The efficacy of nebivolol on spontaneously hypertensive rats with overactive bladder - an experimental study.

Introduction: Overactive bladder (OAB) is a disease that significantly decreases quality of life. Adverse effects of the drugs currently used in OAB treatment limit their use in patients with hypertension. Nebivolol (a ß1-adrenergic receptor blocker) is approved for hypertension treatment, but also shows agonistic activity on ß3-adrenergic receptor, located in the urinary bladder. The aim of this study was to assess the impact of nebivolol on OAB symptoms and cardiovascular parameters in spontaneously hypertensive rats (SHR) - an animal model of OAB and hypertension. Material and methods: Female Wistar-Kyoto (WHY) and SHR rats were used in the experiments. Nebivolol was administered intra-arterially at a single daily dose of 0.05 mg/kg for 14 days. Subsequently, cystometry and bladder blood flow assessment were performed. Then, 24-hour measurement of heart rate, blood pressure, and urine production was carried out. In addition, the bladders of experimental rats were removed and processed to conduct biochemical analyses. Results: The main finding of this study is that the treatment with nebivolol resulted in an improvement of cystometric parameters characteristic for OAB in SHR. Nebivolol normalised blood pressure in SHR, while in WHY the cardiovascular parameters remained unchanged. Biomarkers characteristic for OAB were elevated in SHR compared to WHY, and nebivolol decreased their values in SHR while it had no influence on WHY. Conclusions: Nebivolol alleviates OAB symptoms and normalises blood pressure in SHRs. These results suggest that nebivolol may be a useful treatment alternative for OAB patients with pre-existing hypertension.

The Lublin Protocol of the Uterine Arteries Embolization in the Treatment of Symptomatic Uterine Fibroids.

Uterine fibroids are benign tumors originating from smooth muscle tissue, constituting uterine muscle stroma. Uterine fibroids are the most common benign tumors found in women. In 20%-50% of women, fibroids are asymptomatic and do not require any treatment. The main symptoms of uterine fibroids are profuse menstrual bleeding, abnormal uterine bleeding, and pressure symptoms. Pressure symptoms can cause pelvic pain syndrome, urination disorders, and constipation. The treatment methods that are currently used include surgical treatment, pharmacological therapy, and minimally invasive procedures. The most commonly applied minimally invasive method is the embolization of uterine arteries. This procedure is currently a widely accepted method of treatment for symptomatic uterine fibroids and has been recognized as such by the National Institute for Health and Clinical Excellence in the guidelines for heavy menstrual bleeding. This is a complicated procedure and requires close cooperation between gynecologists and interventional radiologists. We present a protocol applicable to uterine artery embolization in the treatment of symptomatic uterine fibroids. The protocol is divided into five section. The first two section are intended for gynecologists and interventional radiologists, explaining how to qualify and prepare a patient for embolization in a step-by-step manner. Section three, which is directed at interventional radiologists, explains how embolization should be done. Section four is directed at gynecologists or hospital ward doctors who look after the patients after embolization. This section of the protocol offers a method for treating post-embolization pain using the Patient Controlled Analgesia (PCA) pump. Section five completes the procedure with an assessment of the effects and late complications of uterine artery embolization. All five section create a uniform protocol directed at clinicians, experts, and researchers new to the field.

Green urine sign after laparoscopic chromopertubation as an effect of severe contrast intravasation: a report of three cases.

Tubal diseases are responsible for 25% to 35% of female infertility. Laparoscopic chromopertubation is the gold standard for assessing tubal patency when female infertility is suspected. Intravasation is a complication of intrauterine procedures involving the passage of fluid filling the uterine cavity into the bloodstream through endometrial vessels (from the myometrial veins to the uterine venous plexuses). This complication has been described during hysterosalpingography and sonohysterosalpingography. We herein present a report of three cases in which severe intravasation occurred during laparoscopic chromopertubation using methylene blue as a contrast agent. The intravasation manifested as green urine (i.e., the "green urine sign"). The presence of methylene blue in the urine and blood was confirmed by laboratory tests. All three patients had risk factors for intravasation as described in the literature (unilateral or bilateral tubal obstruction, endometriosis, and previous intrauterine procedures for Mullerian duct anomalies and Asherman's syndrome). The green urine sign appeared a few hours after laparoscopic chromopertubation and spontaneously resolved after 24 hours. Cystoscopy was performed to rule out bladder injury. All three patients required only clinical observation.

The role of the "beret" sign and other markers in ultrasound diagnostic of the acrania-exencephaly-anencephaly sequence stages.

INTRODUCTION: Neural tube defects (NTDs) are a group of heterogeneous congenital anomalies of the central nervous system (CNS). Acrania is a non-NTD congenital disorder related to the CNS. It can transform into anencephaly through the acrania-exencephaly-anencephaly sequence (AEAS). In AEAS, the cerebral tissue is not protected and is gradually destroyed due to exposure to the harmful effect of amniotic fluid and mechanical injuries. These lead to exencephaly and then into anencephaly. In contrast to primary anencephaly (NTDs), this type of anencephaly authors suggests calling secondary anencephaly. OBJECTIVE: Analysis of the known prenatal ultrasonography (US) signs associated with AEAS. Simultaneously, the authors propose a new sign in the differentiation of acrania from exencephaly and anencephaly, called the "beret" sign. METHODS: It is a two-centre retrospective observational study. As part of the study, 4060 US scans were analyzed. RESULTS: In 10 cases, the absence of calvarium was diagnosed, allowing recognition of either AEAS stages or primary anencephaly. In 5 cases, cerebral structures were enclosed by an inertial rippled thin membrane, with a smooth outer contour. Between the described membrane and the brain structures, a thin anechoic space corresponding to cerebrospinal fluid was observed. This sign was defined as the "beret" sign. In these cases, acrania was diagnosed. In three cases calvarium was missing. The brain structures had an irregular appearance, did not wave and remained motionless. The outer contour was unequal as if divided into lobes. Amniotic fluid was anechoic. Exencephaly was diagnosed in these cases. In two cases calvarium, brain structures, and meninges were missing. The "frog eyes" sign and slightly echogenic amniotic fluid were visible. In this case, anencephaly was diagnosed. CONCLUSIONS: The "beret" sign seems to be a promising tool in the diagnosis of acrania. Furthermore, echogenicity of amniotic fluid could be useful during differentiation between primary and secondary anencephaly.

Effectiveness, complications and reproductive outcome of selective chemoembolization with methotrexate followed by suction curettage for caesarean scar pregnancy - A prospective observational study.

OBJECTIVE: Caesarean scar pregnancy (CSP) is a rare form of ectopic pregnancy implanted in a previous caesarean scar. Selective chemoembolization with methotrexate (SCEM) followed by suction curettage (SC) is one of the treatment options for CSP. The aim of the study was to assess the effectiveness, complications and reproductive outcome of SCEM followed by SC in the treatment of CSP. STUDY DESIGN: All cases of CSP treated with SCEM followed by SC between 2015 and 2018 were prospectively followed-up to assess short and long-term outcome. All patients hospitalized with the suspicion of CSP during the study period were included in the study. Gelatine sponge was used as embolic material to avoid permanent damage of the uterus and minimise the possible impact on fertility. Haemoglobin (Hb) and beta human chorionic gonadotropin (ß-hCG) levels, normalization of menstrual cycle, complications after the procedure and subsequent fertility were assessed. RESULTS: Twenty-two patients diagnosed with CSP underwent SCEM followed by SC. The procedure was effective in 20 cases (91%). In two cases additional SCEM was required before attempting SC due to persistent vascularity on ultrasound in one case and abnormal uterine bleeding in the second one. No complications were observed during the procedures, none of the patients required a hysterectomy. Follow-up ranged from 9 to 36 months. In short-term follow-up no significant complications occurred, only minor ailments such as uterine cramping and nausea were reported by 8 patients. In long-term follow-up 8 patients reported at least one complication, such as hypomenorrhea, amenorrhoea or were diagnosed with Asherman syndrome. Ten patients tried to conceive and 4 out of them achieved a pregnancy (all in less than 12 months) and delivered by caesarean sections between 35 and 39 weeks. One patient reported recurrent miscarriage. CONCLUSION: SCEM followed by SC appears to be an effective treatment option for CSP. The method seems to be safe in short-term follow-up. However, complications were observed in long-term follow-up. Therefore, patients should be informed about the risk of complications interfering with future fertility, such as intrauterine adhesions and/or amenorrhea.

The influence of nebivolol on the activity of BRL 37344 - the ß3-adrenergic receptor agonist, in the animal model of detrusor overactivity.

AIMS: The cardiotoxic effects of antimuscarinics constitute a significant restriction in their application in elderly people. Overactive bladder syndrome pharmacotherapy using compounds with cardioprotective properties would seem an ideal solution. The main goal of the study was to assess the impacts of nebivolol (NEB) on the activity of BRL 37344 - ß3-adrenergic receptor (ß3AR) agonist, in the animal model of detrusor overactivity. As both these substances can impact on the cardiovascular system, their effect on the parameters of this system and diuresis was also examined. METHODS: Retinyl acetate (RA; 0.75%) solution was used to induce detrusor overactivity in female Wistar rats. BRL and/or NEB were administered intra-arterially during cystometry in a single dose (2.5 or 5, 0.05 or 0.1 mg/kg, respectively). In addition, a 24 hours measurement of heart rate, blood pressure, and urine production was carried out. RESULTS: NEB (0.05 mg/kg) and BRL (2.5 mg/kg) monotherapy proved to have no influence on the cystometric parameters of animals with RA-induced detrusor overactivity. NEB at 0.1 mg/kg resulted in a drop in the detrusor overactivity index, similarly to BRL at 5 mg/kg. Coadministration of NEB and BRL, both at ineffective doses, decreased the detrusor overactivity index and ameliorated the nonvoiding contractions. ß3AR stimulation proved to induce tachycardia and hypertension. NEB at 0.05 mg/kg proved to ameliorate detrusor overactivity and have preventive properties against adverse cardiovascular effects of the ß3AR agonist. CONCLUSIONS: The combined application of the ß3AR agonist and NEB may improve detrusor overactivity without affecting the heart rate, blood pressure, and urine production.

Is it necessary to correct a caesarean scar defect before a subsequent pregnancy? A report of three cases.

Rates of caesarean section have increased over recent years and so too have associated complications, one of which is a caesarean scar defect (CSD). The defect may cause gynaecological symptoms, such as menometrorrhagia, infertility, chronic abdominal/pelvic pain or it may be asymptomatic. The presence of CSD may lead to obstetrical sequalae such as preterm delivery, uterine rupture, caesarean scar pregnancy or abnormal placenta implantation. Three cases of CSD are described here. In one case, surgical correction of the CSD was performed before a subsequent pregnancy with an uncomplicated obstetric outcome. In the other two cases, surgical correction of the CSD was not performed and the pregnancies were complicated by caesarean scar dehiscence and caesarean scar pregnancy. We suggest that women with a CSD may benefit from surgical correction of the defect before becoming pregnant to reduce the likelihood of serious complications.

Blebbistatin, a Myosin II Inhibitor, Exerts Antidepressant-Like Activity and Suppresses Detrusor Overactivity in an Animal Model of Depression Coexisting with Overactive Bladder.

Overactive bladder (OAB) coexists with depression in women. Here, we assessed the effects of a 1-week treatment with blebbistatin, a myosin II inhibitor, on changes in behavior and detrusor overactivity (DO) symptoms induced by a 6-week administration of 13-cis-retinoic acid (13-cis-RA), with the aid of the forced swim test (FST), spontaneous locomotor activity test, and in vivo cystometric investigations in female Wistar rats. 13-cis-RA-induced depressive-like behavior and DO symptoms were associated with increased corticotropin-releasing factor (CRF) level in the plasma, prefrontal cortex (PFC), hippocampus (Hp), Barrington's nucleus (BN), and urinary bladder. Moreover, 13-cis-RA decreased brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) levels in plasma, PFC, Hp, and BN, while it increased BDNF and NGF levels in urinary bladder. Blebbistatin exerted antidepressant-like effect and attenuated changes in the cystometric parameters as well as the central and peripheral levels of CRF, BDNF, and NGF that were induced by 13-cis-RA, while it did not affect urine production, mean, systolic or diastolic blood pressure, or heart rate. The results point to blebbistatin as a potential treatment option for OAB coexisting with depression.

The role of ultrasonography in methotrexate therapy for ectopic pregnancy.

Medical management of ectopic pregnancy with methotrexate, an antimetabolite of folic acid, is an important alternative to surgical treatment, as it ensures a similar outcome whilst being far less invasive. Ultrasound evaluation does not only facilitate an accurate diagnosis, but also helps to select patients most likely to benefit from methotrexate treatment, as opposed to those with a high likelihood of failure of medical management, who are thus eligible for primary surgical treatment. Ultrasound also allows to monitor the outcome of methotrexate therapy. This study is a review of literature regarding the management of ectopic pregnancy with methotrexate. Such ultrasound findings as the size of the ectopic mass, presence of fetal heart rate and free fluid have been confirmed as effective eligibility criteria for therapy with methotrexate. In the future, possibly also endometrial stripe thickness and the vascularity of the ectopic mass may be considered predictive of successful methotrexate therapy. The initial increase in size of the ectopic mass following methotrexate therapy confirms its effectiveness, and should not prompt concern.

Ascites Index - an attempt to objectify the assessment of ascites.

INTRODUCTION: Ascites is observed in cancer patients as well as in other non-neoplastic processes. In some patients, it may cause severe symptoms that can become directly life-threatening. The assessment of the degree of ascites seems useful in the determination of treatment effects as well as in the monitoring of fluid accumulation and early planning of decompression procedures. AIM: Determination of the clinical usefulness of a quantitative method of determining the degree of ascites, so-called Ascites Index. MATERIAL AND METHODS: The Ascites Index is an ultrasonographic way of assessing the grade of ascites. The examination result is an index which is analogous to the amniotic fluid index determined in pregnant patients. The Ascites Index was determined in patients with ascites in the course of stage III-IV ovarian carcinoma (7 patients) and ovarian hyperstimulation syndrome (12 patients). RESULTS: The patients with ovarian hyperstimulation syndrome required decompressive paracentesis at the median Ascites Index above 290 mm (range: 216-386 mm). In the patients with ovarian carcinoma, the median value of the Ascites Index at which paracentesis was required was 310 mm (range: 273-389 mm). To avoid complications associated with excessive protein loss, 2000 mL of fluid was evacuated at a single occasion. Following the procedure, the median value of the Ascites Index was 129 mm (range: 121-145 mm) in the patients with ovarian hyperstimulation syndrome and 146 cm (119-220 mm) in cancer patients. CONCLUSIONS: The proposed index is simple and rapid to determine. It makes evaluation of the degree of ascites considerably easier. Moreover, it only minimally burdens patients and enables assessment of the effect of decompression or treatment. It seems that this method might be useful also in the assessment of ascites caused by other factors, but this requires further clinical studies.

A viewpoint on rational and irrational fixed-drug combinations.

INTRODUCTION: Considering that there are around 30% of patients with epilepsy resistant to monotherapy, the use of synergistic combinations of antiepileptic drugs is of particular importance. This review shows most beneficial as well as irrational combined treatments both from an experimental and clinical point of view. Areas covered: Preferably, experimental data derived from studies evaluating synergy, additivity, or antagonism by relevant methods, in terms of anticonvulsant or neurotoxic effects and pharmacokinetic data have been considered. Although there have been no randomized clinical trials on this issue, the clinical data have been analyzed from studies on considerable numbers of patients. Case-report studies have been not considered. Expert commentary: The experimental data provide a strong support that co-administration of lamotrigine with carbamazepine is negative, considering the anticonvulsant and neurotoxic effects. Clinical reports do not entirely support this conclusion. Other experimentally documented negative combinations comprise lamotrigine+ oxcarbazepine and oxcarbazepine+ phenytoin. From the experimental and clinical point of view, a combination of lamotrigine+ valproate may deserve recommendation. Other most positive experimental and clinical combinations include carbamazepine+valproate, phenytoin+phenobarbital, carbamazepine+gabapentin, carbamazepine+topiramate, levetiracetam+valproate, levetiracetam+carbamazepine. Certainly, experimental data have some limitations (non-epileptic animals, acute administration of antiepileptic drugs) so all experimental recommendations need a careful clinical evaluation.

Comparison of the influence of three fibroid treatment options: supracervical hysterectomy, ulipristal acetate and uterine artery embolization on ovarian reserve - an observational study.

BACKGROUND: To assess and compare the influence of three fibroid treatment options: supracervical hysterectomy, ulipristal acetate and uterine artery embolization on ovarian reserve. METHODS: Prospective, observational, open-label study performed at the 3rd Chair and Department of Gynecology of the Medical University of Lublin, Poland. Premenopausal Caucasian women with symptomatic uterine fibroids were recruited into 3 groupspatients qualified for supracervical hysterectomies; patients qualified for preoperative ulipristal acetate (UPA) treatment scheduled for supracervical hysterectomies or myomectomies; patients qualified for uterine artery embolization (UAE). The following markers of ovarian reserve were investigated: antral follicle count (AFC), anti-Mullerian hormone (AMH), inhibin B (INHB), follicle stimulating hormone (FSH) and estradiol (E2). These markers were assessed before and 3 months after supracervical hysterectomies, before and 3 months after UAEs, and before and after 3 months of UPA treatment, before the scheduled surgeries. Baseline characteristics (age, parity, dominant fibroid volume, hemoglobin level, BMI, as well as AFC, AMH, INHB, FSH and E2) were compared between the study groups by Kruskall-Wallis ANOVA. Pre- and post-interventional values of AFC, AMH, INHB, FSH and E2 in the studied groups were compared with the Wilcoxon matched pairs test. RESULTS: Twenty-six, 27 and 30 patients were included in the final analysis in the supracervical hysterectomy, UPA and UAE groups, respectively. Three months after supracervical hysterectomy INHB and E2 significantly decreased, while AFC, AMH and FSH remained unchanged. After 3 months of UPA treatment the values of all the assessed markers of ovarian reserve were not significantly different in comparison to baseline. Conversely, three months after UAE the values of AFC, AMH, INHB, and E2 were significantly decreased, while FSH was significantly increased. CONCLUSIONS: Of the compared fibroid treatment methods UAE seems to have the greatest impact on ovarian function and should not be offered to patients concerned about their ovarian function. Supracervical hysterectomy did not affect the most accurate markers of ovarian reserve, and therefore appears to be safe in terms of ovarian function. UPA did not change any of the studied markers of ovarian reserve and seems a reasonable option when ovarian function is concerned.

Ascites Index - a novel technique to evaluate ascites in ovarian hyperstimulation syndrome: a concept-proof study.

OBJECTIVES: Controlled ovarian hyperstimulation is an important step in infertility treatment. In some cases, however, ovar-ian hyperstimulation syndrome (OHSS) can occur. In its severe forms, ascites is likely to develop, associated with dyspnea. The aim of this study was to explore the usefulness of Ascites Index (AsI), a new tool for quantitative determination of ascites in patients with OHSS, to obtain data for planning further trials. MATERIAL AND METHODS: Twelve patients with OHSS and ascites were included in the study. All patients were admitted to the hospital because of abdominal pain and dyspnea due to increasing ascites. Ultrasound measurements of ascites extent were performed in four external quadrants of the abdomen. Pockets of free fluid were measured. The obtained values were totaled, forming the Ascites Index (AsI), similarly to the amniotic fluid index. Because of dyspnea, paracentesis was performed in all cases. RESULTS: Median AsI at which patients reported dyspnea was 29.0 cm (range 21.6-38.6 cm). At AsI values less than 21.6 cm, no dyspnea was observed in any of the 12 studied patients. To avoid complications, 2000 mL of ascitic fluid was collected in each patient. After paracentesis, range of AsI decreased to 12.1-14.5 cm. CONCLUSIONS: The proposed AsI seems to be a promising tool for estimating and monitoring the ascites extent in OHSS. It can be estimated using basic ultrasound equipment. AsI requires further studies for standardization and transferability to other causes of ascites.

Extensive postpartum urinary retention successfully treated with clean intermittent catheterization.

We present a case of extensive urine retention after vaginal delivery. Postpartum urinary retention occurs in 0.7 to 0.9% of vaginal deliveries. In the literature, mediolateral episiotomy, epidural analgesia, perineal lacerations, macrosomic birth and prolonged 2nd stage of labor are suggested as risk factors for postpartum urine retention.

Use of a levonorgestrel-releasing intrauterine device for menorrhagia treatment during adjuvant therapy of adrenocortical carcinoma with mitotane.

Adrenocortical carcinoma is a rare tumour with high malignancy and poor prognosis. This tumour is rarely diagnosed in the reproductive age. Complete surgical resection is the only curative treatment for adrenal cancer in all stages. After surgery adjuvant chemotherapy is required. Mitotane is the most important drug in adrenal cancer chemotherapy. Mitotane's mode of action is not entirely explained. Animal studies have shown that the substance exerts a direct cytotoxic effect on the cells of the adrenal cortex. This activity is selective, progressive and affects only the zona reticularis and fasciculata of the adrenal cortex. Mitotane inhibits cortisol synthesis by disrupting the chain of cholesterol. It has been suggested, that mitotane also affects the peripheral metabolism of steroids, especially of transcortin (CBG). This results in an increase of CBG blood concentration and a reduction of the amount of free hormones.

Primary ovarian Burkitt's lymphoma: a rare oncological problem in gynaecology: a review of literature.

PURPOSE: This review presents the information about epidemiology, clinical manifestation, diagnosis and treatment of primary ovarian Burkitt's lymphoma (BL), including a literature search of available BL cases. The purpose of this review is to draw clinicians' attention to the possibility of ovarian BL occurrence, which may be important in the differential diagnosis of ovarian tumours. METHODS: PubMed and Web of Science databases were searched using the keywords ''Burkitt's'', ''Lymphoma'', ''Ovarian'', ''Primary'', ''Burkitt's lymphoma''. Only cases with histopathologically confirmed diagnosis of primary ovarian BL were included in this review. RESULTS: Fifty articles, reporting cases with an ovarian manifestation of primary non-Hodgkin's lymphoma, were found. Twenty-one cases with a histopathologically confirmed BL were evaluated to compare various manifestations, treatment and prognosis in ovarian BL. CONCLUSIONS: Primary ovarian BL is a rare condition, included in the entity of non-Hodgkin lymphoma. The tumour can occur uni- or bilaterally in the ovaries with major symptoms such as abdominal pain or a large abdominal mass. Differential diagnosis, based on imaging features and pathological examination of the specimens, is essential for further treatment due to various aetiology of ovarian tumours. Although most of the patients suffering from ovarian BL underwent surgery after the ovarian tumour had been detected, surgical treatment is not the treatment of choice in patients with ovarian lymphoma. The mainstay of therapy is chemotherapy without further surgery. The prognosis is better if the chemotherapy protocol is more aggressive and followed by prophylactic central nervous system chemotherapy. Nowadays, multiagent protocols are administered, which improves the survival rate.

Secondary dysmenorrhea due to a rudimentary, non-communicating functional uterine horn.

Unicornuate uterus with a rudimentary horn is a rare congenital Müllerian anomaly, which may lead to many obstetrical and gynaecological complications. This pathology occurs in approximately 1/100 000 women. A rudimentary horn forms due to insufficient development of the Müllerian duct. The diagnosis of this anomaly is usually delayed, as it remains asymptomatic until adolescence and its main symptom is dysmenorrhea.