for the induction of labour. In the present study, the permeability to Ca(2+) and Mg(2+) of chorioamniotic membranes obtained from women who had undergone term or preterm labour was examined. Diffusion of Ca(2+) and Mg(2+) were measured using a system of Plexiglas chambers separated by the mounted fetal membrane. Permeability of Mg(2+) and Ca(2+) through fetal membranes was calculated using non-linear regression analysis. The data show highly significant differences in the diffusion of Ca(2+) and Mg(2+) across fetal membranes between preterm and term labour. Transport coefficient K for Ca(2+) was 0.203 h(-1) and 0. 0223 h(-1) in term and preterm labour respectively. The corresponding values for Mg(2+) were -0.017 h(-1) and 0.051 h(-1) respectively. It is proposed that a considerable reduction in Ca(2+) available to myometrium and placenta would result in down-regulation of nitric oxide synthase (NOS) activity and thereby a reduction in NO production. This together with an effect on intracellular Ca(2+) transport resulting from a reduced availability of Mg(2+) would lead to increased myometrial activity in preterm labour.

[Evidence-based medicine and medical databases in obstetrics and gynecology]. / Medycyna oparta na dowodach i medyczne bazy danych w poloznictwie i ginekologii.

Evidence-based medicine is a new trend in both teaching medicine and supporting the clinical decisive process, answering the clinical questions. The basis of the evidence-based medicine comprises of analysing and interpreting current and reliable medical publications concerning certain subject. The important condition, which has to be fulfilled is a possibility of an easy access to current medical information--via internet, medical publications' databases and publications themselves. It is crucial to use the proper hardware system (local net) and proper software system--tools for using evidence-based medicine. Regarding the medical research, nowadays, database systems became unavoidable. By using such a programs process of data collection, control and analysis became both easier and more reliable thanks to eliminating many "human based" errors. In following paper own experience in introducing evidence-based medicine and medical databases in the field of obstetrics and gynaecology will be presented.

Receptor binding of oxytocin and vasopressin antagonists and inhibitory effects on isolated myometrium from preterm and term pregnant women.

OBJECTIVE: To test binding affinities for, and inhibitory effects on, myometrium of some oxytocin and vasopressin antagonists with respect to their therapeutic potential. DESIGN: Receptor binding studies on transfected cell lines. In vitro contractility studies of human myometrium. SETTING: The Research Laboratory of Sanofi Recherche, Centre de Toulouse, France and the Departments of Obstetrics and Gynecology, Lund University Hospital, Sweden and Bialystok University Hospital, Poland. PARTICIPANTS: Nine women delivered by caesarean section preterm and 37 delivered at term for routine obstetric indications. INTERVENTIONS: The binding affinities of oxytocin, arginine vasopressin, atosiban (1-deamino-2-D-Tyr(OEt)-4-Thr-8-Om-oxytocin), SR 49059 and SR 121463 for the human oxytocin and different subtypes of vasopressin receptors were determined. Concentration-response curves with oxytocin and arginine vasopressin were recorded on myometrium from preterm- and term-delivered women in control experiments and in the presence of 2.5 and 10 nmol/L of SR 49059. Furthermore, using term myometrium, the influence of SR 49059 and SR 121463 in concentrations of 3, 10, 30 and 100 nmol/L on responses to the EC50 concentrations of oxytocin and vasopressin were compared. MAIN OUTCOME MEASURES: Receptor binding affinities. In vitro contractile effects and their inhibitions. RESULTS: Oxytocin had a high affinity for the oxytocin receptor (K(i) in mean = 6.8 nmol/L) and bound, to some extent, to the vasopressin V1a receptor (K(i) = 34.9 nmol/L). Vasopressin displayed higher affinities for vasopressin V1a, V1b and V2 receptors (K(i) = 1.4, 0.8 and 4.2 nmol/L, respectively) than for the oxytocin receptor (K(i) = 48 nmol/L). Atosiban and SR 49059 both had a high affinity for the vasopressin V1a receptor (K(i) = 4.7 and 7.2 nmol/L, respectively, and a moderate one for the oxytocin receptor (K(i) = 397 and 340 nmol/L, respectively). SR 121463 exerted a predominant binding to the V2 receptor (K(i) = 3.0 nmol/L). In the concentration-response experiments levels of up to 10 nmol/L of SR 49059 had no influence on the effect of oxytocin on myometrium from women preterm and at term pregnancy. However, a concentration-dependent inhibition of the responses of both these type of tissues to vasopressin was seen. The effects of EC50 concentrations of oxytocin and vasopressin on term pregnant myometrium were markedly inhibited by 10 nmol/L and higher concentrations of SR 49059, the inhibition of the response to vasopressin being more pronounced than that of the oxytocin response. SR 121463 at maximal concentration only caused slight inhibitions of the oxytocin and vasopressin responses. CONCLUSIONS: Atosiban and SR 49059 both have moderate binding affinities for the human oxytocin receptor and high binding affinities for the vasopressin V1a one. We demonstrated that SR 49059 inhibits the response of term myometrium to oxytocin and that of both preterm and term myometrium to vasopressin. These observations suggest a therapeutic potential of SR 49059 in preterm labour. The vasopressin V2 receptor is apparently not involved to any significant degree in the activation of the pregnant human uterus.

[Evaluation of the effectiveness of a low-dose aspirin in the treatment of intrauterine growth retardation (IUGR)]. / Ocena skutecznosci leczenia hipotrofii plodu przy uzyciu malych dawek kwasu acetylosalicylowego.

OBJECTIVE: To evaluate the benefits of IUGR treatment by low doses of acetylsalicylic acid (ASA) (1.5 mg/kg) compared to the standard method. The study was based on the reports that aspirin at low doses shifts prostacyclin/tromboxan A2 balance to the dominance of prostacyclin by inhibiting cyclooxygenase activity in platelets, which results in the improvement of the utero-placental circulation. MATERIAL AND METHOD: 31 pregnant women with diagnosed fetal IUGR were randomly assigned to two groups, receiving either low-dose ASA (n = 22) or the standard treatment (Sadamin, Partusisten, glucose i.v., amino acids i.v.) for 10 days. Ultrasound examination of the biometric parameters of the fetus (BPD, AC, FL) was performed and estimated fetal weight (EFW) calculated before and after treatment. The birthweight of infants in the two examined groups was compared. RESULTS: The mean increase in EFW was higher in the aspirin-treated group compared to that receiving standard treatment (478 g vs 246 g, p < 0.05). In all the biometric parameters under study a higher increase was noted in the group with aspirin treatment; however, the difference was not statistically significant. The mean birthweight was found to be higher in the ASA group as well (2856 g vs 2511 g). The frequency of small-for-gestational-age (SGA) infants (birth weight below 10th percentile) was lower in the ASA group than in the controls (27% vs 55%). The low-dose aspirin therapy did not produce any adverse side-effects either among mothers of infants. CONCLUSION: The treatment with low doses of aspirin reduces the proportion of SGA babies and increases birthweight in the case of a diagnosed fetal growth retardation. Since the number of subjects in this study was relatively small, further clinical trials are necessary to evaluate the effectiveness of IUGR treatment by low-dose aspirin.

[Molecular markers in ovarian cancer]. / Molekularne markery w raku jajnika.

Within past few years, the investigation of molecular genetic markers has had an increasing influence on clinical decisions about initial treatment and follow-up. This review presents data concerning the most studied and interesting molecular markers in ovarian cancer. p53 tumour suppressor gene, Bcl-2 oncogene, K-ras oncogene, c-erb2 proto oncogene, c-myc oncogene are examples of currently used molecular genetic markers. Some of these markers might be useful adjuncts for monitoring response to therapy, including early detection of tumour reactivation to allow curative therapy and rapid detection of treatment failure. The study of these markers may also lead to a better understanding of the biological characteristics of ovarian cancer. The information derived from studies of these markers also represents the most promising avenue towards new treatment strategies.

Effects of the vasopressin V1a receptor antagonist, SR 49059, on the response of human uterine arteries to vasopressin and other vasoactive substances.

BACKGROUND: Arginine vasopressin (AVP) activates the uterus via V1a receptors and is apparently an important factor for the myometrial hyperactivity, uterine ischemia and pain of primary dysmenorrhea. The orally active and selective, non-peptide AVP1a receptor antagonist, SR 49059, has been shown to inhibit the myometrial action of AVP, but the specific influence of this substance on the effects of AVP and other vasoactive agents on human uterine arteries is unknown. METHODS: Concentration-responses of AVP on isolated medium-sized human uterine arteries were studied after incubation with only vehicle (DMSO, 0.1%) and with SR 49059 in concentrations of 0.5, 2.5 and 10 nmol/L. Furthermore, the concentration-responses of AVP were investigated without and with SR 49059 (2 and 10 nmol/L) on small and medium-sized arteries. Finally, the influence of 2.5 nmol/L of SR 49059 on concentration-responses of endothelin-1, noradrenaline and prostaglandin F2 alpha was studied. RESULTS: The EC50 for AVP on medium-sized arteries was 0.53 +/- 13 nmol/L. SR 49059 caused a competitive, dose-dependent inhibition of AVP-responses, the highest concentration giving an EC50 of 460 nmol/L. The pA2 value was 9.84. The responses of the small artery preparations to AVP, both without and with the antagonist, were more pronounced than those of the medium-sized ones. The vasoconstrictive effects of endothelin-1, noradrenaline and prostaglandin F2 alpha were less pronounced than those of AVP and unaffected by pre-exposure to SR 49059. CONCLUSIONS: The high potency of AVP on human uterine arteries, particularly those of small size, supports an involvement of the peptide in the regulation of uterine blood flow in both physiological and pathophysiological condition. SR 49059 is a potent and selective AVP V1a receptor antagonist in the smooth muscle of human uterine arteries.

Clinical tumour markers in ovarian cancer.

Within past few years, the measurement of serological, histochemical and molecular genetic markers has had an increasing influence on clinical decisions about initial treatment and follow-up. This review presents data concerning the most studied and interesting markers in ovarian cancer. CA 125, CA 19.9, TATI, CASA, CEA, TPA, TPS and CYFRA21-1 are now the most widely used serological tumour markers for management of ovarian cancer patients. Ras oncogenes, C-erb2 proto-oncogene, p53 suppressor gene and Bcl-2 oncogene are examples of currently used molecular genetic markers. As histochemical markers-proliferation markers, flow cytometric analysis, thymidine labelling index, Ki-67 nuclear antigen or differentiation markers are nowadays the ones most often determined. Some of these markers might be useful adjuncts for monitoring response to therapy, including early detection of tumour reactivation to allow curative therapy and rapid detection of treatment failure. The study of these markers may also lead to a better understanding of the biological characteristics of ovarian cancer. Numerous tumour markers characterized in this paper have been recognized as promising prognostic factors. The information derived from studies of these markers also represents the most promising avenue towards new treatment strategies; nevertheless to validate these factors, prospective studies of a large patient population are needed.

Potent inhibition by tamoxifen of spontaneous and agonist-induced contractions of the human myometrium and intramyometrial arteries.

OBJECTIVE: Our purpose was to elucidate the mechanism of direct (nongenomic) action of antiestrogens on spontaneous and agonist-induced contractions of the human myometrium and uterine arteries. STUDY DESIGN: Myometrial strips and pieces of uterine arteries were obtained from nonpregnant premenopausal women undergoing hysterectomy. Spontaneous activity of myometrium and responses of myometrium and artery to K(+)-depolarization and vasopressin were recorded under isometric conditions. Quantification of the responses was done by planimetry. RESULTS: The 50% inhibitory concentration values for tamoxifen, clomiphene, and cyclofenil in the case of myometrial spontaneous activity were 2.8, 43, and 331 nmol/L, respectively. Vasopressin-induced contractions in both the myometrium and arteries were potently inhibited by tamoxifen, and the 50% inhibitory concentration for the myometrium (1.4 nmol/L) was significantly lower (p < 0.05) than that for the arteries (11 nmol/L). Although tamoxifen caused no inhibition of responses induced by high potassium chloride (80 mmol/L), responses induced by low potassium chloride (20 mmol/L) were inhibited by 40% to 50% in both the myometrium and arteries. Glibenclamide reversed the inhibition by tamoxifen of spontaneous myometrial activity. CONCLUSIONS: Tamoxifen is a highly potent inhibitor of the contractile activity of the human nonpregnant myometrium and uterine arteries. It is suggested that tamoxifen could have strong potential in the treatment of dysmenorrhea.

Fibromyomas and uterine contractions.

BACKGROUND: Women with uterine fibromyomas may suffer from dysmenorrhea, menorrhagia or infertility, which all may be due to an effect of the fibroids on uterine activity. The effect of myomectomy on uterine contractility is unknown. METHODS: In women undergoing myomectomy because of dysmenorrhea, menorrhagia or infertility, intrauterine pressure was recorded before and three months after the operation on corresponding days of the menstrual cycle. Records were obtained during spontaneous uterine activity as well as after oxytocin and vasopressin challenge by intravenous bolus injections of 10 pmol/kg body weight. The area under the recording curve (AUC), maximal amplitude of uterine contractions and deformation index of uterine pressure recordings were measured. RESULTS: In six women, in whom recordings could be obtained before and after operation on corresponding days of late follicular phase of the menstrual cycle, the AUC and maximal amplitude of contractions increased after myomectomy. The effect of oxytocin injection also varied, whereas no difference was seen in effect of vasopressin. CONCLUSIONS: It is suggested that women with uterine fibromyomas may have disturbed uterine spontaneous contractions and responsiveness, which may be regulated by myomectomy.