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The p73 gene encodes a protein with substantial structural and functional similarities to the tumour-suppressor p53. Alternative splicing of p73 mRNA leads to expression of 6 known RNA species and proteins (α, β, γ, δ, ϵ, ζ). We analysed the expression of these splice variants in ovarian adenocarcinoma by RT-PCR followed by detection of amplicons with the Southern technique and by immunoblot in 32 malignant and benign epithelial ovarian tumour specimens and 3 ovarian adenocarcinoma cell lines (A2780, 2008, OVCAR-3). p73α mRNA was expressed in all 17 ovarian cancer specimens, and 14 of 17 expressed at least 3 splice variants. In contrast, a different expression pattern was present in the ovarian adenomas: p73α was detected in 6 of 12 benign tumours, and only 1 adenoma expressed 3 splice variants. p73 protein was expressed in 9 of 16 ovarian cancer specimens, in all cell lines and in 1 of 3 borderline tumours. In contrast, none of 9 ovarian adenomas expressed detectable amounts of p73 protein. Expression of p73 mRNA and protein was not correlated with FIGO stage and histological grade, but we observed a significant correlation with over-expression of p53 protein. In summary, epithelial ovarian cancers express a more complex p73 isoform pattern and higher levels of p73 mRNA and protein than ovarian adenomas. Int. J. Cancer 88:66–70, 2000. © 2000 Wiley-Liss, Inc.

Objective. The hypercalcemic type of the small cell carcinoma of the ovary (HTSCCO) is a rapidly fatal ovarian tumor in young women. Photodynamic therapy (PDT) induces selective necrosis to malignant tissues. The aim of this study was to determine the sensitivity of the HTSCCO to PDT in a mouse xenograft model. Methods. Tumors were obtained from a patient with a HTSCCO and were transplanted into nude mice. Following photosensitization with m -THPC, either superficial or interstitial laser light was administered to the tumors. Necroses were measured by morphometry. Serum calcium levels were determined prior to and after PDT. Results. Superficial irradiation of m -THPC sensitized tumors showed over three times more necrosis than control tumors ( P = 0.037). Interstitially irradiated tumors showed over seven times more necrosis than control tumors ( P = 0.0012). All animals showed a highly significant hypercalcemia prior to PDT ( P P = 0.0297). Conclusion. This study suggests that PDT may be of therapeutic value for the HTSCCO.

Objective. To investigate the differential diagnostic capacity of the frequency-volume chart in 132 women with urinary incontinence. Material and method. For each patient, the readings of two 24-h frequency-volume charts were compared to the urodynamic diagnosis which was used as the gold standard in 73 genuine stress incontinent women, in 23 urge incontinent women, and in 36 women with mixed incontinence. Results. The total voided volume, the mean voided volume, the largest single voided volume, and the smallest single voided volume were statistically differentiating single parameters among the three groups (p

A 53-year-old woman suffering for 20 years from chronic genitourinary pain was seen in our urogynecological unit. Quality of life assessment by King's Health Questionnaire showed a highly negative impact on quality of life. Clinical examination revealed a painful and swollen distal urethra, and a small fistula was seen located 12 mm proximal to the meatus externus. Perineal ultrasound and magnetic resonance imaging showed multiple cystic formations bilaterally located in the suburethral and paraurethral regions. A diverticulectomy was performed using the vaginal approach. Twelve months after surgery the woman is completely satisfied and only complaining about slight alguria.

BACKGROUND While aortic valve prostheses are known to perform well at rest, few studies have examined them under stress. We compared stress hemodynamics of mechanical valves and nonstented porcine valves in the aortic position to that of normal native aortic valves. METHODS Dobutamine echocardiography was used to assess mean and peak gradients and effective orifice area index (EOAI) at rest and exercise in patients with the Toronto Stentless Porcine Valve (SPV) (n = 13, mean implant size 25.7 mm), Sorin Bicarbon mechanical valve (SOR) (n = 11, mean implant size 24.5 mm), and patients with normal native aortic valves (NOR) (n = 10). Dobutamine infusion was started at 5 micron/kg per minute, and increased by increments of 5 micron/kg per minute until the target heart rate was achieved or until a maximal dose of 40 micron/kg per minute. RESULTS At rest and exercise, respectively, cardiac output (L/min) was 5.2 and 10.4 for Toronto SPV; 7.4 and 13.5 for SOR; and 4.6 and 11.2 for NOR. Measured EOAI (cm2) was 1.1+/-0.2 and 1.15+/-0.2 for TORONTO SPV; 1.60+/-0.3 and 1.58+/-0.3 for SOR; and 1.45+/-0.2 and 1.46+/-0.2 for NOR. Mean gradients (mmHg) were 5.48+/-1.1 and 5.83+/-0.9 for TORONTO SPV; 5.26+/-0.8 and 11.3+/-1.8 for SOR; and 1.54+/-0.4 and 2.18+/-0.7 for NOR. Peak gradients (mmHg) were 11.9+/-2.0 and 21.0+/-3.7 for TORONTO SPV; 10.79+/-1.7 and 25.9+/-3.4 for SOR; and 2.38+/-0.9 and 6.1+/-2.3 for NOR. CONCLUSIONS Although the mechanical group (SOR) had larger measured EOAI, the greater increase in gradients with exercise in this group suggests that the TORONTO SPV is less obstructive to flow.

Optimal migration theory suggests specific scaling relationships between body size and migration speed for individual birds based on the minimization of time, energy, and risk. Here we test if the quantitative predictions originating from this theory can be detected when migration decisions are integrated across individuals. We estimated population-level migration trajectories and daily migration speeds for the combined period 2007-2011 using the eBird data set. We considered 102 North American bird species that use flapping or powered flight during migration. Many species, especially in eastern North America, had looped migration trajectories that traced a clockwise path with an eastward shift during autumn migration. Population-level migration speeds decelerated rapidly going into the breeding season, and accelerated more slowly during the transition to autumn migration. In accordance with time minimization predictions, spring migration speeds were faster than autumn migration speeds. In agreement with optimality predictions, migration speeds of powered flyers scaled negatively with body mass similarly during spring and autumn migration. Powered fliers with longer migration journeys also had faster migration speeds, a relationship that was more pronounced during spring migration. Our findings indicate that powered fliers employed a migration strategy that, when examined at the population level, was in compliance with optimality predictions. These results suggest that the integration of migration decisions across individuals does result in population-level patterns that agree with theoretical expectations developed at the individual level, indicating a role for optimal migration theory in describing the mechanisms underlying broadscale patterns of avian migration for species that use powered flight.

OBJECTIVE The malignant potential of intraepithelial neoplasia of the vulva and vagina after treatment is not well defined. Our objective was to examine risk factors for recurrence and invasive disease. METHODS Four hundred sixty-four women with biopsy proven high-grade intraepithelial neoplasia of the vulva and vagina were identified in the electronic databases of four colposcopy clinics. Inclusion criteria were a follow-up of more than one year, no history of invasive cancer and no invasive cancer within the first year after initial treatment. We investigated the potential factors associated with recurrence and progression using a logistic regression analysis to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS Of the 411 eligible patients, 123 patients (29.9%) recurred later than one year after initial treatment and 24 patients (5.8%) progressed to invasive disease. According to multivariate analyses, the risk factors associated with recurrence were multifocality (OR, 3.33; 95% CI, 2.02 to 5.51), immunosuppression (OR, 2.51; 95% CI, 1.09 to 5.81), excision as initial treatment (vs. laser evaporation; OR, 1.79; 95% CI, 1.11 to 2.91) and smoking (OR, 1.61; 95% CI, 1.02 to 2.55). Risk factors for progression to invasive disease were immunosuppression (OR, 4.00; 95% CI, 1.30 to 12.25), multifocality (OR, 3.05; 95% CI, 1.25 to 7.43) and smoking (OR, 2.97; 95% CI, 1.16 to 7.60), but not treatment modality. CONCLUSION Laser evaporation combined with extensive biopsy is at least as efficacious as initial treatment of intraepithelial neoplasia with excision. Smoking is a risk factor for both recurrence and progression to invasive disease. Hence, smoking cessation should be advised and maintaining a long follow-up period due to late relapses is necessary.

Objective:Medline classifies publications as clinical trials, randomised control trials, meta-analyses, practice guidelines, reviews, case reports, editorials, and letters. We tested the hypothesis that cardiology-related publications have increased with a shift in the type of publications over the past 10 years by age category.Methods:To retrieve from Medline the cardiology articles, we used the keyword “heart disease”, but limited the search to articles in English from 2000 to 2009. We repeated the search using one limit according to the publication type and using age tags. We used regression analysis to determine the effect of the year of publication on the number of publications of each type.Results:During the 10-year period, Medline registered 152,849 cardiology articles, doubling from 10,452 in 2000 to 20,841 in 2009, of which 8.5% were tagged as both paediatric and adult. There was a linear increase in the number over the study period in the total number of publications and in all categories, except for practice guidelines. There was almost a twofold increase in adult and neonatal articles, but ∼70% in paediatric articles. The rate of increase was 66% for randomised control trials, 73% for clinical trials, 124% for meta-analyses, 117% for editorials, 36% for reviews, and 103% for case reports. Practice guidelines remained very low, increasing significantly for paediatric and neonatal articles.Conclusions:There was a substantial increase in cardiology articles over the past 10 years, being greater for adult and neonatal articles compared with paediatric articles. The increase varied according to the type of article.

Detailed $\ensuremath{\alpha}$-decay studies of ${}^{179}$Tl${}^{g}$ and its daughter products ${}^{175}$Au${}^{g}$ and ${}^{171}$Ir${}^{g}$ were carried out in two complementary experiments at the mass separator ISOLDE (CERN) and velocity filter SHIP (GSI). First unambiguous determination of the $\ensuremath{\alpha}$-decay properties of ${}^{175}$Au${}^{g}$ was performed as follows: ${E}_{\ensuremath{\alpha}}$ $=$ 6433(4) keV, ${T}_{1/2}$ $=$ 207(7) ms, and $\ensuremath{\alpha}$-decay branching ratio 90(7)$%$. First determination of the $\ensuremath{\alpha}$-decay branching ratios for ${}^{179}$Tl${}^{g}$ and ${}^{171}$Ir${}^{g}$ was also made: ${b}_{\ensuremath{\alpha}}$(${}^{179}$Tl${}^{g}$) $=$ 60(2)$%$ and ${b}_{\ensuremath{\alpha}}$(${}^{171}$Ir${}^{g}$) $=$ 15(2)$%$. The spins of the ground states in ${}^{175}$Au and ${}^{171}$Ir are established as 1/2${}^{+}$.

Complete guidance for mastering the tools and techniques of the digital revolution With the digital revolution opening up tremendous opportunities in many fields, there is a growing need for skilled professionals who can develop data-intensive systems and extract information and knowledge from them. This book frames for the first time a new systematic approach for tackling the challenges of data-intensive computing, providing decision makers and technical experts alike with practical tools for dealing with our exploding data collections. Emphasizing data-intensive thinking and interdisciplinary collaboration, The Data Bonanza: Improving Knowledge Discovery in Science, Engineering, and Business examines the essential components of knowledge discovery, surveys many of the current research efforts worldwide, and points to new areas for innovation. Complete with a wealth of examples and DISPEL-based methods demonstrating how to gain more from data in real-world systems, the book: Outlines the concepts and rationale for implementing data-intensive computing in organizations Covers from the ground up problem-solving strategies for data analysis in a data-rich world Introduces techniques for data-intensive engineering using the Data-Intensive Systems Process Engineering Language DISPEL Features in-depth case studies in customer relations, environmental hazards, seismology, and more Showcases successful applications in areas ranging from astronomy and the humanities tomore » transport engineering Includes sample program snippets throughout the text as well as additional materials on a companion website The Data Bonanza is a must-have guide for information strategists, data analysts, and engineers in business, research, and government, and for anyone wishing to be on the cutting edge of data mining, machine learning, databases, distributed systems, or large-scale computing.« less

Polycationic cell-penetrating peptides (CPPs) deliver macromolecules into cells without losing the functional properties of the cargoed macromolecule. The aim of this study was to determine whether exogenous cytochrome c is delivered to HeLa cervical carcinoma cells by the CPP antennapedia (Antp) and activates apoptosis. HeLa cervical carcinoma cells were treated with conjugated Antp-SMCC-cytochrome c (cytochrome c chemically conjugated to Antp) or with non-conjugated Antp and cytochrome c. Sensitivity to the treatments was determined by the clonogenic assay (proliferation) and by immunoblot analysis (apoptosis activation). We report that conjugated Antp-SMCC-cytochrome c activated apoptosis in HeLa cells as demonstrated by poly (ADP-ribose) polymerase 1 (PARP-1) cleavage and inhibited their proliferation. The Antp-SMCC-cytochrome c-induced apoptosis was inhibited by z-VAD-fmk, a pan-caspase inhibitor peptide. Unconjugated Antp or cytochrome c demonstrated no inhibitory effect on survival and proliferation. Our results suggest that chemical coupling of cytochrome c to CPPs may present a possible strategy for delivering cytochrome c into cells and for activating apoptosis.

Polycationic cell-penetrating peptides (CPPs) deliver macromolecules into cells without losing the functional properties of the cargoed macromolecule. The aim of this study was to determine whether exogenous cytochrome c is delivered to HeLa cervical carcinoma cells by the CPP antennapedia (Antp) and activates apoptosis. HeLa cervical carcinoma cells were treated with conjugated Antp-SMCC-cytochrome c (cytochrome c chemically conjugated to Antp) or with non-conjugated Antp and cytochrome c. Sensitivity to the treatments was determined by the clonogenic assay (proliferation) and by immunoblot analysis (apoptosis activation). We report that conjugated Antp-SMCC-cytochrome c activated apoptosis in HeLa cells as demonstrated by poly (ADP-ribose) polymerase 1 (PARP-1) cleavage and inhibited their proliferation. The Antp-SMCC-cytochrome c-induced apoptosis was inhibited by z-VAD-fmk, a pan-caspase inhibitor peptide. Unconjugated Antp or cytochrome c demonstrated no inhibitory effect on survival and proliferation. Our results suggest that chemical coupling of cytochrome c to CPPs may present a possible strategy for delivering cytochrome c into cells and for activating apoptosis.

Numerous studies have shown that sentinel lymph node biopsy (SLN) has a high level of detection sensitivity. Successful detection procedure depends on the amount of radioactivity and accumulation of blue dye in the SN. Our aim was to relate the differences observed in intraoperative SN presentation to tumor burden, characteristics of the primary tumor and patient attributes. Our retrospective analysis included 369 patients undergoing SLN in the Department of Gynecology of the University Hospital of Zurich within five years. Data was collected from the patients (age, BMI), the primary tumor (size, grading, hormone receptors, HER2 status) and the SNs removed (counts per second [cps], blue dye, size of nodular metastasis, extracapsular involvement, number of SNs excised). Because patients typically had more than one SN, a linear mixed-effects model was used to account for the clustering within one patient. SNs presented with significantly lower radioactivity in elderly (-1.8%/year, p < 0.001) and obese patients (-3.9%/kg/m2, p = 0.006) as well as in G3 primary tumors (p = 0.002). Radiocolloid accumulation decreased with increasing metastasis size (-6.1%/mm, p = 0.006). In conclusion the detection procedure of SNs is mainly affected by the patient's age and BMI and by nodular metastasis' size. Phagocytotic activity in the lymph node may increase radiotracer accumulation, showing the highest tracer signals in micrometastatic SNs. In large SN metastasis the lymph flow appears obstructed, reducing the axillary drainage and therefore making detection procedure difficult.

Virchows Archiv, 462 (5), ISSN:0945-6317, ISSN:1432-2307

Introduction Overactive bladder syndrome (OAB) is a chronic disorder that often requires long-term treatment. There is a growing interest in new substances. In vitro experiments of Bryophyllum pinnatum (BP) on porcine bladder muscle have shown a muscle-relaxing effect. In this clinical trial we evaluated BP versus placebo regarding efficacy and safety. Materials and methods Prospective, double-blind randomized, placebo-controlled study with 20 patients (10 BP, 10 placebo); medication over 8 weeks; dosage 3 × 2 capsules BP 50% (350 mg)/day or placebo (lactose). Primary aim: reduction of the micturition frequency/24 h. Secondary aim: change in quality of life, alterations of parameters in the bladder diary and adverse events (AE). Statistical analysis was performed with IBM SPSS Statistics 20. The groups were compared using Fisher's exact test and the Mann–Whitney test; the visits using the Wilcoxon signed ranks test. Results Both groups did not differ significantly in demographical data. For the primary endpoint, a trend in the reduction of the micturition frequency/24 h in the BP group was found: 9.5 ± 2.2 before and 7.8 ± 1.2 after BP versus 9.3 ± 1.8 before and 9.1 ± 1.6 after placebo, p = 0.064. From visit 2 to visit 4, micturition frequency/24 h improved in 8/10 patients in the BP group ( p = 0.037). In the placebo group, micturition frequency/24 h improved in 5/9 patients ( p = 0.89). Improvement of the QoL did not differ between the two groups. The incidence of AE was similar in both groups, no SAE occurred. Conclusion The successful safety outcome and positive trend for efficacy permits BP to be further evaluated as a favorable treatment option for OAB.

Seeking new biomarkers for epithelial ovarian cancer, the fifth most common cause of death from all cancers in women and the leading cause of death from gynaecological malignancies, we performed a meta-analysis of three independent studies and compared the results in regard to clinicopathological parameters. This analysis revealed thatGAS6was highly expressed in ovarian cancer and therefore was selected as our candidate of choice.GAS6encodes a secreted protein involved in physiological processes including cell proliferation, chemotaxis, and cell survival. We performed immunohistochemistry on various ovarian cancer tissues and found that GAS6 expression was elevated in tumour tissue samples compared to healthy control samples (). In addition, GAS6 expression was also higher in tumours from patients with residual disease compared to those without. Our data propose GAS6 as an independent predictor of poor survival, suggesting GAS6, both on the mRNA and on the protein level, as a potential biomarker for ovarian cancer. In clinical practice, the staining of a tumour biopsy for GAS6 may be useful to assess cancer prognosis and/or to monitor disease progression.

Objectives Previous studies examining the effectiveness of pelvic floor muscle training (PFMT) for urinary incontinence in premenopausal and postmenopausal women have shown ambiguous results. The aim of this study was to compare subjective PFMT outcome in premenopausal versus postmenopausal women. Methods This is a retrospective study including premenopausal and postmenopausal women after PFMT for urodynamically proven stress urinary incontinence, mixed urinary incontinence, or urgency urinary incontinence from January 2003 to December 2008, with assessment of the need of an incontinence surgery in a follow-up time of least 24 months. Patients evaluated the change of their urinary incontinence on a 4-point Likert scale (1, no improvement; 2, slightly better; 3, no relevant incontinence; 4, excellent outcome; no incontinence at all) and their goal attainment on a 3-point Likert scale (1, less than expected; 2, as expected; and 3, more than expected). Results Successful outcome was reported by 59% of the premenopausal patients and 70% of the postmenopausal patients (P = 0.16), the attainment of the subjective goal by 68% and 81% (P = 0.09), and the need of an incontinence operation in a follow-up of 30 to 102 months by 15% and 14% (P = 1.0), respectively. None of the outcome parameters reached significance. Conclusions In comparing premenopausal to postmenopausal women, we could not detect any statistically significant difference with regard to patients' satisfaction for the outcome of PFMT.

Class I histone deacetylases (HDACs-1-3) play an important role in steroid hormone–dependent gene expression and in modulating cell survival and proliferation. We analyzed their expression in a tissue microarray including 74 endometriosis samples and 30 normal endometrium controls. The mean HDAC-1 immunoreactivity score (IRS ± standard deviation) was 7.6 ± 2.5 in endometriosis and 5.3 ± 2.3 in normal endometrium (P < .001). In contrast, the IRSs of HDAC-2 and -3 were 11.7 ± 0.7 and 11.8 ± 1.1 in endometriosis and 11.6 ± 1.0 and 11.9 ± 0.4 in normal endometrium (P = .7 and P = .2), respectively. Significant correlations were found between HDAC-1 and estrogen (-alpha/-beta) and progesterone receptor expression. In conclusion, HDAC-1, but not HDAC-2/-3, was significantly increased in endometriosis and associated with steroid hormone receptor expression that may reflect interdependence. In context with the literature, specific inhibitors of HDAC-1 may have inhibitory activities similar to those of broad-spectrum HDAC inhibitors and may be clinically tolerated, which would increase their chance as an option in the treatment of endometriosis.

37 cases of extragenital tumours metastatic to the ovaries are analysed from a clinicopathological viewpoint. In 25 out of 334 patients who were operated on between 1978 and 1990 because of a palpable malignant ovarian tumour, ovarian involvement from extragenital cancer was diagnosed. The most frequent primary sites were the stomach (n = 7), colon (n = 6) and breast (n = 6). 4 of the 6 patients with metastatic colon carcinoma had previously documented diagnosis of colon cancer with a time interval between diagnosis of primary tumours and secondary ovarian tumour ranging up to 11 years. Only one patient had a previously known stomach cancer, operated on 32 months earlier. All our patients with gastrointestinal primary tumour died within 1 year (gastric origin) of detection of metastases and 2 years (colon carcinoma) except for one patient with metastasis of colon carcinoma, who is still living after more than 4 years and one patient with gastric carcinoma who survived 34 months after oophorectomy. Surprisingly, ovarian metastases of breast cancer were detected before the primary tumour in 2 out of 6 cases. The other 4 patients were operated on because of an ovarian tumour but had a known and previously operated breast cancer. 27 patients had therapeutic ovarian ablation in metastatic breast cancer without a palpable pelvic mass. None of these patients had symptoms related to the ovaries. In 12 (40%) patients we found microscopic metastases which were bilateral in 9 cases. Metastases to the ovary may not infrequently mimic primary ovarian tumour and are difficult to diagnose preoperatively. We hope that some clinical features described by us (nationality, patient's history, bilateral ovarian tumours in young women) will alert the clinician to investigate further in order to achieve the best possible therapeutic management, because some patients may benefit from adequate treatment and survive for a long time.

We describe an 18-month-old child with idiopathic hypereosinophilic syndrome (IHES) who presented with fever, and cervical lymphadenopathy. Chest X-ray showed marked cardiomegaly, and echocardiogram revealed large pericardial effusion. Other causes of pericarditis were excluded. Despite the initiation of steroid therapy, signs of impending cardiac tamponade developed. Pericardiocentesis yielded bloody fluid with a white blood count of 14,800/mm3, of which 23% were eosinophils. The child recovered after pericardial drainage and prolonged systemic steroid therapy. Eosinophilic pericarditis is a rare but potentially dangerous complication of IHES.

"Checklists" of organisms --- records of the species seen in a specific area during a relatively short time period --- are routinely collected by hobbyists for some taxa of organisms, most notably birds. Gathering and curating these checklists creates a data resource that we believe is underutilized by macroecologists and biogeographers. In this paper, we describe what we perceive to be the strengths of these data as well as caveats for their use. While our comments apply widely to data of this type, we focus on data from eBird, a program that collects checklist data on birds around the world, although principally in the Western Hemisphere.

Checklists of organisms --- records of the species seen in a specific area during a relatively short time period --- are routinely collected by hobbyists for some taxa of organisms, most notably birds. Gathering and curating these checklists creates a data resource that we believe is underutilized by macroecologists and biogeographers. In this paper, we describe what we perceive to be the strengths of these data as well as caveats for their use. While our comments apply widely to data of this type, we focus on data from eBird, a program that collects checklist data on birds around the world, although principally in the Western Hemisphere.

Prolonged intensive care unit (ICU) stay is a surrogate for advanced morbidity or perioperative complications, and resource utilization may become an issue. It is our policy to continue full life support in the ICU, even for patients with a seemingly grim outlook. We examined the effect of duration of ICU stay on early outcomes and late survival.Between 1993 and 2011, 6,385 patients were admitted to the ICU after cardiac surgery. Patients were grouped according to length of stay in the ICU: group 1, 2 days or less (n = 4,631; 73%); group 2, 3 to 14 days (n = 1,423; 22%); group 3, more than 14 days (n = 331; 5%). Length of stay in ICU for group 3 patients was 38 ± 24 days (range, 15 to 160; median 31). Clinical profile and outcomes were compared between groups.Patients requiring prolonged ICU stay were older, underwent more complex surgery, had greater comorbidity, and a higher predicted operative mortality (p0.0001). They had a higher incidence of adverse events and increased mortality (p0.0001). Of the 331 group 3 patients, 60% were discharged: survival of these patients at 1, 3, and 5 years was 78%, 65%, and 52%, respectively. Operative mortality as well as late survival of discharged patients was proportional to duration of ICU stay.Current technology enables keeping sick patients alive for extended periods of time. Nearly two thirds of patients requiring prolonged ICU leave hospital, and of these, 50% attain 5-year survival. These data support offering full and continued support even for patients requiring very prolonged ICU stay.

UNLABELLED Perineal ultrasound was used with a new measurement method that locates the urethrovesical junction. The aim of this study was to test the reproducibility of this examination. Two different investigators examined 40 patients at rest and during Valsalva's manoeuvre. Using a rectangular coordinate system, the bladder neck was located by means of distance measurements. In addition, the retrovesical angle beta was measured as described by Green, and certain anatomical signs were noted. There was a good inter-examiner correlation (r values 0.77-0.92) both at rest and during Valsalva for the distances and angle beta. There was good agreement in the analysis of the anatomical signs. CONCLUSION Perinatal ultrasound, together with the measurement method described in this paper, is a reliable technique for determining the bladder neck position, for measuring angle beta and for analysing anatomical signs. This method permits a quantitative evaluation and quality control of therapeutic procedures.

Tumor infiltrating lymphocytes in primary breast cancer (TIL) are acknowledged measures of disease free survival (DFS) in adjuvant and neoadjuvant settings. Little is known about the biology of metastasis infiltrating lymphocytes (mTIL) although the local immunity of the metastatic site may critically influence the infiltrate composite. To address this question, we compared mTIL with their matched TIL in 87 breast cancer patients and their corresponding distant metastasis at four different anatomical locations. Sections of surgical specimen were immunohistochemically analyzed for CD4(+), CD8(+) and CD20(+) lymphocytes in three different tumor compartments: intratumoral lymphocytes (iTIL) defined as lymphocytes in direct contact with breast cancer cells, stromal lymphocytes (sTIL) located within the intratumoral stromal tissue and invasive-margin lymphocytes (imTIL). Overall, we found fewer (p < 0.001) mTIL than TIL. Within the tumor compartments, imTIL were more frequent than sTIL and iTIL both within metastases and the matched primary tumors (PT) (p < 0.001). CD4(+) T cells were more numerous than CD8(+) T cells and CD20(+) B cells (p < 0.001). There was a similar pattern in PT and their corresponding metastasis. Only patients with brain metastases differed from the others displaying less CD20(+) B cells at the infiltrative margin of the PT (p < 0.05). In summary, mTIL were significantly reduced within metastases but still mirrored the infiltrate pattern of the PT, interestingly regardless of the metastatic anatomical locations investigated. Our results suggest that the PT assigns the infiltrating lymphocyte pattern resumed at the metastatic site.

Kann die Trophoblastpersistenz nach tubenerhaltender, operativer Therapie der Extrauteringraviditat mittels systemischer Methotrexatmedikation erfolgreich behandelt werden? Wir berichten uber eine Patientin mit Trophoblastpersistenz und diskutieren die bisher publizierte Literatur dazu. Mittels systemischer Methotrexattherapie kann eine fur die Patientin vom chirurgischen, anasthesiologischen und psychologischen Standpunkt her belastende Reoperation im beschriebenen Fall wie auch in der uberwiegenden Mehrzahl der publizierten Falle vermieden werden. Aufgrund der vorliegenden Zahlen kann die Methotrexattherapie bei der Trophoblastpersistenz als einfache, effiziente, erfolgreiche und inzwischen etablierte Therapie betrachtet werden.

Migration is a common strategy used by birds that breed in seasonal environments. Selection for greater migration efficiency is likely to be stronger for terrestrial species whose migration strategies require non-stop transoceanic crossings. If multiple species use the same transoceanic flyway, then we expect the migration strategies of these species to converge geographically towards the most optimal solution. We test this by examining population-level migration trajectories within the Western Hemisphere for 118 migratory species using occurrence information from eBird. Geographical convergence of migration strategies was evident within specific terrestrial regions where geomorphological features such as mountains or isthmuses constrained overland migration. Convergence was also evident for transoceanic migrants that crossed the Gulf of Mexico or Atlantic Ocean. Here, annual population-level movements were characterized by clockwise looped trajectories, which resulted in faster but more circuitous journeys in the spring and more direct journeys in the autumn. These findings suggest that the unique constraints and requirements associated with transoceanic migration have promoted the spatial convergence of migration strategies. The combination of seasonal atmospheric and environmental conditions that has facilitated the use of similar broad-scale migration strategies may be especially prone to disruption under climate and land-use change.

The known association between hepatitis B and vasculitis has been reported in rare cases in adults after hepatitis B vaccination. We here describe a 35-day-old infant who developed Kawasaki disease 1 day after receiving his second dose of hepatitis B vaccine. Although extremely rare, this possible side effect should be noted and further investigated.

Objective To investigate whether histone deacetylase inhibitors reduce the expression of the G-protein-coupled estrogen receptor (GPER) and whether the functional inhibition of GPER by the antagonist G-15 decreases the proliferation of endometriotic cells. Design In vitro study. Setting University hospital. Patient(s) Immortalized epithelial endometriotic cells. Intervention(s) Treatment with the histone deacetylase inhibitor romidepsin or suberoylanilide hydroxamic acid (SAHA), or with the GPER antagonist G-15. Main Outcome Measure(s) Western blot analysis and quantitative real-time polymerase chain reaction (PCR) were used to monitor the expression of GPER in response to drug treatment. Effects of GPER stimulation and inhibition on cell proliferation were investigated by the 93-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide (Sigma) (MTT) assay. Result(s) Our results demonstrate that romidepsin and SAHA reduce GPER expression in a concentration-dependent manner. This reduction correlated with the accumulation of acetylated histones. No decreased expression of the estrogen receptor (ER)-α and ERβ was found under comparable experimental conditions. Pretreatment of endometriotic cells with the GPER agonist G-1 stimulated cell proliferation accompanied by rapid Akt phosphorylation. G-15 reversed this stimulation and inhibited cell proliferation, which was accompanied by Akt dephosphorylation. Conclusion(s) G-protein-coupled estrogen receptor is proposed as a potential therapeutic target in endometriosis. The down-regulation of GPER and/or the impairment of its function may reduce the estrogen responsiveness in endometriosis, and therefore might be considered a possible treatment option of endometriosis.

Type II endometrial carcinomas are a highly aggressive group of tumour subtypes that are frequently associated with inactivation of the TP53 tumour suppressor gene. We show that mice with endometrium‐specific deletion of Trp53 initially exhibited histological changes that are identical to known precursor lesions of type II endometrial carcinomas in humans and later developed carcinomas representing all type II subtypes. The mTORC1 signalling pathway was frequently activated in these precursor lesions and tumours, suggesting a genetic cooperation between this pathway and Trp53 deficiency in tumour initiation. Consistent with this idea, analyses of 521 human endometrial carcinomas identified frequent mTORC1 pathway activation in type I as well as type II endometrial carcinoma subtypes. mTORC1 pathway activation and p53 expression or mutation status each independently predicted poor patient survival. We suggest that molecular alterations in p53 and the mTORC1 pathway play different roles in the initiation of the different endometrial cancer subtypes, but that combined p53 inactivation and mTORC1 pathway activation are unifying pathogenic features among histologically diverse subtypes of late stage aggressive endometrial tumours., EMBO Molecular Medicine, 4 (8), ISSN:1757-4676, ISSN:1757-4684

Background The proportion of elderly individuals is growing and the prevalence of chronic kidney disease (CKD) among elderly people undergoing cardiac surgery is increasing constantly. The aim of this study was to determine the influence of different degrees of preoperative renal dysfunction on postoperative outcomes in patients older than 80 years of age. Methods This is an observational study that included adult patients undergoing cardiac surgery in which data were collected prospectively. Patients were divided into groups according to their preoperative plasma creatinine and eGFR levels. Results From February 1997 to January 2010, 318 octogenarians underwent cardiac surgery. Of these, 140 patients (44%) had abnormal preoperative creatinine levels. A significantly higher incidence of postoperative sepsis (4% vs. 17%, p 0.03), CVA (1% vs. 6%, p 0.03), and prolonged hospital stay (16 ± 13 vs. 20 ± 16 days, p 0.04) were detected in patients with preoperative kidney dysfunction. Subgroup analysis revealed that preoperative CKD stage IV (eGFR 15–30 ml/min/1.73 m2) but not CKD stage III (eGFR 30–60 ml/min/1.73 m2) and preoperative creatinine > 1.8 mg/dl were independently associated with increased incidence of postoperative CVA (OR 4; 95% CI 0.07–0. 8, p = 0.05 for eGFR, and OR 7.8; 95% CI 1.2–60, p = 0.003 for creatinine). However, no significant increment in postoperative mortality with decreasing eGFR or increasing preoperative creatinine was demonstrated. Conclusions A substantial increase in the risk of postoperative CVA and sepsis, but not mortality, was demonstrated in octogenarians with advanced but not mild degrees of preoperative CKD. Compared to younger patients, a high burden of comorbidities in octogenarians may have a greater influence on outcomes post cardiac surgery than impaired renal function. Our data may provide a rationale for modified risk stratification in octogenarian candidates for cardiac surgery.

Background The G protein-coupled estrogen receptor (GPER) is thought to be involved in non-genomic estrogen responses as well as processes such as cell proliferation and migration. In this study, we analyzed GPER expression patterns from endometriosis samples and normal endometrial tissue samples and compared these expression profiles to those of the classical sex hormone receptors. Methods A tissue microarray, which included 74 samples from different types of endometriosis (27 ovarian, 19 peritoneal and 28 deep-infiltrating) and 30 samples from normal endometrial tissue, was used to compare the expression levels of the GPER, estrogen receptor (ER)-alpha, ER-beta and progesterone receptor (PR). The immunoreactive score (IRS) was calculated separately for epithelium and stroma as the product of the staining intensity and the percentage of positive cells. The expression levels of the hormonal receptors were dichotomized into low (IRS =6) expression groups. Results The mean epithelial IRS (+/−standard deviation, range) of cytoplasmic GPER expression was 1.2 (+/−1.7, 0–4) in normal endometrium and 5.1 (+/−3.5, 0–12) in endometriosis (p p = 0.71), of ER-alpha 10.6 (+/−2.4, 3–12) and 9.8 (+/−3.0, 2–12; p = 0.26), of ER-beta 2.4 (+/−2.2; 0–8) and 5.6 (+/−2.6; 0–10; p p p p = 0.001), of ER-beta 1.8 (+/−2.0; 0–8) and 5.4 (+/−2.5; 0–10; p p = 0.044), respectively. Cytoplasmic GPER expression was not detectable in the stroma of endometrium and endometriosis. The observed frequency of high epithelial cytoplasmic GPER expression levels was 50% (n = 30/60) in the endometriosis and none (0/30) in the normal endometrium samples (p p = 0.01), as compared to peritoneal (9/18, 50%) or deep-infiltrating endometriotic lesions (7/22, 31.8%). The frequency of high stromal nuclear GPER expression levels was 100% (n = 74/74) in endometriosis and 76.7% (n = 23/30) in normal endometrium (p Conclusions The present data indicate a unique GPER expression pattern in endometriosis, especially in endometriomas as compared to the normal endometrium. The overexpression of GPER in endometriotic lesions suggests a potential role for GPER in the hormonal regulation of endometriosis, which should be taken into consideration for future hormonal treatment strategies.

Introduction and hypothesis: The purpose of this study is to compare retropubic tension-free vaginal tape (TVT) with transobturator out-in TOT and in-out TVT-O for female stress urinary incontinence. Uroflow rate was primary; continence rates, quality of life (QoL) and complication pattern were secondary endpoints. Methods: A prospective randomised trial with 2:1:1 randomisation at two Swiss teaching hospitals. Patients were followed up at 12months. Results: Eighty TVT, 40 transobturator tape (TOT) and 40 TVT-O were randomised. At 12months, there was no difference in Qmax among the groups. Continence was comparable (≥89%). QoL was improved significantly in all groups (P

Background: Activation of the Wnt signaling pathway is implicated in aberrant cellular proliferation in various cancers. In 40% of endometrioid ovarian cancers, constitutive activation of the pathway is due to oncogenic mutations in b-catenin or other inactivating mutations in key negative regulators. Secreted frizzled-related protein 4 (SFRP4) has been proposed to have inhibitory activity through binding and sequestering Wnt ligands. Methodology/Principal Findings: We performed RT-qPCR and Western-blotting in primary cultures and ovarian cell lines for SFRP4 and its key downstream regulators activated b-catenin, b-catenin and GSK3b. SFRP4 was then examined by immunohistochemistry in a cohort of 721 patients and due to its proposed secretory function, in plasma, presenting the first ELISA for SFRP4. SFRP4 was most highly expressed in tubal epithelium and decreased with malignant transformation, both on RNA and on protein level, where it was even more profound in the membrane fraction (p,0.0001). SFRP4 was expressed on the protein level in all histotypes of ovarian cancer but was decreased from borderline tumors to cancers and with loss of cellular differentiation. Loss of membrane expression was an independent predictor of poor survival in ovarian cancer patients (p = 0.02 unadjusted; p = 0.089 adjusted), which increased the risk of a patient to die from this disease by the factor 1.8. Conclusions/Significance: Our results support a role for SFRP4 as a tumor suppressor gene in ovarian cancers via inhibition of the Wnt signaling pathway. This has not only predictive implications but could also facilitate a therapeutic role using epigenetic targets.

Mutations of the tumor-suppressor gene ARID1A result in the loss of protein expression of the BRG-associated factor 250a (BAF250a), a large subunit of transcription-regulating Human SWI/SNF complexes, which have an important role in the control of cell proliferation and tumor suppression. ARID1A mutations are particularly frequent in endometriosis-associated ovarian clear cell and endometrioid carcinomas, and were recently described as a possible key mechanism and early step in the transformation of endometriosis into cancer. Here, we examined the immunohistochemical expression pattern of BAF250a in a tissue microarray including 74 endometriosis and 30 endometrium samples. Ovarian cancer samples (n=136) served as a control. Epithelial BAF250a expression was assessable in 90/104 (87%) and stromal BAF250a expression in 95/104 (91%) of the endometriosis, and endometrium cases due to lack of adequate tissue in some spots. Complete lack of BAF250a expression was observed in three endometriomas (n=3/20, 15%) and one deep-infiltrating endometriosis sample (n=1/22, 5%), but in none of the peritoneal endometriosis (n=0/16) and eutopic endometrium samples (n=0/30). A comparison of the mean immunoreactivity scores revealed a significantly lower expression rate of BAF250a in endometriomas compared with normal endometrium (P

Objective The aim of this study was to summarize the clinical experience at our clinic with pelvic exenteration as a treatment for cervical cancer with special regard to the indications and outcomes of specific patient groups. Methods Medical records of 282 women who underwent pelvic exenteration to treat cervical cancer were analyzed. Results In total, 70 patients (25%) underwent primary exenteration, and 212 (75%) underwent secondary exenteration. Exenteration was anterior for 14 (5%) patients, posterior for 6 (2%) and total for 262 (93%). The overall survival (OS) of the 282 patients was 41% at 5years and 37% at 10years. The disease-free survival at 5years was 61%. For 133 patients for whom pelvic exenteration was a curative procedure, the OS was 64% at 5years and 57% at 10years. For cases of pelvic exenteration as a palliative intervention, the OS was 19% at 5years and 18% at 10years. No difference was seen in the OS at 5years between patients who received primary and secondary operations. No significant difference in the OS was found regardless of whether the patients had positive pelvic lymph nodes, whereas in cases of paraaortic lymph node metastasis, the OS was significantly lower. Out of all of the procedures, 139 (49%) involved no perioperative or postoperative complications. One major complication was reported for 72 (26%) patients, two complications occurred for 42 patients (15%) and more than three complications were noted for 29 (10%) patients. Conclusion Pelvic exenteration is an effective technique with a high percentage of long-term survivors. To the best of our knowledge, our study involves the largest published number of patients treated with pelvic exenteration for a single gynecological cancer and shows that previous contraindications for pelvic exenteration, such as lymph node metastasis (especially when confined to the pelvic lymph nodes), older age or palliative intent, should be reconsidered.

The objective of this study is to assess the value of postcone endocervical curettage, after conization of cervical intraepithelial neoplasia or carcinoma as a predictive tool for residual lesions. This is a retrospective observational study. All data were obtained by the University Hospital of Zurich, Department of Gynaecology. One hundred fifty patients underwent hysterectomy within 12 months after conization and endocervical curettage from 1993 to 2006. To analyze the sensitivity, specificity, and the positive predictive value (PPV) and negative predictive value (NPV) of the endocervical curettage after conization, we used the Fisher exact test and χ(2) test. The main outcome measures are the sensitivity and specificity as well as the PPV and NPV of the postconization endocervical curettage. The endocervical curettage exhibited a sensitivity of 0.38, a specificity of 0.85, a PPV of 0.56, and an NPV of 0.73. Comparing patients younger than 50 years to women 50 years or older, endocervical curettage had a sensitivity of 0.35 and 0.44, a specificity of 0.83 and 0.94, a PPV of 0.46 and 0.88, and an NPV of 0.76 and 0.63, respectively. The endocervical curettage after conization of cervical intraepithelial neoplasia does not generally improve the prediction of residual lesions. However, in women 50 years or older, a higher specificity and PPV, 0.94 and 0.88, respectively, was observed. Therefore, this subgroup of patients may benefit from an endocervical curettage.

In the case of 81 patients, we conducted a perineal ultrasound and a lateral chain urethrocystography under standard conditions. The data collected were compared. The object of this prospective study was, to estimate the comparability of both methods. We also compared, whether the ultrasonically measured values were different between the supine and upright position. The measured values of both methods corresponded at rest, while during strain the values are different. During Valsalva's manoeuvre, the ultrasound method reflects the mobility of the bladder neck better, while the funnelling of the bladder neck can be examined better by lateral chain urethrocystography. The differences between the supine and upright positions were minor in the ultrasound examination, although the funnelling of the bladder neck could be detected better in the upright position. Our study shows that all important measured values can be collected with perineal ultrasound. Except for the funnelling of the bladder neck, typical findings of incontinence can be better shown with perineal ultrasound.

Background Surgery for acute type B aortic dissection is associated with significant mortality. We report the results for 34 consecutive patients who underwent urgent surgery because they met criteria for operation during the acute phase ( Methods The average patient age was 64 (32 to 88) years. Indications for surgery were persistent pain (12), threatened exsanguination (18), malperfusion (renal [3], limb [3]), rapid aortic enlargement (4), and uncontrolled hypertension (1). The mean interval from onset of pain to operation was 7 (1 to 14) days. Resection included the proximal descending aorta in 32, the distal aortic arch in 10, extension to the diaphragm in 10, and involved a thoracoabdominal procedure in 3. Surgical techniques included hypothermic circulatory arrest (16 [47%]), distal bypass, monitoring of somatosensory-evoked potentials, sequential intercostal sacrifice (average, 5.6 pairs), cerebrospinal fluid drainage, and steroid administration. Results There was no hospital mortality. Important complications occurred in 16 patients (47%): 10 respiratory requiring tracheostomy, six infectious, four dialysis, two myocardial infarctions, and two neurologic (one transient stroke, one paraplegia). Mean intensive care unit and hospital stays were 10 (3 to 32) and 35 (7 to 107) days. Survival at 5 and 10 years was 80% and 57%, respectively (mean follow-up, 5.8 years). Conclusions Patients meeting criteria for urgent surgery have a low perioperative risk for mortality and paraplegia, and are relatively free from long-term aorta-related complications. These findings warrant consideration of earlier surgery for appropriate patients with acute type B aortic dissection.