Unilateral pectineal suspension - A new surgical approach for apical correction of pelvic organ prolapse.

Background and objectives: There are numerous vaginal and abdominal surgical approaches for the treatment of pelvic organ prolapse (POP). Even the standard techniques show great variability due to modifications depending on anatomy, available instruments and materials. Recently, the role of hysterectomy in prolapse surgery as well as the use of synthetic meshes have been questioned. Here, we present a standardised mesh-free minimally invasive pelvic floor reconstruction technique with uterus preservation. Materials and Methods: Unilateral pectineal suspension (UPS) is carried out in five defined steps with the use of the da Vinci Xi ® surgical system. The desired anatomical result is simulated by intraoperative uterus manipulation. The cranial part of the pectineal ligament is used for lateral fixation. A non-absorbable suture is placed between the pectineal ligament and the anterior cervix to suspend the uterus in its natural anatomical position. Main outcome measures: For outcome measurement, degree of prolapse was assessed pre- and postoperatively according to the POP-Q system. Results: Unilateral pectineal suspension offers several advantages. Medial tension-free positioning of the uterus is achieved. The use of the cervix as fixation structure allows for excellent pelvic floor support and stable results. Normal pelvic floor mobility and natural axis of the vagina are restored. Conclusions: Unilateral pectineal suspension is an efficient minimal-invasive mesh-free procedure which allows uterus preservation and offers reliable level I support respecting the physiological pelvic anatomy. In addition, there is no need for ureteral dissection or bowel manipulation. The technique offers clinical standardization and can easily be integrated into the spectrum of modern surgical POP repair.

Complementary and alternative medicine and musculoskeletal pain in the first year of adjuvant aromatase inhibitor treatment in early breast cancer patients.

BACKGROUND: Patients with breast cancer (BC) show strong interest in complementary and alternative medicine (CAM), particularly for adverse effects of adjuvant endocrine treatment - e.g., with letrozole. Letrozole often induces myalgia/limb pain and arthralgia, with potential noncompliance and treatment termination. This analysis investigated whether CAM before aromatase inhibitor (AI) therapy is associated with pain development and the intensity of AI-induced musculoskeletal syndrome (AIMSS) during the first year of treatment. PATIENTS AND METHODS: The multicenter phase IV PreFace study evaluated letrozole therapy in postmenopausal, hormone receptor-positive patients with early BC. Patients were asked about CAM use before, 6 months after, and 12 months after treatment started. They recorded pain every month for 1 year in a diary including questions about pain and numeric pain rating scales. Data were analyzed for patients who provided pain information for all time points. RESULTS: Of 1396 patients included, 901 (64.5%) had used CAM before AI treatment. Throughout the observation period, patients with CAM before AI treatment had higher pain values, for both myalgia/limb pain and arthralgia, than non-users. Pain increased significantly in both groups over time, with the largest increase during the first 6 months. No significant difference of pain increase was noted regarding CAM use. CONCLUSIONS: CAM use does not prevent or improve the development of AIMSS. Pain intensity was generally greater in the CAM group. Therefore, because of the risk of non-compliance and treatment discontinuation due to the development of higher pain levels, special attention must be paid to patient education and aftercare in these patients.

Influence of side-effects on early therapy persistence with letrozole in post-menopausal patients with early breast cancer: Results of the prospective EvAluate-TM study.

BACKGROUND: Endocrine treatment (ET) with an aromatase inhibitor (AI) is the treatment of choice in post-menopausal patients with hormone receptor-positive early breast cancer (EBC). However, adverse events (AEs) often lead to treatment discontinuation. This analysis aimed to identify side-effects that lead to patients failing to persist with letrozole treatment. PATIENTS AND METHODS: Post-menopausal hormone receptor-positive EBC patients starting ET with letrozole were enroled in EvAluate-TM, a non-interventional study. Information regarding treatment compliance and persistence was gathered in months 6 and 12. Persistence was defined as the time from 30 d after the start to the end of treatment. The influence on persistence of musculoskeletal syndrome, menopausal disorder, sleep disorder and other AEs within the first 30 d was analysed using Cox regression analyses. RESULTS: Among 3887 patients analysed, the persistence rate after 12 months was >85%. In all, 568 patients (14.6%) discontinued the treatment, 358 of whom (63.0%) did so only because of side-effects. The main AEs influencing persistence were musculoskeletal symptoms (hazard ratio [HR] 2.55; 95% confidence interval [CI], 1.90-3.42), sleep disorders (HR 1.95; 95% CI, 1.41-2.70) and other AEs (HR 2.03; 95% CI, 1.51-2.73). Menopausal disorder was not associated with non-persistence (HR 1.17; 95% CI, 0.74-1.84). CONCLUSIONS: These results suggest that side-effects of AIs such as musculoskeletal syndrome and sleep disorder lead to ET discontinuation within the first treatment year in significant numbers of EBC patients. Compliance programmes adapted for subgroups that are at risk for early non-persistence might help to ensure the recommended therapy duration. CLINICAL TRIALS NUMBER: CFEM345DDE19.

Influence of patient and tumor characteristics on early therapy persistence with letrozole in postmenopausal women with early breast cancer: results of the prospective Evaluate-TM study with 3941 patients.

Background: Patients' compliance and persistence with endocrine treatment has a significant effect on the prognosis in early breast cancer (EBC). The purpose of this analysis was to identify possible reasons for non-persistence, defined as premature cessation of therapy, on the basis of patient and tumor characteristics in individuals receiving adjuvant treatment with letrozole. Patients and methods: The EvAluate-TM study is a prospective, multicenter, noninterventional study in which treatment with the aromatase inhibitor letrozole was evaluated in postmenopausal women with hormone receptor-positive EBC in the early therapy phase. Treatment persistence was evaluated at two pre-specified study visits after 6 and 12 months. As a measure of early therapy persistence the time from the start to the end of treatment (TTEOT) was analyzed. Cox regression analyses were carried out to identify patient characteristics and tumor characteristics predicting TTEOT. Results: Out of the total population of 3941 patients with EBC, 540 (13.7%) events involving treatment cessation unrelated to disease progression were observed. This was due to drug-related toxicity in the majority of cases (73.5%). Persistence rates were 92.2%, 86.9%, and 86.3% after 6, 12, and 15 months, respectively. The main factors influencing premature treatment discontinuation were older age [hazard ratio (HR) 1.02/year], comorbidities (HR 1.06 per comorbidity), low body mass index, and lower tumor grade (HR 0.85 per grade unit). Conclusion: These results support the view that older, multimorbid patients with low tumor grade and low body mass index are at the greatest risk for treatment discontinuation and might benefit from compliance and support programs.

A Review of Integrative Medicine in Gynaecological Oncology.

In recent years complementary and alternative medicine (CAM) has increasingly been the focus of international research. Numerous subsidised trials (7903) and systematic reviews (651) have been published, and the evidence is starting to be integrated into treatment guidelines. However, due to insufficient evidence and/or insufficient good quality evidence, this has mostly not translated to practice recommendations in reviews by the Cochrane collaboration gynaecology group. There is nevertheless a not insignificant number of CAM providers and users. The percentage of oncology patients who use CAM varies between 5 and 90 %. Doctors have been identified as the main providers of CAM. Half of gynaecologists offer CAM because of personal conviction or on suggestion from colleagues. This must be viewed in a critical light, since CAM is mostly practiced without appropriate training, often without sufficient evidence for a given method - and where evidence exists, practice guidelines are lacking - and lack of safety or efficacy testing. The combination of patient demand and lucrativeness for doctors/alternative medicine practitioners, both based on supposed effectiveness CAM, often leads to its indiscriminate use with uncertain outcomes and significant cost for patients. On the other hand there is published, positive level I evidence for a number of CAM treatment forms. The aim of this article is therefore to review the available evidence for CAM in gynaecological oncology practice. The continued need for research is highlighted, as is the need to integrate practices supported by good evidence into conventional gynaecological oncology.

Evaluation of Therapy Management and Patient Compliance in Postmenopausal Patients with Hormone Receptor-positive Breast Cancer Receiving Letrozole Treatment: The EvaluateTM Study.

Introduction: The EvaluateTM study (Evaluation of therapy management and patient compliance in postmenopausal hormone receptor-positive breast cancer patients receiving letrozole treatment) is a prospective, non-interventional study for the assessment of therapy management and compliance in the routine care of postmenopausal women with invasive hormone receptor-positive breast cancer receiving letrozole. The parameters for inclusion in the study are presented and discussed here. Material and Methods: Between January 2008 and December 2009 a total of 5045 patients in 310 study centers were recruited to the EvaluateTM study. Inclusion criteria were hormone receptor-positive breast cancer and adjuvant treatment or metastasis. 373 patients were excluded from the analysis for various reasons. Results: A total of 4420 patients receiving adjuvant treatment and 252 patients with metastasis receiving palliative treatment were included in the study. For 4181 patients receiving adjuvant treatment, treatment with the aromatase inhibitor letrozole commenced immediately after surgery (upfront). Two hundred patients had initially received tamoxifen and started aromatase inhibitor treatment with letrozole at 1-5 years after diagnosis (switch), und 39 patients only commenced letrozole treatment 5-10 years after diagnosis (extended endocrine therapy). Patient and tumor characteristics were within expected ranges, as were comorbidities and concurrent medication. Conclusion: The data from the EvaluateTM study will offer a good overview of therapy management in the routine care of postmenopausal women with hormone receptor-positive breast cancer. Planned analyses will look at therapy compliance and patient satisfaction with how information is conveyed and the contents of the conveyed information.

Channelling optics for high quality imaging of sensory hair.

A long distance microscope (LDM) is extended by a lens and aperture array. This newly formed channelling LDM is superior in high quality, high-speed imaging of large field of views (FOV). It allows imaging the same FOV like a conventional LDM, but at improved magnification. The optical design is evaluated by calculations with the ray tracing code ZEMAX. High-speed imaging of a 2 × 2 mm(2) FOV is realized at 3.000 frames per second and 1 µm per pixel image resolution. In combination with flow sensitive hair the optics forms a wall shear stress sensor. The optics images the direct vicinity of twenty-one flow sensitive hair distributed in a quadratic array. The hair consists of identical micro-pillars that are 20 µm in diameter, 390 µm in length and made from polydimethylsiloxane (PDMS). Sensor validation is conducted in the transition region of a wall jet in air. The wall shear stress is calculated from optically measured micro-pillar tip deflections. 2D wall shear stress distributions are obtained with currently highest spatiotemporal resolution. The footprint of coherent vortical structures far away from the wall is recovered in the Fourier spectrum of wall shear stress fluctuations. High energetic patterns of 2D wall shear stress distributions are identified by proper orthogonal decomposition (POD).

Cranz-Schardin camera with a large working distance for the observation of small scale high-speed flows.

The Cranz-Schardin camera utilizes a Q-switched Nd:YAG laser and four single CCD cameras. Light pulse energy in the range of 25 mJ and pulse duration of about 5 ns is provided by the laser. The laser light is converted to incoherent light by Rhodamine-B fluorescence dye in a cuvette. The laser beam coherence is intentionally broken in order to avoid speckle. Four light fibers collect the fluorescence light and are used for illumination. Different light fiber lengths enable a delay of illumination between consecutive images. The chosen interframe time is 25 ns, corresponding to 40 × 10(6) frames per second. Exemplarily, the camera is applied to observe the bow shock in front of a water jet, propagating in air at supersonic speed. The initial phase of the formation of a jet structure is recorded.

Optimized transformation of the glottal motion into a mechanical model.

During phonation the human vocal folds exhibit a complex self-sustained oscillation which is a result of the transglottic pressure difference, of the characteristics of the tissue of the folds and of the flow in the gap between the vocal folds (Van den Berg J. Myoelastic-aerodynamic theory of voice production. J Speech Hearing Res 1958;1:227-44 [1]). Obviously, extensive experiments cannot be performed in vivo. Therefore, in literature a variety of model experiments that try to replicate the vocal folds kinematics for specific studies within the vocal tract can be found. Here, we present an experimental model to visualize the fluid dynamics which result from the complex motions of real human vocal folds. An existing up-scaled glottal cam model with approximate glottal kinematics is extended to replicate more realistically observed glottal closure types. This extension of the model is a further step in understanding the fluid dynamical mechanisms contributing to the quality of human voice during phonation, in particular the cause (changed glottal kinematics) and its effect (changed aero-acoustic field). For four typical glottal closure types cam geometries of varying profile are generated. Two counter rotating cams covered with a silicone membrane reproduce as well as possible the observed glottal movements.

Experimental flow study of modeled regular and irregular glottal closure types.

The present study shows the results of visualization experiments of the jet formation through a dynamic model of the human vocal folds. The model consists of two counter-rotating, 3D-shaped driven cams covered with a stretched silicone membrane. The 3D contours of the cams are a result of an optimized mapping of observed characteristic clinical vocal fold motions. The experiments are performed by using cams which produce the convex, triangular, rectangular, and concave or sand-glass regular glottis closure types. Two irregular cases are investigated: one of the convex cams is statically closed or opened. These cases cause an oscillating jet which attaches to the ventricular folds and appears to change the part of the aero-acoustic sound spectrum induced by vortices.

Cycle control, tolerability, efficacy and acceptability of the vaginal contraceptive ring, NuvaRing: results of clinical experience in Germany.

OBJECTIVES: To investigate the real-life clinical experience of NuvaRing users in Germany. METHODS: An open-label, prospective, uncontrolled, non-randomized, multicentre postmarketing surveillance study was conducted by 1204 gynaecologists amongst 5823 women requesting contraception. The women underwent routine examinations and contraceptive counselling, and were assessed after three and six cycles of NuvaRing use. RESULTS: Good cycle control was observed and there was a reduction in cycle irregularity and inter-menstrual bleeding, bleeding duration and intensity, and dysmenorrhoea. NuvaRing was well tolerated, and had no significant effect on body weight or blood pressure. Nine women became pregnant unintentionally (two had conceived before they started to use NuvaRing, three due to non-compliance, one because of repeated ring expulsion/loss and three during treatment in spite of having applied this latter as instructed). Most women expressed their satisfaction with NuvaRing; 82% were 'very satisfied/ satisfied', 72% planned to continue using it and 82% would recommend it to others. More than 90% of women found NuvaRing 'without problems/easy' to insert and to remove, and more than 80% of the women and their partners were not disturbed by its presence during intercourse. CONCLUSION: NuvaRing is a highly effective and acceptable method of once-monthly contraception that is safe and well tolerated.

Measurement of induced acrosome reactions in human sperm using physiologic stimuli--relevance for the prediction of fertilization outcome.

Fertilization failure following standard in vitro fertilization in couples with normozoospermic men is an as yet unexplained phenomenon. A wide range of gametic disorders as well as environmental factors might contribute to this pathologic condition. One crucial condition appears to be the inability of the spermatozoa to undergo the acrosome reaction (AR). A discriminative test to distinguish fertile from non-fertile spermatozoa would be of utmost interest. In a prospective study, semen samples from men with normal semen parameters and fertilization failure were compared with semen samples from men with normal semen parameters and normal fertilization as to their capacity to undergo the AR. AR was induced using calcium ionophore as well as the physiologic stimuli progesterone and prostaglandin E(1). Discriminance analyses were undertaken to help identify patients with probable fertilization failure. Our data show that in patients with fertilization failure, the capacity of spermatozoa to undergo induced AR is greatly reduced using both unphysiologic and physiologic stimuli. However, physiologic stimuli are more suitable to identify patients with fertilization failure. Using physiologic stimuli, a formula was established to identify patients likely to fail at fertilization.

Axial flow catheter pump for circulatory support.

AIM: The development of a percutaneously insertable catheter pump for temporary left ventricular and circulatory support in patients with acute ischemic cardiomyopathy. MATERIAL AND METHODS: The expandable axial flow pump (introduction diameter 9-F, expanded diameter 6.5 mm) is mounted at the tip of a catheter, designed to be placed in aortic transvalvular position. Hydrodynamic tests were performed in a static flow model and in a pulsatile mock circuit (Medos VAD, Stolberg, Germany). Cardiogenic shock was simulating in vitro and in vivo. RESULTS: At a rotation speed of 32,000 rpm the catheter pump delivered a maximum flow of more than 4.0 L/min against a systemic mean pressure of 60 mmHg. Under shock simulation the pump significantly improved output and systemic pressure. CONCLUSION: A percutaneously insertable catheter pump is technically feasible. Hydrodynamic efficacy allows sufficient cardiac support under simulated shock condition.

Cytogenetic analysis of giant oocytes and zygotes to assess their relevance for the development of digynic triploidy.

BACKGROUND: In order to assess the role of binucleate giant oocytes for generating digynic triploidy, we studied their frequency, maturation patterns and chromosomal complements at metaphase II (MII) or after fertilization. METHODS: Uncleaved, giant zygotes were incubated with podophyllotoxin and vinblastine, treated with hypotonic solution and fixed by a gradual fixation method. Giant MII oocytes were directly subjected to hypotonic treatment. The chromosomes were stained with Giemsa. RESULTS: A total of 7065 oocytes were collected during the study period, of which 18 (0.26%) were classified as giant cells. When considering only those patients in whom giant cells were identified (among other normal sized cells) a giant cell frequency of 18/237 (7.6%) was found. Nine cells underwent a union of the nuclei during maturation to MII and four of them became fertilized showing two pronuclei. Seven oocytes maintained the binucleate state to MII and one of them was fertilized showing three pronuclei. Ten unfertilized cells were available for cytogenetic analysis and proved to be diploid. All five giant zygotes revealed triploidy. CONCLUSIONS: The data suggest that giant oocytes may play an important, yet underestimated role in causing digynic triploidy. We recommend the exclusion of giant oocytes from IVF trials and that giant cells should be discarded, even if they carry the regular number of two pronuclei.

Sperm acrosome antigen-1. Specific tissue distribution of immunoreactivity in a teleost fish, the swordtail ( Xiphophorus helleri).

The acrosome reaction is a fundamental requirement for mammalian fertilization. Its exact molecular mechanisms and cellular elements are still poorly understood. We have detected an acrosomal sperm antigen, SAA-1, by monoclonal antibodies directed against SAA-1, that appears to be critically involved in the regulation of the acrosome reaction. SAA-1 is conserved within a broad range of mammalian species, emphasizing its important role in mammalian reproduction. Here we demonstrate that SAA-1 is immunohistochemically detectable in a nonmammalian vertebrate whose sperm do not possess an acrosome. In the swordtail, a live-bearing teleost with special reproductive tactics, we were able to demonstrate immunoreactivity of sperm heads of spermatids and mature sperm in the testis using monoclonal antibodies against SAA-1. Due to the cystic spermatogenesis with synchronous sperm maturation, immunoreactive maturational stages could be clearly identified. Stored immunoreactive sperm were also identified in spermathecal tissue of the female genital tract. Interestingly, immunoreactivity was furthermore detected in defined cells of the compounded endocrine organs pituitary and endocrine pancreas. All these different cell systems are involved in paracrine regulation and exhibit exocytotic properties. The possible nature of SAA-1 is discussed. Additionally, some new aspects of the morphologic composition of the swordtail pituitary are described.

The surgical trauma of abdominal wall incision. A comparison of laparoscopic vs open surgery with three-dimensional stereography.

BACKGROUND: Laparoscopic operations seem to respect the integrity of the abdominal wall better than conventional laparotomy, but the effects of surgical trauma are not well understood. The new technique of three-dimensional stereography makes it possible to describe and calculate the mobility of the abdominal wall and the nature of the underlying disturbances. METHODS: Three-dimensional stereography is a noninvasive optical method of measuring surface areas. Abdominal wall mobility can be assessed by comparing changes to the abdominal surface in its minimum and maximum excursions. Different parameters, such as height difference and curvature, are calculated. We studied patients undergoing different types of surgical procedures (laparoscopy and open surgery) by measuring their abdominal wall mobility before and after the procedure. We also compared these patients to a control group. Each group consisted of 30 patients, who were evaluated prospectively. RESULTS: We found a significant difference in abdominal wall mobility between patients treated via a laparoscopic approach, and those who had conventional surgery. At 7 days after laparoscopy, abdominal movement was always the same in the laparoscopic group as in the controls. By contrast, the open surgery group still showed a significant lack of mobility 12 days after the procedure. CONCLUSION: The new method of three-dimensional stereography makes it possible to compare the trauma associated with different surgical approaches as it affects the integrity of the abdominal wall. As compared with open surgery, laparoscopy has a significant positive effect on abdominal wall integrity.

Cytogenetic analysis of human zygotes displaying three pronuclei and one polar body after intracytoplasmic sperm injection.

BACKGROUND: Digynic zygotes with three pronuclei and one polar body obtained after intracytoplasmic sperm injection (ICSI) were studied cytogenetically to elucidate the frequency and origin of chromosomal abnormalities at the earliest stage of conception. METHODS: Uncleaved, single-cell zygotes were incubated with podophyllotoxin and vinblastine and fixed by a gradual fixation air drying method. The chromosomes were stained with Giemsa. RESULTS: Twenty-two (50%) out of 44 informative zygotes revealed cytogenetic alterations, including aneuploidy (six cells, 13.6%), structural aberrations (10 cells, 22.7%) and combinations of numerical and structural abnormalities (two cells, 4.5%). In one case (2.3%), double aneuploidy or an effect of chromosomal translocation could not be distinguished and one zygote (2.3%) turned out tetraploid due to injection of a diploid spermatozoon. Two zygotes (4.5%) showed an irregular chromatid segregation between the two maternal complements. In completely analysable cells, the sex chromosome ratio XXX:XXY was 17:15. CONCLUSIONS: Digynic ICSI zygotes carry a high rate of cytogenetic abnormalities that obviously have been transmitted by the participating oocytes and spermatozoa. We also confirmed the previously reported, possibly ICSI-induced irregular oocyte chromatid segregation. The results suggest that aneuploidy in the oocytes must have been caused by predivision instead of non-disjunction.

Controlled trial with a monthly combination injectable contraceptive in Europe.

In a controlled, multicenter trial conducted in Europe, the safety and efficacy of a monthly injectable combination hormone contraceptive were found to be comparable to those of an oral contraceptive. There were no contraceptive failures in either arm of the trial. The incidence and types of side-effects were similar. The rates of patient satisfaction in the monthly injectable and oral contraceptive arms of the study were also comparable; both exceeded 90%. The results from the European study are consistent with clinical trials conducted elsewhere and support the conclusion that the monthly combination injectable contraceptive represents a desirable new birth control method. Data from the 24-week interim analyses are presented.

Regulation of the synthesis of H2-forming methylenetetrahydromethanopterin dehydrogenase (Hmd) and of HmdII and HmdIII in Methanothermobacter marburgensis.

Recently it was found that the specific activity of H2-forming methylenetetrahydromethanopterin dehydrogenase (Hmd) in Methanothermobacter marburgensis (formerly Methanobacterium thermoautotrophicum strain Marburg) increased six-fold when the hydrogenotrophic archaeon was grown in chemostat culture under nickel-limited conditions. We report here that the increase is due, at least in part, to increased expression of the hmd gene. This was demonstrated by Northern and Western blot analysis. These techniques were also used to show that hmd expression in growing M. marburgensis is not under the control of the H2 concentration. Studies with monoclonal antibodies on the effect of growth conditions on the expression of hmdII and hmdIII, which have been proposed to encode Hmd isoenzymes, were also carried out. The results indicate that the expression of these two genes is regulated by H2 rather than by nickel, and that HmdIII and HmdIII most probably do not exhibit Hmd activity.