[Vaginal reconstruction for the remedy of pelvic organ prolapse: the effect, influence on urinary and sexual function and quality of life in two-years follow-up Part II - Urinary tract: function and complications]. / Vaginální rekonstrukce prolapsu pánevních orgánu: efekt, komplikace, vliv na mocové a pohlavní funkce a kvalitu zivota ve dvouletém follow-up Cást II - Funkce a komplikace urologické.

OBJECTIVE: To evaluate the effect, risks and benefits of vaginal reconstruction surgery for pelvic organ prolapse (POP). This article (part II of the study) focuses on the urinary tract. DESIGN: Clinical prospective non-randomized trial, two years follow-up. SETTING: Obstetrics and Gynecology Department, Merciful Brothers Hospital, Brno. MATERIALS AND METHODS: The cohort consisted of 410 women who underwent anterior and/or posterior vaginal repair in our hospital in the period from 1. 3. 2012 to 28. 2. 2014. From among the total, 297 women received transvaginal mesh (TVM group, mostly for the higher degree of prolapse), 113 women underwent "native tissue reconstruction" - NT group. The status was evaluated preoperatively, in the early postoperative period and 2 - 6 - 12 and 24 months after the surgery. RESULTS: The incontinence questionnaire ICSI-SF: average score preoperatively, after 12 and 24 months: NT group: 7.1 - 4.5 - 2.6. TVM group: 4.0 - 2.5 - 2.6. Low urinary tract symptoms (LUTS): preoperatively NT group 72% women, mostly combined (impaired both capture and evacuation) in 27.9%, incontinence mixed (MUI) 15.3% and stress (SUI) 9.0%. TVM group - LUTS in 74.3% women, combined difficulties (27.4%) were followed by evacuation problems (16.2%) and 6.8% resp. 3.0% MUI and SUI. Two years after: without any LUTS were 46.1% and 55.3% in the NT resp. TVM group. The most frequented symptom was incontinence (MUI - SUI - UUI in 7.9 - 5.6 - 4.5%), followed by urgency in 5.4% after TVM, whereas in the NT group prevailed UUI (urgent incontinence) 10.1%. Both SUI and combined problems had 7.9% women and MUI resp. urgency was in 4.5% each.Complications according to the International ICS/IUGA classification: T1 (0-48 hours): retention (PVR >100 ml) and/or bacteriuria in the NT group had 11 women (9.7%), in the TVM group 39 women + twice bladder perforation (altogether 13.8%). The maximum of complications was detected in the period T2 and T3 (2-6 resp. 6-12 months after surgery): in the NT group 41.7% resp. 46.0% of controls, in half of them SUI. In the TVM group the overall number of complications was 29.4% resp. 29.1%, the most often was SUI. The last period T4 (over 12 months) - LUTS detected in 37.1% of controls in the NT group, in 23.9% after TVM, in both groups predominantly incontinence (NT: UUI - SUI - MUI in 12.9% - 10.0% and 8.6%, TVM: SUI - MUI - UUI in 8.5% - 6.9% and 3.6%). Other problems were rare. Re-operation for incontinence: in the NT group 11x (10.6%), after TVM surgery 36x (12.1%), with 3 (NT) resp. 15 (TVM) cases for SUI de novo. CONCLUSION: LUT dysfunction develops and/or progresses with the progress of prolapse. Evacuation difficulties are prevalent, often with the occult stress incontinence. Prolapse correcting restores normal miction, SUI may then occur. With the increasing age and time after surgery there is increasing number of mixed and urgent incontinence. With them, women should be counseled and the LUTS should be then lege artis solved.

[Vaginal reconstruction for the remedy of pelvic organ prolapse: the effect, influence on urinary and sexual function and quality of life in two-years follow-upPart I. Vaginal status and complications]. / Vaginální rekonstrukce prolapsu pánevních orgánu: efekt, komplikace, vliv na mocové a pohlavní funkce a kvalitu zivota ve dvouletém follow-upCást I. Vaginální nález a komplikace.

OBJECTIVE: To evaluate the effect, risks and benefits of vaginal reconstruction surgery for pelvic organ prolapse (POP). This article (part I of the study) focuses on the vagina - POP-Q status, complications, re-operations. DESIGN: Clinical prospective non-randomized trial, two years follow-up. SETTING: Obstetrics and Gynecology Department, Merciful Brothers Hospital, Brno. MATERIALS AND METHODS: The cohort consisted of 410 women who underwent anterior and/or posterior vaginal repair (with or without hysterectomy or anti-incontinence procedure) in our hospital in the two years period (1. 3. 2012 - 28. 2. 2014). From among the total, 297 women received transvaginal mesh (TVM group), 113 women underwent "native tissue reconstruction" - NT group. Vaginal status was evaluated pre-operative, in the early postoperative period and 2 - 6 - 12 and 24 month after the surgery. RESULTS: The number of women that had come to the vaginal investigation at 2 - 6 - 12 - 24 month in NT group: 96 - 49 - 58 - 65, in TVM group: 277 - 218 - 228 - 222. All percentage relates then to the number of vaginally checked cases in the appropriate time. The most distal point of vagina: NT group - preoperative mean 1,12 (median +1), after two years mean -1,30 (median -1). Vaginal wall reaching hymen or 1 cm under it found in 24 women (36.9%), POP stage III, IV, i.e. decrease 2 cm, was in two women (3.1%). TVM group: preoperative mean 2.93 (median +2), after two years mean -1.73 (median -2). Prolapse 0-1 cm under hymen developed in 39 women (17.6%), POP stage III, IV found in five women (2.3%). Clinically significant complications (symptomatic and/or dehiscence >1 cm) in the hospital period and after 2 - 6 - 12 - 24 month in NT group: 3.5% - 12.5% - 2% - 0 - 0 of the checked women, in TVM group these numbers were 3.5% - 12.3% - 8.7% - 6.1% - 3.2%. Reoperation for recurrent POP: in NT group once (0.9%), in TVM group three times (1.0%). Reoperation for vaginal complication after NT operation: six times (5.3%), after TVM procedure 15 times (5.1%). Protrusion resection from the above done in nine cases (three times resection itself, six times in combination with another indication). CONCLUSION: The vaginal reconstruction of POP has a good effect with acceptable rate of complications. The NT procedure had the higher percentage of POP recurrence (40% vs 19.9%), the TVM surgery had more late vaginal complications (6...3% vs 0 after NT). Number of re-operations for vaginal complications was similar in both groups (about 5%).

[Registry of the urogynaecologic procedures involving implant in the Czech Republic during the year 2007]. / Registr urogynekologických výkonu s implantáty v Ceské republice za rok 2007.

OBJECTIVE: The aim of this paper is to report the outcomes of the registry of the urogynaecologic procedures involving implant in the Czech Republic during the year 2007. SUBJECT: Retrospective registry analysis. SETTING: Czech Urogynaecological Association, Prague. SUBJECT AND METHOD: We performed a retrospective analysis of all urogynaecologic procedures involving implant registered in the Czech Registry during the year 2007. CONCLUSION: We report the results of 2557 urogynaecologic procedures involving implant from the 33 referring centres from the Czech Republic. 2232 (87%) implants were intended to treat the stress urinary incontinence and 325 (13%) were used to treat the pelvic organ prolapse. Intraoperative complications were reported in 36 (1.41%) cases, early postoperative complications intervened in 117 cases (4.58%) and the late complications were found in 121 females (4.73%).

[Effect of cranberry extract capsules taken during the perioperative period upon the post-surgical urinary infection in gynecology]. / Perioperacní podávání kapslí s brusinkovým extraktem 7 gynek v profylaxi uroinfekcí po gynekologických operacích.

OBJECTIVE: To evaluate the effect of cranberry extract capsules taken during the perioperative period upon the post-surgical urinary infection (UTI) in gynecology. DESIGN: Clinical prospective pilot trial. SETTING: Obstetrics and Gynecology Department, Merciful Brothers Hospital, Brno and Obstetrics and Gynecology Department, Charles University 2nd Medical Faculty and Teaching Hospital Motol, Prague. MATERIALS AND METHODS: The cohort consisted of 286 women who underwent hysterectomy and/or anterior vaginal repair (with or without anti-incontinence operation) in the above hospitals in the period 1. 9. 2006 -30. 6. 2007. 132 women from among the total were given cranberry extract capsules (equiv. 17,000 mg of fresh fruit) twice a day, 4 days before and 5 days after the surgery. The rest were the control group. The clinical state and the analysis of catheterized urine including bacteriology were determined on the day of surgery and on the 6th postoperative day. Cases with preoperative UTI and those with antibiotic therapy (due to other than urology indications) were excluded from the study. Thus the statistical analysis was made in the remaining 117 patients with prophylactic cranberry capsules and 139 controls. RESULTS: There were 30.8% of positive cultured urines, 18.0% of pyuric specimens and 6.8% symptomatic urinary infections in the group of cranberry prophylaxis. Controls had significant bacteriuria in 27.3%, pyuria in 23.7% and symptomatic UTI in 5.0%. Differences were not statistically significant. CONCLUSION: The intake of cranberry extracts in the perioperative period (4 days before and 5 days after the surgery) did not affect the number of post-surgical UTIs.

[Risk factors for postsurgical uroinfection in gynecology]. / Rizikové faktory uroinfekcí po gynekologických operacích.

OBJECTIVE: This study eims to evaluate risk factors for postsurgical uroinfection (UTI) in gynecology. DESIGN: Clinical retrospective trial. SETTING: Obstetrics and Gynecology Department, Merciful Brothers Hospital, Brno. MATERIALS AND METHODS: All of 290 women who underwent hysterectomy and/or anterior vaginal repair (with or without anti-incontinence operation) in our hospital during the year 2005 were studied. The following data were noted: age, weight, anamnestic UTI, diabetes, other serious morbidity, moving disorders, estrogene deficiency, the type of surgery, the type of catheter and the duration of its indweling, intra/postoperative complications, urologic symptoms and urine analysis including bacteriology on the 6th postoperative day. There were excluded cases with antibiotic therapy (due to non-urological indications) from the study. The risk factors were assessed on the rest of 262 women, in two subgroups according to the catheter type (Foley/minicatheter), as there were remarcable differences in the indwelling time and other characteristics. "Mini-catheter" (a thin transurethral catheter) enables spontaneous voiding as well as measuring the postmiction residuum. It was used in case of anterior vaginal repair or Burch operation and extracted as soon as the voiding function had been restored, mostly on the 2nd-3rd day. The Foley was used in the others, mostly for one day. The unidimensional (Fisher and Mann-Whitney test) and multidimensional (logit model, Walds statistic) analyses were performed. The influence of the type of catheter itself was analysed within an indwelling time period (20-32 hours) in which women of both subgroups were present. RESULTS: The Foley group (115 women, indwelling time 16-32 hours) had 3.5% UTI, none of studied factors was estimated as significant. In the mini-catheter group (147 women, catheterisation for 20-234 hours) was 35.4% UTI, with two risk factors: the time of catheterisation (p = 0.000029) and complications (p = 0.021515). The statistic model we have used (logit analysis) predicts UTI with sensitivity 61.5 and specificity 89.5. There was no difference in the risk of UTI between the two types of used catheters in case of equal time of their insertion. CONCLUSION: Postsurgical UTI was connected significantly with the duration of catheterisation and intra/postoperative complications. In case of short time catheterisation (up to 32 hours), however, the percentage of UTI was low and no risk factor was assessed as significant.

[Extraction of the head at breech delivery]. / Extrakce hlavicky u porodu koncem pánevním.

OBJECTIVE: Review of method of head extraction at breech delivery. DESIGN: Review of literature. SETTING: Department Gynecology and Obstetric Nemocnice Milosrdných bratrí, Brno. METHODS: Review of textbooks, articles obtained through MEDLINE and authors' experience. RESULTS: Entrapment of head at breech delivery is a serious complication in about 8% deliveries. Two methods for extraction of head are available: forceps and manual maneuver. We compare advantage and disadvantage of both approaches and their evaluation in literature particularly in the Czech one. We describe own experience with forceps for after coming head. CONCLUSION: We find no evidence that these two methods exert different influence on perinatal outcome. Preference of one of them depends on tradition and conventions of the department. Obstetrician, familiar with forceps for cephalic presentation, need not be afraid to use this procedure for after coming head.

[External cephalic version in breech presentation of fetus]. / Obrat plodu naléhajícího koncem pánevním zevními hmaty.

OBJECTIVE: Comprehensive information on external cephalic version. DESIGN: Review of literature. SETTING: Department Gynecology and Obstetrics, Nemocnice Milosrdných bratrí, Brno. SUBJECT AND METHOD: Review of reasons, conditions, contraindications, technique, results, and complications of external cephalic version. CONCLUSION: External cephalic version is safe, simple and cheap procedure which should be applied as a common part of management of breech presentation.

[Quality of life in women after urogynecologic surgery]. / Kvalita zivota zen po urogynekologických operacích.

OBJECTIVE: The aim of this study is to verify the change in the quality of life, by a subjective assessment of women, following their surgery for stress incontinence. We also evaluate any connection with postoperative complications. DESIGN: A pilot prospective study. SETTING: Department of Obstetrics and Gynecology General Faculty Hospital, 1st Medical Faculty, Charles University, Prague. METHODS: Quality of life is measured in accordance with the results of a questionnaire. We chose to use a standardized questionnaire by Donald L. Patrick "Incontinence of Life Instrument" (I-QoL). I-QoL consists of 22 subjects of measure, each with a five point scale, addressing various aspects of urine incontinence. We assessed the percentage results of I-QoL before and between 3-6 months after surgery for a connection to postoperative complications. RESULTS: Our patient set was 64 women, all of whom had undergone an operation for stress incontinence. The most common was Kolpopexis secundum Burch at 74%. The average age of the subjects was 54. 59.4% of those tested displayed BMI in excess of 25, whilst 49% of the women had previously undergone laparotomy surgery. The average value of I-QoL before the operation was 46.21%. In the second reading, post operation, this had risen to 80.86%. The difference of 34.65% strongly suggests a significant rise in the quality of life following the operation. 68.74% (44x) of the women were significantly improved, meaning their quality of life had increased by at least 13%. 12.5% (8x) showed slight improvement, 14.07% (9x) maintained their quality of life, and just 4.68% (3x) showed signs of deterioration. We found the biggest improvements in those suffering with stress incontinence. The patients felt generally more healthy, helping to reduce the depression and anxiety associated with incontinence. In contrast, our treatment caused a case of postoperative urgency and nycturia. CONCLUSION: Early complications had no impact on the quality of life, but those which came later--urgency and nycturia did. The result of I-QoL generally depends on the intensity of difficulties before the operation. The question to ask is, whether the subjective assessment can ever be used as a comparison to the objective research.

[Long-term use of combined hormonal contraception--myths and reality]. / Dlouhodobé uzívání kombinované hormonální kontracepce--mýty a realita.

OBJECTIVE: To assess relationship of long-term use of combined oral contraception (COC) and women health, discussion about myths connected with use of COC. DESIGN: Review of literature. SETTING: Department of Obstetrics and Gynaecology, Hospital of Merciful Brothers, Brno, Czech Republic. METHODS: Identification of studies able to address the topic using Medline database search. RESULTS: Besides reliable control of fertility COC protect women against dysmenorrhea, iron deficiency anemia, ovarian cysts and uterine fibroids. COC plays very important role in gynecologic endocrinology suppressing effectively hyperandrogenism, which has not only cosmetic effect but brings also improvement in cardiovascular health of affected perimenopausal women. Premenopausal using of COC could help preserve bone mineral density and can reduce the risk of developing Alzheimer's disease. The most important feature is protective effect against endometrial (by 70%) and ovarian (by 50%) cancer which increases with duration of COC use and is long lasting and may be observed 15 to 20 years after stopping use. Association of use COC with increased risk neither of cervical cancer nor breast cancer has not been confirmed. Controversy still persists over the association of long-term (longer than 8 years) COC use by young nulliparas and breast cancer. The risk in this group of users is probably slightly increased. But no authorities recommended any restriction of COC's prescription. Some studies have suggested an inverse relationship between use of COC and risk of colorectal cancer. The only established evidence of direct association between OC use and cancer risk is the increased risk for hepatocellular carcinoma in the absence of hepatitis B (but maximum by 4 cases per 1,000,000 users per year). CONCLUSION: Most non-contraceptive health benefits of COC are still not widely appreciated in spite of much evidence. The final decision of contraception method is upon well and adequate informed user by well educated doctor.

Ras activation in normal white blood cells and childhood acute lymphoblastic leukemia.

Ras is an important cellular switch, relaying growth-promoting signals from the plasma membrane to the nucleus. In cultured cells, Ras is activated by various hematopoietic cytokines and growth factors, but the activation state of Ras in peripheral WBCs and bone marrow cells has not been studied nor has Ras activation been assessed in cells from patients with acute lymphoblastic leukemia (ALL). Using an enzyme-based method, we assessed Ras activation in peripheral WBCs, lymphocytes, and bone marrow cells from normal subjects and from children with T-cell ALL (T-ALL) and B-lineage ALL (B-ALL). In normal subjects, we found mean Ras activations of 14.3, 12.5, and 17.2% for peripheral blood WBCs, lymphocytes, and bone marrow cells, respectively. All three of these values are higher than we have found in other normal human cells, compatible with constitutive activation of Ras by cytokines and growth factors present in serum and bone marrow. In 9 of 18 children with T-ALL, Ras activation exceeded two SDs above the mean of the corresponding cells from normal subjects, whereas in none of 11 patients with B-ALL did Ras show increased activation; activating genetic mutations in ras occur in less than 10% of ALL patients. Thus, Ras is relatively activated in peripheral blood WBCs, lymphocytes, and bone marrow cells compared with other normal human cells, and Ras is activated frequently in T-ALL but not in B-ALL. Increased Ras activation in T-ALL compared with B-ALL may contribute to the more aggressive nature of the former disease.

Inhibition of phosphatidylinositol 3-kinase activity by adenovirus-mediated gene transfer and its effect on insulin action.

Phosphatidylinositol 3-kinase (PI 3-K) is implicated in cellular events including glucose transport, glycogen synthesis, and protein synthesis. It is activated in insulin-stimulated cells by binding of the Src homology 2 (SH2) domains in its 85-kDa regulatory subunit to insulin receptor substrate-1 (IRS-1), and, others. We have previously shown that IRS-1-associated PI 3-kinase activity is not essential for insulin-stimulated glucose transport in 3T3-L1 adipocytes, and that alternate pathways exist in these cells. We now show that adenovirus-mediated overexpression of the p85N-SH2 domain in these cells behaves in a dominant-negative manner, interfering with complex formation between endogenous PI 3-K and its SH2 binding targets. This not only inhibited insulin-stimulated IRS-1-associated PI 3-kinase activity, but also completely blocked anti-phosphotyrosine-associated PI 3-kinase activity, which would include the non-IRS-1-associated activity. This resulted in inhibition of insulin-stimulated glucose transport, glycogen synthase activity and DNA synthesis. Further, Ser/Thr phosphorylation of downstream molecules Akt and p70 S6 kinase was inhibited. However, co-expression of a membrane-targeted p110(C) with the p85N-SH2 protein rescued glucose transport, supporting our argument that the p85N-SH2 protein specifically blocks insulin-mediated PI 3-kinase activity, and, that the signaling pathways downstream of PI 3-kinase are intact. Unexpectedly, GTP-bound Ras was elevated in the basal state. Since p85 is known to interact with GTPase-activating protein in 3T3-L1 adipocytes, the overexpressed p85N-SH2 peptide could titrate out cellular GTPase-activating protein by direct association, such that it is unavailable to hydrolyze GTP-bound Ras. However, insulin-induced mitogen-activated protein kinase phosphorylation was inhibited. Thus, PI 3-kinase may be required for this action at a step independent of and downstream of Ras. We conclude that, in 3T3-L1 adipocytes, non-IRS-1-associated PI 3-kinase activity is crucial for insulin's metabolic signaling, and that overexpressed p85N-SH2 protein inhibits a variety of insulin's ultimate biological effects.

[Hemostasis using vasopressin analogs during conization of the uterine cervix and minor vaginal operations]. / Hemostáza analogy vazopresinu pri konizacích cípku a pri malých vaginálních operacích.

Peroperative haemorrhage is a frequent complication of conization of the portio uteri by surgery-by a "cold knife" scalpel or another method (LEEP, laser, etc.). In a clinical study comprising 41 patients with the diagnosis CIN I-III or laceration of the portio uteri classical conization by means of a scalpel was made with concurrent haemostasis with terlipressin (TLP) by paracervical administration (400 micrograms-REMESTYP 2 amp.). Concurrently the blood loss in ml was followed, the Hb level and other effects of the preparation. From the results ensues that side-effects after local administration of TLP were observed only in 12.2%. Peroperative blood losses were on average under 15 ml. Local paracervical TLP administration appears effective from the clinical aspect with regard to the low frequency of side-effects and the favourable haemostatic effect.

A decrease in the intracellular guanosine 5'-triphosphate concentration is necessary for granulocytic differentiation of HL-60 cells, but growth cessation and differentiation are not associated with a change in the activation state of Ras, the transforming principle of HL-60 cells.

We found that when human promyelocytic leukemic cells (HL-60 cells) were induced to differentiate along the granulocytic lineage by two diverse mechanisms (starvation for an essential amino acid or treatment with DMSO), there was a marked decrease in the intracellular guanosine 5'-triphosphate (GTP) concentration with no change in the guanosine 5'-diphosphate (GDP) concentration. Differentiation was prevented by guanine or guanosine in a dose-dependent manner. We showed that: (a) guanine had to be converted to a nucleotide because it did not prevent differentiation of hypoxanthine-guanine phosphoribosyltransferase-deficient HL-60 cells; (b) the effect of guanine correlated with a return of the cytosolic GTP:GDP ratio to normal; and (c) other purine bases were not effective. We hypothesized that the decreased GTP:GDP ratio in differentiating HL-60 cells might decrease the relative amount of GTP bound to Ras, a key regulatory GTP-binding protein important to cell growth and differentiation. Consistent with data showing that HL-60 cells harbor an activating N-Ras mutation, we found that the percentage of Ras molecules in the GTP-bound state was high in proliferating HL-60 cells (27 +/- 3%) compared with other cultured mammalian cells (< 1%); however, we found no change in the activation state of Ras when cells ceased to proliferate and differentiated in response to DMSO, amino acid deprivation, or inhibitors of guanylate synthesis. We conclude that: (a) a decrease in the intracellular GTP concentration is necessary for HL-60 cells to undergo granulocytic differentiation; and (b) although a high degree of Ras activation contributes to the malignant phenotype of the cell, there is no change in the activation state of Ras during granulocytic differentiation.

Enhanced tumorigenic behavior of glioblastoma cells expressing a truncated epidermal growth factor receptor is mediated through the Ras-Shc-Grb2 pathway.

A mutant epidermal growth factor receptor (DeltaEGFR) containing a deletion of 267 amino acids from the extracellular domain is common in human glioblastomas. We have previously shown that the mutant receptor fails to bind EGF, is constitutively phosphorylated, and confers upon U87MG glioblastoma cells expressing it (U87MG. DeltaEGFR), an increased ability to form tumors in mice. Here we demonstrate that the constitutively phosphorylated DeltaEGFR enhances growth of glioblastoma cells through increased activity of Ras: 1) there was an increase in the proportion of Ras present in the GTP-bound form, and 2) introduction of neutralizing anti-Ras 259 antibodies into U87MG and U87MG.DeltaEGFR cells by microinjection inhibited DNA synthesis to the same low level in both cell populations. We also show that the truncated EGF receptor constitutively associates with the adapter proteins Shc and Grb2 which are involved in the recruitment of Ras to activated receptors. Several derivatives of DeltaEGFR containing single, or multiple mutations at critical autophosphorylation sites were constructed and used to demonstrate that the major Shc binding site is Tyr-1148, and that Grb2 association occurs primarily through Tyr-1068. We conclude that the increased tumorigenic potential of glioblastoma cells expressing the truncated EGF receptor is due at least in part to Ras activation presumably involving the Shc and Grb2 adapter proteins.

Regulation of gene expression by cGMP-dependent protein kinase. Transactivation of the c-fos promoter.

The cAMP/cAMP-dependent protein kinase (A-kinase) and Ca2+/calmodulin-dependent protein kinase (Cam-kinase) signal transduction pathways are well known to regulate gene transcription, but this has not been demonstrated directly for the cGMP/cGMP-dependent protein kinase (G-kinase) signal transduction pathway. Here we report that transfection of G-kinase into G-kinase-deficient cells causes activation of the human c-fos promoter in a strictly cGMP-dependent manner. The effect of G-kinase appeared to be mediated by several sequence elements, most notably the serum response element (SRE), the AP-1 binding site (FAP), and the cAMP response element (CRE). The magnitude of G-kinase transactivation of the fos promoter was similar to that of A-kinase, but there were significant differences between G-kinase and A-kinase activation of single enhancer elements and of a chimeric Gal4-CREB transcription factor. Our results indicate that G-kinase transduces signals to the nucleus independently of A-kinase or Ca2+, although it may target some of the same transcription factors as A-kinase and Cam-kinase.

Ras-GTP levels are elevated in human NF1 peripheral nerve tumors.

Neurofibromin, the gene product of NF1, is a Ras GTPase Activating Protein. The absence of neurofibromin leads to increased levels of Ras-GTP, which contributes to the proliferation of NF1 neurogenic sarcoma cell lines. Whether this pathogenic mechanism is applicable to benign and malignant peripheral nerve tumours from NF1 and non NF1 patients is not known, due to lack of a tissue based assay. We have adapted a colorimetric enzymatic assay for determining levels of Ras bound guanine nucleotides in tissues. Ras-GTP levels were increased in NF1 neurogenic sarcomas (15 times) and benign NF1 neurofibromas (four times), compared to non NF1 schwannomas. Neurofibromin was not expressed in NF1 sarcomas, in support of its important negative Ras regulatory role in the pathogenesis of NF1 peripheral nerve tumors.

[Hysteroscopic sterilization using Ovabloc]. / Hysteroskopická sterilizace Ovablokem.

The authors give an account on 29 sterilizations made by the hysteroscopic route, using the preparation OVABLOC. It is a reversible block of the oviducts by occlusive material. Under hysteroscopic control into the inner orifice of the oviduct by means of a special injecting device under pressure a two-component mixture of silicone and a catalyst is instilled which causes within 5 min. hardening of the mass and the formation of an elastic relief filling of the entire oviduct. In 25 of the women (86.2%) the procedure was accomplished without complication, in the 3 (10.3%) the procedure failed on account of technical difficulties and in one case (3.5%) during hysteroscopy the uterine wall was perforated. On X-ray check-up after three months of 25 successfully operated women in 24 the position of the tubal occlusion was unaltered (the material is due to dispersed silver particles contrasting on X-ray); in one case it was loosened. The advantages of the method are that it is sparing, well tolerated and easily reversible, the disadvantage is that it is relatively laborious and expensive.