Efektywność leczenia zespołu bólowego miednicy mniejszej metodą neurektomii przedkrzyżowej u pacjentek z i bez endometriozy

Abstract Objective: Presacral neurectomy (PSN) is used in treatment of central chronic pelvic pain (CPP); however, the confounding effect of concomitant resection of endometriosis remains uncertain. This study was undertaken to evaluate and compare the effectiveness of presacral neurectomy (PSN) in the presence and absence of endometriosis. Material and Methods: Twenty-three women with midline CPP (age 30.3+/-7.9, range 21-46) unresponsive to medical therapy were recruited to the study. Endometriosis was absent in seven and present in sixteen subjects. Laparoscopic PSN using a harmonic scalpel was performed in all subjects; simultaneous excision of endometriotic lesions was also carried out in subjects with endometriosis. Intensity of dysmenorrhoea and pelvic pain was measured by visual analogue pain scale (VAPS) at 3 and 12 months postoperatively. Results: Dysmenorrhoea decreased at 3 months by 75% (P=0.018) in those without endometriosis and by 78% (P=0.001) in those with endometriosis. At 12-months, dysmenorrhea increased in women with endometriosis (P=0.008), but not in those without endometriosis. Pelvic pain not related to menses decreased by 67% (P=0.0007) and by 87% (P=0.028), respectively, in women with and without endometriosis. Dyspareunia, declined dramatically at 3 and 12 months to a median score of 0 (the majority of subjects had no discomfort; PStreszczenie Cel pracy: Neurektomia przedkrzyżowa jest stosowana w leczeniu zespołu bólowego miednicy mniejszej, jakkolwiek sumaryczny efekt jednoczasowo przeprowadzonej resekcji ognisk endometriozy pozostaje niejasny. Prezentowana praca ma na celu porównanie skuteczności laparoskopowej neurektomii przedkrzyżowej w przypadku obecności endometriozy, oraz u chorych, u których ta choroba nie występuje. Materiał i metody: Badaniem objęto dwadzieścia trzy kobiety z centralnie zlokalizowanym przewlekłym bólem miednicy mniejszej (wiek 30,3+/-7,9; 21-46 lat), nieodpowiadającym na leczenie farmakologiczne. Endometriozę stwierdzono u 16 pacjentek. W badanej grupie wykonano laparoskopową neurektomię przedkrzyżową z zastosowaniem skalpela harmonicznego, uzupełnioną o wycięcie ognisk endometriozy w 16 w/w przypadkach. Nasilenie bólu towarzyszącego krwawieniu miesiączkowemu oraz bólu niezwiązanego z krwawieniem oceniano na podstawie wzrokowej skali bólu (VAPS) przed zabiegiem oraz po 3 i 12 miesiącach po operacji. Bolesność stosunków płciowych oceniono z zastosowaniem czterostopniowej skali. Wyniki: Po 3 miesiącach od operacji intensywność bólu związanego z krwawieniem miesiączkowym zmniejszyła się znacząco w obu grupach pacjentek (u chorych bez endometriozy o 75% (P=0,018), a w grupie z endometriozą o 78% (P=0,001). Po 12 miesiącach zaobserwowano wzrost intensywności odczuwanego bólu u kobiet z endometriozą (P=0,008), natomiast u pacjentek bez endometriozy poprawa była na niezmienionym poziomie. Odczuwalność bólu w miednicy mniejszej niezwiązanego z krwawieniem miesiączkowym zmniejszyła się na skutek operacji o 67% (P=0,0007) i o 87% (P=0,028) odpowiednio w grupie z endometriozą i bez endometriozy. Bolesność stosunków płciowych zmniejszyła się istotnie 3 miesiące po operacji i efekt utrzymywał się nadal po 12 miesiącach (większość pacjentek nie podawała żadnego dyskomfortu,

Useful pharmacodynamic endpoints in children: selection, measurement, and next steps.

Pharmacodynamic (PD) endpoints are essential for establishing the benefit-to-risk ratio for therapeutic interventions in children and neonates. This article discusses the selection of an appropriate measure of response, the PD endpoint, which is a critical methodological step in designing pediatric efficacy and safety studies. We provide an overview of existing guidance on the choice of PD endpoints in pediatric clinical research. We identified several considerations relevant to the selection and measurement of PD endpoints in pediatric clinical trials, including the use of biomarkers, modeling, compliance, scoring systems, and validated measurement tools. To be useful, PD endpoints in children need to be clinically relevant, responsive to both treatment and/or disease progression, reproducible, and reliable. In most pediatric disease areas, this requires significant validation efforts. We propose a minimal set of criteria for useful PD endpoint selection and measurement. We conclude that, given the current heterogeneity of pediatric PD endpoint definitions and measurements, both across and within defined disease areas, there is an acute need for internationally agreed, validated, and condition-specific pediatric PD endpoints that consider the needs of all stakeholders, including healthcare providers, policy makers, patients, and families.Pediatric Research advance online publication, 11 April 2018; doi:10.1038/pr.2018.38

Ovarian cancer

Ovarian cancer is not a single disease and can be subdivided into at least five different histological subtypes that have different identifiable risk factors, cells of origin, molecular compositions, clinical features and treatments. Ovarian cancer is a global problem, is typically diagnosed at a late stage and has no effective screening strategy. Standard treatments for newly diagnosed cancer consist of cytoreductive surgery and platinum-based chemotherapy. In recurrent cancer, chemotherapy, anti-angiogenic agents and poly(ADP-ribose) polymerase inhibitors are used, and immunological therapies are currently being tested. High-grade serous carcinoma (HGSC) is the most commonly diagnosed form of ovarian cancer and at diagnosis is typically very responsive to platinum-based chemotherapy. However, in addition to the other histologies, HGSCs frequently relapse and become increasingly resistant to chemotherapy. Consequently, understanding the mechanisms underlying platinum resistance and finding ways to overcome them are active areas of study in ovarian cancer. Substantial progress has been made in identifying genes that are associated with a high risk of ovarian cancer (such as BRCA1 and BRCA2), as well as a precursor lesion of HGSC called serous tubal intraepithelial carcinoma, which holds promise for identifying individuals at high risk of developing the disease and for developing prevention strategies

Lipophilic statins inhibit growth and reduce invasiveness of human endometrial stromal cells

PURPOSE:To compare effects of lipid-soluble statins (simvastatin, lovastatin, atorvastatin) and water-soluble statin (pravastatin) on growth and invasiveness of human endometrial stromal (HES) cells. METHODS:Endometrial biopsies were collected during the proliferative phase from five volunteers. HES cells were isolated and cultured in the absence or in the presence of simvastatin, lovastatin, atorvastatin, and pravastatin. Effects of statins on DNA synthesis, cell viability, activity of caspases 3/7 and invasiveness were evaluated. RESULTS:The proliferation of HES cells was significantly decreased by simvastatin (by 47-89%), lovastatin (by 46-78%), and atorvastatin (by 21-48%) in a concentration-dependent manner. Activity of executioner caspases 3/7 was significantly increased by simvastatin (by 10-25%), lovastatin (by 19%) and atorvastatin (by 7-10%) in a concentration-dependent manner. The greatest effects were observed in response to simvastatin. Accounting for the effects of statins on cell number, the invasiveness of HES cells was significantly decreased in cells treated with simvastatin (by 49%), lovastatin (by 54%), and atorvastatin (by 53%). Pravastatin had little or no effects on any of the tested endpoints. CONCLUSIONS:Present findings demonstrate that only lipid-soluble among tested statins were effective in inhibition of growth and invasiveness of HES cells. These findings may have clinical relevance in treatment of endometriosis

Comparison of Effects of Different Statins on Growth and Steroidogenesis of Rat Ovarian Theca-Interstitial Cells1

Statins are competitive inhibitors of 3-hydroxy-3-methyl-glutaryl-CoA reductase, the rate-limiting enzyme of the cellular production of cholesterol and other products of the mevalonate pathway. Statins exert hepatic and extrahepatic effects, modulating the function of various tissues and organs, including ovaries. Previously, we have demonstrated that simvastatin inhibited cellular proliferation and reduced androgen production by ovarian theca-interstitial cells. The above actions are of translational relevance to the most common endocrine disorder among women in reproductive age: polycystic ovary syndrome. However, different statins may have distinctly different profiles of effects on cholesterol and androgens. The present study was designed to compare the effects of several statins on growth and steroidogenesis of rat theca-interstitial cells. The cells were incubated in the absence (control) or in the presence of simvastatin, lovastatin, atorvastatin, or pravastatin. Assessment of effects of statins on cell growth was carried out by evaluation of DNA synthesis and by estimation of the number of viable cells. Effects on steroidogenesis were evaluated by quantification of steroid production and expression of mRNA for the key enzyme regulating androgen production: Cyp17a1. Among tested statins, simvastatin exerted the greatest inhibitory effects on all tested parameters. The rank order of the effects of the tested statins is as follows: simvastatin > lovastatin > atorvastatin ≥ pravastatin. While the lipophilicity is likely to play a major role in determining the ability of statins to act on nonhepatic cells, other factors unique to individual cell types are also likely to be relevant

Spatial root distribution of mature apple trees under drip irrigation system

The study was undertaken in order to quantify the effect of 12-year irrigation by drip emitters placed on one side of the tree trunk on the rooting pattern of Gloster apple trees (Malus domestica Borkh) grafted on M26 rootstock under the conditions of south-west Poland. The orchard was established in 1994 and since 1995 was drip irrigated under three treatments: V0 - without irrigation (control), V1 - intensive irrigation, and V2 - economical irrigation. In March 2007, after 12 years of irrigation, a profile trench observation method was used to map the number and the location of root distribution in clay loam (Luvisol) soil. The root system architecture was largely affected by irrigation. In case of the trees irrigated intensively (V1), the study showed asymmetry in the distribution of roots of diameterApple tree Drip irrigation Yield Spatial root distribution