Altered dynamics of lipid metabolism in muscle cells from patients with idiopathic inflammatory myopathy is ameliorated by 6 months of training.

KEY POINTS: Regular exercise improves muscle functional capacity and clinical state of patients with idiopathic inflammatory myopathy (IIM). In our study, we used an in vitro model of human primary muscle cell cultures, derived from IIM patients before and after a 6-month intensive supervised training intervention to assess the impact of disease and exercise on lipid metabolism dynamics. We provide evidence that muscle cells from IIM patients display altered dynamics of lipid metabolism and impaired adaptive response to saturated fatty acid load compared to healthy controls. A 6-month intensive supervised exercise training intervention in patients with IIM mitigated disease effects in their cultured muscle cells, improving or normalizing their capacity to handle lipids. These findings highlight the putative role of intrinsic metabolic defects of skeletal muscle in the pathogenesis of IIM and the positive impact of exercise, maintained in vitro by yet unknown epigenetic mechanisms. ABSTRACT: Exercise improves skeletal muscle function, clinical state and quality of life in patients with idiopathic inflammatory myopathy (IIM). Our aim was to identify disease-related metabolic perturbations and the impact of exercise in skeletal muscle cells of IIM patients. Patients underwent a 6-month intensive supervised training intervention. Muscle function, anthropometric and metabolic parameters were examined and muscle cell cultures were established (m. vastus lateralis; Bergström needle biopsy) before and after training from patients and sedentary age/sex/body mass index-matched controls. [14 C]Palmitate was used to determine fat oxidation and lipid synthesis (thin layer chromatography). Cells were exposed to a chronic (3 days) and acute (3 h) metabolic challenge (the saturated fatty acid palmitate, 100 µm). Reduced oxidative (intermediate metabolites, -49%, P = 0.034) and non-oxidative (diglycerides, -38%, P = 0.013) lipid metabolism was identified in palmitate-treated muscle cells from IIM patients compared to controls. Three days of palmitate exposure elicited distinct regulation of oxidative phosphorylation (OxPHOS) complex IV and complex V/ATP synthase (P = 0.012/0.005) and adipose triglyceride lipase in patients compared to controls (P = 0.045) (immunoblotting). Importantly, 6 months of training in IIM patients improved lipid metabolism (CO2 , P = 0.010; intermediate metabolites, P = 0.041) and activation of AMP kinase (P = 0.007), and nearly normalized palmitate-induced changes in OxPHOS proteins in myotubes from IIM patients, in parallel with improvements of patients' clinical state. Myotubes from IIM patients displayed altered dynamics of lipid metabolism and impaired response to metabolic challenge with saturated fatty acid. Our observations suggest that metabolic defects intrinsic to skeletal muscle could represent non-immune pathomechanisms, which can contribute to muscle weakness in IIM. A 6-month training intervention mitigated disease effects in muscle cells in vitro, indicating the existence of epigenetic regulatory mechanisms.

How Imaging Can Assist with Diagnosis and Monitoring of Disease in Myositis.

PURPOSE OF REVIEW: To summarize recent findings and progression in the field of imaging of inflammatory myopathies. The most commonly used method is magnetic resonance imaging, and the article focuses on this technique, but covers also several other less frequently used or emerging methods. RECENT FINDINGS: A relatively good agreement exists regarding some technical parameters, area of investigation, and assessment of inflammatory activity and chronic damage using magnetic resonance imaging. There are inconsistent data available with respect to distribution of involvement in individual IIM subtypes. Ultrasound and other imaging methods lack the validation and still face many unresolved problems. Imaging plays a crucial role in the evaluation of impairment in patients with IIMs. The future research should be focused on standardization of each method in order to obtain comparable results and on defining the most appropriate indications of their use.

[Office hysteroscopy - management and results]. / Management a výsledky ambulantní hysteroskopie.

OBJECTIVE: Sum up the knowledge about office hysteroscopy. TYPE OF STUDY: Review of literature and our own experience. SETTING: Department of Gynaecology and Obstetrics, First Faculty of Medicine, Charles University Prague and General Teaching Hospital Prague. METHODS: Data from scientific literature and 10 years of our own experience with office hysteroscopy. CONCLUSIONS: Hysteroscopy provides optical evaluation of uterine cavity. Most of the benign intrauterine organics pathologies could be managed in a outpatient setting with a vaginoscopic approach without any anaesthesia and analgesia. Using that approach we can recommend to perform endometrial target biopsy, resection of endometrial polyps up to 1.5 cm and pedunculated submucous myomas up to 1 cm as well as resection of filmy intrauterine adhesions. Method is comfortable for well managed patients and practically complication-free.

[Laparoscopic uterus sparing treatment of uterine fibroids]. / Laparoskopická konzervativní lécba delozních myomu

OBJECTIVE: To report up-to date knowledge on laparoscopic, uterine sparing treatment of uterine fibroids. STUDY DESIGN: Review. SETTING: Uterine Fibroids Center, Department of Obstetrics and Gynecology, Charles University, Prague. METHODS: Analysis of our clinical experience and available literature resources. RESULTS: The management of uterine fibroids depends on the symptoms, location, and size of fibroids and on the reproductive plans of the patient. The surgical treatment has changed from laparotomy to minimally invasive surgery. In general, laparoscopic myomectomy (LM) is considered the best option in symptomatic patients with pregnancy plans. The laparoscopic approach is associated with lower postoperative morbidity as well as lower incidence of massive postoperative adhesion formation compared to laparotomy. The limitation of laparoscopic myomectomy is the size and the number of fibroids but also the location and the accessibility for the laparoscopic suturing. Laparoscopic uterine artery occlusion (LUAO) represents one of the alternatives to LM in patients with multiple small myomas or in patients with fibroids in unfavorable location. LUAO may be advantageously used prior to LM in order to reduce peroperative blood loss or to prevent the persisting fibroids from growing. However there is no universal treatment of uterine fibroids in fertile patients and in each single patient the indication and surgical method should be thoroughly considered. .

[Laparoscopic lymph-node dissection in gynecological surgery]. / Laparoskopická lymfadenektomie v gynekologické operative

OBJECTIVE: To analyze our experience with transperitoneal laparoscopic dissection of lymphatic nodes in women with gynecologic malignancies. STUDY DESIGN: Retrospective clinical study. SETTING: Center of gynecologic endoscopy and minimally invasive surgery; Department of Obstetrics and Gynecology, General Faculty Hospital and 1st Medical Faculty in Prague. METHODS: Analysis of data from our laparoscopic procedures in the years 2006-2011. The following procedures have been included: systematic pelvic lymphadenectomy (PLN), paraaortic lymphadenectomy (PALN), pelvic sentinel node excision, focused dissection of bulky lymphatic nodes from pelvis or paraaortic area. RESULTS: We performed 177 primarily laparoscopic procedures pointed at dissection of pelvic and/or paraaortic lymph-nodes. The mean operating time and the mean number of lymph-nodes was 82 minutes and 26.5 nodes in patients with PLN, and 75 minutes and 12.5 nodes in patients with PALN. The overall rate of laparo-conversions was 4.5%; the incidence of major complications was 6.8% and of serious bleeding 5.6%. Laparoscopic lymphadenectomy could not be performed or completed in 2.3% of cases. Complications were more frequently associated with PALN than with PLN. SUMMARY: Laparoscopic approach to PLN and PALN is feasible in vast majority of patients. It provides adequate earnings of the lymphatic nodes, tolerable operative time, and relatively low complication rate. The highly experienced operation team for especially high infrarenal PALN is necessary.

[Genetic factors in etiology of uterine fibroids]. / Genetické faktory v etiopatogenezi delozních myomu.

Uterine fibroids are the most common pelvic tumors in women of reproductive age. The cause of development of uterine fibroids is still unknown, however recent cytogenetic and genetic studies led to advancement in understanding of etiology of these tumors. In accordance with the latest findings up to 40% of uterine fibroids bear some chromosomal abnormalities. The most common are aberration of chromosomes 6, 7, 12 and 14. Uterine fibroids have been linked to mutations of fumarate hydratase (FH) gene. Germline mutations in FH gene cause autosomal dominant syndromes MCUL1 (multiple cutaneous and uterine leiomyomata) and HLRCC (hereditary leiomyomatosis and renal cell cancer), characterized by multiple uterine and cutaneous leiomyomata and renal cancer. This paper reviews recent findings in the role of genetic in etiology of uterine fibroids.

[Sexual functions after laparoscopically assisted vaginal hysterectomy (LAVH) and total laparoscopic hysterectomy (TLH) in preoperatively asymptomatic women]. / Sexuální funkce po laparoskopicky asistované vaginální es gynek. hysterektomii (LAVH) a totální laparoskopické hysterektomii (TLH) u predoperacne asymptomatických zen.

OBJECTIVE: To find the consequences of laparoscopically assisted vaginal hysterectomy (LAVH) and total laparoscopic hysterectomy (TLH) for sexual functions in preoperatively asymptomatic women. DESIGN: Prospective study. SETTING: Department of Obstetrics and Gynecology, 1st Faculty of Medicine, Charles University and General Teaching Hospital in Prague. MATERIAL AND METHODS: In 100 women without subjective complaints hysterectomy was performed for benign uterine pathology. In all the women the uterus weighted less than 250 g, there were no salpingooophorectomies and no perioperative complications. Women were alternativelly assigned for LAVH (n = 50) or TLH (n = 50). Clinical documentation and questionnaires about sexual functions were evaluated in 87 women (in 40 women after LAVH and in 47 after TLH) 18 months after surgery or later. RESULTS: According to our findings the type of surgery did not influence the frequency of sexual activity after surgery, there was no change in sexual manners using during coitus as well as no change in preferred way how to reach the sexual arousal (clitoridally, vaginally or combined). The type of surgery did not influence frequency, quality and duration of orgasm. From all the evaluated parameters there were only two significantly different: the presence of postoperative sexual activity (positive answer in all women from LAVH group and only in 85% women from TLH group, F test, p = 0.009) and the frequency of sexual satisfaction (in terms of both increase and also decrease in TLH group chi2 8,376, p = 0.015). CONCLUSION: The type of laparoscopic hysterectomy (LAVH or TLH) does not significantly affect the sexual functions (frequency of sexual satisfaction, type of sexual arousability, intensity and duration of orgasm) in preoperatively asymptomatic women.

[News and perspectives in uterine fibroids radiotherapy]. / Novinky a perspektivy v radiologické lécbe delozních myomu.

Uterine artery embolization (UAE) represents radiological treatment of uterine fibroids. It is highly effective and safe mainly in premenopausal patients with symptomatic fibroids and represents an alternative to hysterectomy in a group of women not suitable for minimally invasive surgical treatment (LAVH) and women desiring uterus sparing therapy. The future of UAE lies in optimal selection of patients based on volume-shrinkage prediction and fertility outcome. The second group is represented by methods based on direct fibroid tissue destruction using specific energy under MRI or UZ guidance. The common aim of these two groups is the volume shrinkage as well as the symptomatic relief. The second group is represented by radiofrequency ablation, focused ultrasound surgery, interstitial laser ablation and cryotherapy. Based on their non-surgical, percutaneous approach these can be classified as minimally-invasive methods. The second group of methods is suitable only for patients with the absence of any desire for child bearing due to the absence of their long-term outcome data.

[Spontaneous symphysis pubis rupture followed by intraabdominal bleeding during the vaginal delivery]. / Spontánní ruptura symfýzy následovaná profúzním krvácením do dutiny brianí behem vaginálního porodu.

Symphysis pubis rupture is rare but life-threatening complication of vaginal delivery. Prompt diagnosis and therapy of this complication is crucial. We present a case report of a patient with a symphysis pubis rupture followed by severe intraabdominal bleeding. The therapy of symphysis pubis rupture is usually conservative according to the available sources. In the case of our patient osteosynthesis was performed with an excellent result.

[Methods using ischemia in uterine fibroids treatment]. / Ischemizující metody lécby delozních myomu.

OBJECTIVE: To compare principle, advantages, disadvantages, and risks of conservative (i.e. uterus saving) methods of treatment of uterine fibroids, which are focused on elimination or reduction of their perfusion. To contribute to better understanding of this dynamic topic between gynecologists, especially in the field of appropriate indication criteria. DESIGN: Review article. SETTING: Department of Obstetrics and Gynecology, Charles University and General Faculty Hospital, Prague. METHODS: Analysis of literature and our clinical experience. CONCLUSIONS: Within the last decade the spectrum of treatment of uterine fibroids has broaden with methods causing ischemia of fibroids. These include the minimally invasive surgical therapy (laparoscopic occlusion of uterine arteries /LUAO/ and Doppler assisted laparoscopic myolysis) and radiological catheterization treatment (uterine artery embolization, UAE). Compared to foreign countries where UEA is mainly used in perimenopausal women, we focus on the group of patients with further fertility plans. It is necessary to stress that in spite of the number of affirmative experiences with the new techniques of uterine fibroid treatment in both the indication groups (women with or without further fertility plans) these methods still remain an alternative to standard surgical treatment, because both myomectomy and hysterectomy can be performed by minimally invasive techniques in the majority of women. This review is also focused on the specific risks of the particular methods as well as on their mechanism of action which may dramatically differ despite of some analogies.

Uterine arteries doppler velocimetry provides 3-years follow up endometrial ablation outcome.

The aim of this study was to assess whether uterine artery Doppler velocimetry [pulsatility index (PI) and resistance index (RI)] and thickness of the endometrium (TE) are able to predict 3-year clinical outcome after endometrial ablation (EA) for dysfunctional uterine bleeding (DUB). This was a prospective, observational study of 29 women of whom 22 were amenorrhoeic (A) and 7 eumenorrhoeic (E) at the end of the first postoperative year. The PI, RI and TE were measured prior to and 1, 6 and 12 months after EA. Statistical analyses were performed using BMDP statistical software, discriminant analysis, ANOVA and T test. Using the calculated classification function (CF) with the three parameters PI, RI and TE measured 12 months after FEAT, we were able to accurately (100%) specify which of the women will have A or E in 3 years. The predictive value of PI, RI and TE has been confirmed clinically in a minimum 3-year follow-up of outcome (ranging from 36 to 72 months [mean 55]). All A and E women have stayed in the same group (A or E) during the minimum of 3 years. In conclusion we found that PI, RI and TE measured prior to EA cannot predict the outcome, however these measurements performed 1 year after FEAT can predict the duration of A or E in the 3-year follow up.