Piotr Czuczwar

Sedative and anticonvulsant drugs suppress postnatal neurogenesis

Sedative and anticonvulsant drugs, which inhibit N‐methyl‐D‐aspartate receptor–mediated excitation or enhance GABA‐mediated action, may cause apoptotic neurodegeneration in the developing mammalian brain. Here we explored whether such agents influence early postnatal neurogenesis.

Pharmacodynamic and pharmacokinetic characterization of interactions between levetiracetam and numerous antiepileptic drugs in the mouse maximal electroshock seizure model: an isobolographic analysis.

Summary:  Purpose: Approximately 30% of patients with epilepsy do not experience satisfactory seizure control with antiepileptic drug (AED) monotherapy and often require polytherapy. The potential usefulness of AED combinations, in terms of efficacy and adverse effects, is therefore of major importance. The present study sought to identify potentially useful AED combinations with levetiracetam (LEV)

Levetiracetam selectively potentiates the acute neurotoxic effects of topiramate and carbamazepine in the rotarod test in mice.

The effect of levetiracetam (LEV) on the acute neurotoxic profiles of various antiepileptic drugs (carbamazepine [CBZ], phenytoin [PHT], phenobarbital [PB], valproate [VPA], lamotrigine [LTG], topiramate [TPM], oxcarbazepine [OXC], and felbamate [FBM]) was evaluated in the rotarod test, allowing the determination of median toxic doses (TD50 values) with respect to impairment of motor coordination in mice. The TD50 of LEV administered singly was 1601 mg/kg. Whilst LEV at 150 mg/kg, being its TID50 (a dose increasing the electroconvulsive threshold by 50%), was without effect with regards to motor coordination impairment associated with PHT, PB, VPA, LTG, OXC, and FBM, it significantly enhanced that associated with CBZ and TPM co-administration. Thus LEV (150 mg/kg) significantly decreased the TD50 of CBZ from 53.6 to 37.3 mg/kg (P<0.01) and that of TPM from 423 to 246 mg/kg (P<0.01). In addition LEV (75 mg/kg) significantly decreased the TD50 of TPM from 423 to 278 (P<0.01). That concurrent measurement of total brain LEV, CBZ, and TPM concentrations showed that concentrations were not significantly different when AEDs were administered singly compared to when they were administered in combination would suggest that there is no pharmacokinetic interaction between these AEDs. Thus, the observed potentialization of the acute neurotoxic effects of CBZ and TPM by LEV is the consequence of a pharmacodynamic interaction. These data support both experimental and clinical published data advocating that LEV may interact with some AEDs by pharmacodynamic mechanisms.

Retigabine: the newer potential antiepileptic drug

Retigabine represents an antiepileptic drug possessing a completely different mechanism of action when compared to the existing classical and newer antiepileptic drugs. In the therapeutic range, retigabine enhances potassium currents, very likely via destabilization of a closed conformation or stabilization of the open conformation of the potassium Kv7.2-7.3 channels. There are also data indicating that this drug may be a GABA enhancer. Kainate-induced status epilepticus in rats resulted in massive apoptosis in the pyriform cortex and hippocampal area - retigabine inhibited neurodegeneration only in the former brain structure. The metabolism of retigabine has nothing to do with cytochrome P450 enzymes and the drug undergoes glucuronidation and acetylation. Randomized, placebo-controlled multicenter studies have shown that retigabine produced a considerable improvement as an add-on drug in patients with partial drug-resistant epilepsy. The most prominent adverse effects due to retigabine combined with the existing antiepileptic treatment were dizziness, somnolence and fatigue. The preclinical data indicate that this antiepileptic drug may possibly be applied in patients with neuropathic pain and affective disorders. Initial clinical data suggest that retigabine may be also effective in Alzheimers disease or stroke.

Influence of ulipristal acetate therapy compared with uterine artery embolization on fibroid volume and vascularity indices assessed by three‐dimensional ultrasound: prospective observational study

To compare the effects of two alternative treatment options for uterine fibroids, ulipristal acetate (UPA) and uterine artery embolization (UAE), on fibroid volume and vascularity at 3‐month follow‐up.

Infertility in the light of new scientific reports – focus on male factor

Epidemiological data indicate that infertility is a problem of global proportions, affecting one- fifth of couples trying to conceive worldwide (60-80 mln). According to the trends observed, the problem is predicted to increase by another two million cases annually. In Poland, infertility-related issues are found in about 19% of couples, including 4% with infertility and 15% with limited fertility. Inability to conceive occurs equally in men and women (50%), irrespective of the direct cause. Although it is generally thought that reproductive issues concern women, infertility affects men and women equally. This study is an attempted to systematize knowledge about the role of the male factor in infertility, particularly current knowledge concerning the environmental factors of infertility. For this purpose, the Medline and CINAHL databases and the Cochrane Library was searched for articles published in English during the last 10 years, using the following keywords: infertility, male factor, semen examination and environmental factor of infertility.

Delayed Diagnosis of Herlyn-Werner-Wunderlich Syndrome due to Microperforation and Pyocolpos in Obstructed Vaginal Canal

BACKGROUND To present a rare anomaly consisting of uterus didelphys, longitudinal vaginal septum, obstructed hemivagina with pyocolpos, fistula to the open vaginal canal, and ipsilateral renal agenesis, referred as Herlyn-Werner-Wunderlich syndrome (HWWS). CASE A 14-year-old girl with recurring purulent vaginal discharge lasting for a few months. Preoperative examination revealed one vaginal canal with one cervical opening on the right side. There was a fistula leading from the obstructed vaginal canal to the left vagina. Intravaginal ultrasound examination demonstrated a longitudinal vaginal septum and a closed pyocolpos on the right side. The longitudinal vaginal septum was excised by way of electrocauterization under direct vision. CONCLUSION HWWS should be considered in the differential diagnosis in patients with uterus didelphys and unusual symptoms such as pyocolpos and vaginal discharge.

Predicting the results of uterine artery embolization: correlation between initial intramural fibroid volume and percentage volume decrease

Introduction and objective Uterine artery embolization (UAE) is a minimally invasive treatment option for symptomatic fibroids. Long-term follow-up studies have shown that at five-year follow-up after UAE, up to 30% of patients required a hysterectomy. Therefore, it seems of utmost importance to identify patients, who are unlikely to benefit from UAE. It has been postulated that the percentage volume reduction of fibroids may predict long-term UAE outcome. The results of available studies are equivocal, therefore it seemed of interest to investigate the correlation between the preinterventional intramural fibroid volume and imaging outcome of UAE in premenopausal patients. Material and methods Uterine artery embolization was performed in 65 premenopausal patients with symptomatic, intramural fibroids. Dominant fibroid volume was assessed using an integrated VOCAL (Virtual Organ Computer-aided AnaLysis) imaging program at baseline and 3 months after UAE. The percentage reduction of fibroid volume was calculated. The association between preinterventional fibroid volumes and percentage volume reductions was determined with the Spearman rank correlation test. Results Before UAE, the median dominant fibroid volume was 101 cm3 (range 23.6-610). At three-month follow-up the median dominant leiomyoma volume decreased to 50.4 cm3 (range 6.9-193.9). Median percentage reduction of fibroid volume three months after UAE was calculated at 50.1% (range 2.7-93.5). The Spearman correlation test between the preinterventional dominant fibroid volume and percentage volume reduction showed a statistically significant, positive correlation (R = 0.33; p = 0.006). Conclusions The percentage volume reduction of intramural leiomyomas after UAE seems to be more pronounced in the case of larger tumors.

Embolisation in the Therapy of Post-Partum Haemorrhage in a Patientwith a Massive Myoma

Study background: The world prevalence of post-partum haemorrhage is approx. 10.5% of pregnancies, and it is the leading mortality cause among young women, accounting for approx. 25% of fatalities. Post-partum haemorrhage is defined as over 500 ml blood loss from genitals, occurring within the first 24 hours post partum. The presented case is an example of efficacy of the embolisation procedure in the management of post-partum haemorrhage. A 29-y.o. female patient was referred to the hospital in her third pregnancy. Because of the presence of a massive myoma the patient was qualified for delivery by Caesarean section. The child was delivered. The uterine muscle was sutured. Haemostasis control - no signs of active bleeding. Three hours after the Caesarean section a massive postpartum haemorrhage developed. Oxytocin and Methylergometrin were administered intravenously, and Mizoprostol per rectum. The bleeding from the uterine cavity was still massive, and a decision was made on embolisation of uterine arteries. Methods: The procedure was performed with access via the right femoral artery, under local anaesthesia. A selective injection of a contrast medium to the left uterine artery was performed, which allowed visualisation of the uterine vascular bed with the myoma, as well as of the site of the active, massive bleeding. First the left uterine artery was embolised with particles, in order to close the vascular bed of the myoma. Then, a part of the vessel supplying the uterine muscle with the bleeding site, was closed with Spongostan gel. Results: Control angiography indicated a correctly closed left uterine artery, with no filling of the uterine vascular bed. No other sites of bleeding were detected. Conclusion: The selective embolisation of vessels in course of a postpartum haemorrhage in that case was a safe, minimally invasive and highly effective therapeutic method, that ensures an option of further pregnancies.

P31.01: Ascites index—a new method of ultrasound evaluation of ascites volume in patients with ovarian cancer

Objectives: Ascites is often observed in malignant diseases, and is then associated with a poor prognosis. In 30–54% cases of ascites ovarian cancer is the primary tumor. Effective palliation of symptoms caused by the pressure of ascites is difficult to achieve. Assessment of the volume of ascites is necessary in monitoring the progress of the disease and in selecting appropriate methods of treatment. The aim of this study was to introduce Ascites Index (AsI), a simple to use ultrasound method of evaluating the volume of ascites. Methods: Six patients with ovarian cancer and ascites were included in the study. All patients were admitted to the hospital because of respiratory dysfunction (dyspnea) due to increasing ascites. Ultrasound measurements of the volume of ascites were performed in the external quadrants of the abdomen – in the vicinity of the liver, spleen and bilaterally above the inguinal ligament. Pockets of free fluid were measured in millimeters, perpendicularly to the tangents of each quadrant of the abdomen. The obtained values were totalled, creating the Ascites Index (AsI), similary to the amniotic fluid index. Abdominal puncture was performed in 4 cases, and exploratory laparotomy in 2 cases. AsI values acquired before and after these procedures were subsequently compared. Results: Initial AsI values ranged from 196 to 316 mm (mean 233 mm, SD 47.0). To avoid complications a maximum of 2000 ml of ascitic fluid was collected. After abdominal puncture AsI values were decreased to 89–183 mm (mean 129 mm; SD 42.5). During exploratory laparotomy 4500–5000 ml of fluid was obtained, and after the procedure the index was decreased to 6–19 mm (mean 12.5 mm; SD 9.2). Conclusions: The proposed Ascites Index seems to by a promising tool in estimating ascites volume. It is simple to implement and may be estimated using basic ultrasound equipment even in outpatient clinic. AsI may be useful in monitoring ascites, predicting dyspnea and assessing the effect of abdominal puncture.