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Background Intrauterine adhesions (IUAs) are one of the main reproductive system diseases in women worldwide. Fusion between the injured opposing walls leads to partial-to-complete obliteration of the cavity and/or cervical canal. The main clinical manifestations in case of IUAs are menstrual disturbances, cyclic pain and reproductive disorders. The reproductive outcomes of women with IUAs remain limited and inefficient compared to women without IUAs, even after adhesiolysis. An exact understanding of the underlying mechanisms and processes to explain the compromised reproductive performance and outcomes in case of IUAs are lacking. Methods A systematic literature review of MEDLINE-PubMed (1966 to January 2022) and EMBASE (1974 to January 2022) was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies were included if they reported underlying causes, related mechanisms and processes to explain the association between IUAs and impaired reproductive performance, pregnancy and obstetric complications. Results After an extensive review of the literature, 58 articles were identified reporting underlying mechanisms to explain the association between IUAs and impaired fertility. Intrauterine scarring influences the process of fertilization, reproductive performance and ultimately reproductive outcome. IUAs can disturb the cervico-utero-tubal sperm transport and result in an avascular and unresponsive endometrium with decreased receptivity and thickness. Abnormal decidualization and abnormal trophoblastic infiltration leads to placental attachment disorders. Moreover, the risk for premature delivery, intrauterine fetal growth restriction and fetal anomalies is increased in case of IUAs. Conclusion The impact of IUAs on reproductive performance, even after adhesiolysis, is becoming more apparent. The postulated mechanisms to explain the association are related to sperm transport, embryo implantation and placentation. Prevention, by preserving the basal layer of the endometrium is essential. Effective and evidence-based strategies for the prevention of endometrial injury and formation of IUAs, are urgently needed.

Background: The development of dental caries around orthodontic brackets is a common complication of orthodontic treatment. Objectives: This study aimed to compare the antibacterial efficacy of stainless steel (SS) brackets coated with copper oxide nanoparticles (CuO-NPs), titanium dioxide nanoparticles (TiO2-NPs), and hydroxyapatite silver nanoparticles (HA-SNPs) against Streptococcus mutans. Methods: In this in vitro, experimental study, 20 orthodontic brackets were assigned to four groups (n = 5, each group). One group served as the no-intervention control group, and the brackets in the remaining three groups underwent dip coating with CuO-NPs, TiO2-NPs, and HA-SNPs < 100 nm. The number of S. mutans colonies was counted after 24 h, one week, and one and three months. Data were analyzed using the Shapiro Wilk test, repeated measures ANOVA, and Bonferroni multiple comparisons test. Results: All three experimental groups exhibited similar antibacterial properties after 90 days of trial (P > 0.05). Moreover, CuO-NPs had a greater inhibitory effect than TiO2-NPs on S. mutans after 24 h (P = 0.007). However, the inhibitory effect of HA-SNPs was not significantly different from that of TiO2-NPs (P = 0.259) or CuO-NPs (P = 0.224). Conclusions: Considering the similar antibacterial properties of all three coatings in the long term, all three types of nanoparticles can be used to coat orthodontic brackets to prevent caries. However, due to the high cost and difficult preparation of HA-SNPs and the slightly higher efficacy of CuO-NPs in the short-term, the latter may be preferred for this purpose.

Additional file 1: Additional table 1. Included studies in this review.

Additional file 1: Table 1. Comparisons of group characteristics for participants and excluded children. Proportions, and P-values from a χ2-test.

Background. Tubal patency testing is an essential part of female subfertility evaluation. Traditionally, hysterosalpingography (HSG) was the first step to evaluate tubal patency. However, during the past decade Hysterosalpingo-Contrast Sonography (HyCoSy) was introduced in order to avoid radiation exposure and Hysterosalpingo-Foam Sonography (HyFoSy) has been developed as a safe and less painful alternative. Objectives and Rationale. The aim of this narrative review is to provide an overview of the currently available HyFoSy literature and related clinical aspects. Search Methods. A literature search was conducted using PubMed and Embase from the introduction of HyFoSy to March 2019. Unfortunately, a meta-analysis was not possible due to a too small number of studies, being mutually incomparable for the various subjects of clinical aspects, even for the reliability as a test for tubal patency. Outcomes. Nine small studies concluded that the accuracy and effectiveness as a test for tubal patency of 2D- and 3D-HyFoSy are comparable or even better than HSG or HyCoSy. With or without using Doppler techniques, 3D-HyFoSy does not seem to offer benefits above real-time 2D-HyFoSy. Five studies reported on pain and discomfort during HyFoSy, concluding that HyFoSy is a well-tolerated, less painful procedure compared to HSG, without a need for the use of analgesics. There are suggestions about an increased pregnancy rate in the first three cycles after the procedure but in no studies pregnancy outcome after HyFoSy was compared with other or no intervention. Wider Implications. HyFoSy is a promising and safe alternative for HSG with regard to accuracy and effectiveness. HyFoSy lacks radiation and iodine exposure and is a well-tolerated and less painful procedure than HSG, without the need for analgesics. However more research is needed to make clear statements regarding a therapeutic effect of HyFoSy.

Background. Tubal patency testing is an essential part of female subfertility evaluation. Traditionally, hysterosalpingography (HSG) was the first step to evaluate tubal patency. However, during the past decade Hysterosalpingo-Contrast Sonography (HyCoSy) was introduced in order to avoid radiation exposure and Hysterosalpingo-Foam Sonography (HyFoSy) has been developed as a safe and less painful alternative. Objectives and Rationale. The aim of this narrative review is to provide an overview of the currently available HyFoSy literature and related clinical aspects. Search Methods. A literature search was conducted using PubMed and Embase from the introduction of HyFoSy to March 2019. Unfortunately, a meta-analysis was not possible due to a too small number of studies, being mutually incomparable for the various subjects of clinical aspects, even for the reliability as a test for tubal patency. Outcomes. Nine small studies concluded that the accuracy and effectiveness as a test for tubal patency of 2D- and 3D-HyFoSy are comparable or even better than HSG or HyCoSy. With or without using Doppler techniques, 3D-HyFoSy does not seem to offer benefits above real-time 2D-HyFoSy. Five studies reported on pain and discomfort during HyFoSy, concluding that HyFoSy is a well-tolerated, less painful procedure compared to HSG, without a need for the use of analgesics. There are suggestions about an increased pregnancy rate in the first three cycles after the procedure but in no studies pregnancy outcome after HyFoSy was compared with other or no intervention. Wider Implications. HyFoSy is a promising and safe alternative for HSG with regard to accuracy and effectiveness. HyFoSy lacks radiation and iodine exposure and is a well-tolerated and less painful procedure than HSG, without the need for analgesics. However more research is needed to make clear statements regarding a therapeutic effect of HyFoSy.

Hysterectomy is the most frequently performed major surgical intervention in gynecology. Although surgically removing the uterus is invasive, it represents the most definitive treatment option for heavy menstrual bleeding. In this article, we will discuss the indications for hysterectomy as a treatment for heavy menstrual bleeding, the different approaches to perform the hysterectomy, the complications which may occur during and after this procedure and finally the outcomes in comparison with other treatment options.

This was a retrospective review of all pregnancies reported after Essure in situ in the Netherlands. Pregnancies included those that were unintentional (resulting from lack of protocol adherence and/or misread confirmation tests) and those that were intentional (resulting from off-label use of Essure micro-inserts for hydrosalpinx closure before in vitro fertilization/intracytoplasmic sperm injection with embryo transfer or in vitro fertilization with embryo transfer after regret of sterilization). The outcomes of 50 pregnancies in women with 1 or 2 micro-inserts in situ were evaluated. Eight unintended pregnancies and 18 intended pregnancies resulted in birth of a full-term healthy baby. Seven infants were delivered via cesarean-section. Two women delivered prematurely by C-section, (singleton after 34 weeks 1 day, twins after 35 weeks 3 days). All babies are healthy and without any congenital anomalies. There were 2 stillbirths after 20 weeks; however, it is unlikely that this was related to the presence of the micro-inserts. In conclusion, it is unlikely that the presence of intratubal micro-inserts interferes with implantation and the developing amniotic sac and fetus.

Objective To investigate the success rate of proximal tubal occlusion with Essure® devices in subfertile women with unilateral or bilateral hydrosalpinx and to observe the results of subsequent treatment with IVF-ET and/or frozen embryo transfer. Study design Prospective, single-arm, clinical study in 20 women with unilateral or bilateral hydrosalpinges (all visible on transvaginal ultrasound) due to undergo IVF-ET and/or frozen embryo transfer. In all patients, laparoscopy was considered to be contraindicated due to extensive pelvic adhesions. Result(s) In all patients the Essure® devices were placed in an ambulant setting without any complications. Proximal tubal occlusion was confirmed by hysterosalpingography in 19 out of 20 patients (95%) and in 26 of 27 treated tubes (96%). After 45 embryo transfer procedures in 19 patients, 18 pregnancies with 12 live births, 6 miscarriages and 1 immature delivery (probably related to cervical insufficiency leading to chorioamnionitis and subsequent rupture of the membranes) were observed. Conclusion(s) Essure® devices are effective in inducing proximal tubal occlusion in subfertile patients with hydrosalpinges. After artificial reproductive treatments a cumulative live birth rate per patient of 63% and a cumulative live birth rate per transfer of 27% were achieved. The latter was related to the large proportion of patients with severe endometriosis.

Background This study was conducted to describe the first experiences with hysterosalpingo-foam sonography (HyFoSy) as a first step routine office procedure for tubal patency testing. Methods A prospective observational cohort study was started in a university affiliated teaching hospital. In 2010, 73 patients with subfertility and a low risk of tubal pathology were examined. A non-toxic foam containing hydroxymethylcellulose and glycerol was applicated through a cervical applicator for contrast sonography (HyFoSy). Tubal patency was determined by transvaginal ultrasonographic demonstration of echogenic dispersion of foam in the Fallopian tube and/or the peritoneal cavity. Only in case patency could not be demonstrated, a hysterosalpingography (HSG) was performed as a control. Results In 67 out of 73 (92%) patients, a successful procedure was performed. In 57 out of 73 (78%) cases, there was no further need for a HSG. In five patients (5/73; 7%) tubal occlusion was confirmed by HSG and in five patients (5/73; 7%) there was discordance between HyFoSy and HSG. Of 73 patients, 14 (19%) conceived within a median of 3 months after the procedure. Conclusions HyFoSy is a successful procedure to demonstrate tubal patency as a first step office procedure.

Objective To investigate the success rate of proximal tubal occlusion with Essure devices in subfertile women with hydrosalpinges, and to observe the results of subsequent treatment with IVF. Design Prospective, single-arm, clinical study. Setting University hospital and teaching hospital. Patient(s) Ten women with uni- or bilateral hydrosalpinges prior to IVF. In all patients laparoscopy was felt to be contraindicated. Intervention(s) Hysteroscopic placement of Essure devices in an office setting. Main Outcome Measure(s) Placement rate, successful proximal tubal occlusion, and pregnancy rate after IVF. Result(s) All patients had successful placement of the Essure devices without any complications. Proximal tubal occlusion was confirmed by hysterosalpingography in 9 out of 10 patients. A 40% ongoing pregnancy rate was achieved with 20% life births after one IVF cycle and/or frozen embryo transfer. Conclusion(s) Proximal occlusion of hydrosalpinges with Essure devices before IVF is a successful treatment for patients with a contraindication for salpingectomy.

This study assessed the efficacy of hysteroscopic polyp removal in the management of abnormal uterine bleeding (AUB) of premenopausal patients. The monthly menstrual blood loss, measured semi-objectively by the pictorial blood loss assessment chart (PBAC) and patients satisfaction were recorded prospectively preoperatively and postoperatively. Twenty-one patients were included. Median monthly PBAC-score before treatment was 288 (range 142-670) and 6 months after polyp removal 155 (range 39-560). It was concluded that hysteroscopic polyp removal in premenopausal women with AUB reduces the monthly blood loss significantly and has a high satisfaction rate on the short term.

The purpose of this randomized controlled study was to compare conventional resectoscopy and hysteroscopic morcellation among residents in training (Canadian Task Force classification I). Sixty women with an intrauterine polyp or myoma were randomized to either hysteroscopic removal by conventional resectoscopy or hysteroscopic morcellation performed by 6 residents in training for obstetrics and gynecology (10 procedures per resident). The mean operating time for resectosocpy and morcellation was 17.0 (95% confidence interval [95% CI] 14.1-17.9, standard deviation [SD] 8.4) and 10.6 (95% CI 7.3-14.0, SD 9.5) min, respectively (p = .008). Multiple linear regression analysis showed that operating time increased significantly, for both resectoscopy and morcellator, when volume of intrauterine disorder increased. The use of the hysteroscopic morcellator reduced operating time more than 8 min in comparison to conventional resectoscopy (p < .001) when correction for volume was applied. Subjective surgeon and trainer scores for convenience of technique on a visual analog scale were in favor of the morcellator. No learning curve was observed. In conclusion, the hysteroscopic morcellator for removal of intrauterine polyps and myomas offers a good alternative to conventional resectoscopy for residents in training.

Objective A practical attempt to simplify and improve the technique of artificial uterine cavity distension by instilling gel instead of flushing saline. Design Prospective observational study. Setting Teaching hospital. Patient(s) One hundred twenty patients with an indication for sonohysterography (abnormal uterine bleeding, exclusion of congenital abnormalities, or preoperative or postoperative evaluation of submucous myomas, polyps, or synechiae). Intervention(s) A hydroxyethylcellulose gel containing anesthetic and antiseptic agents was instilled in the uterine cavity through a plastic intrauterine insemination cannula attached to a flexible plastic tube and a syringe. Transvaginal (3-dimensional) ultrasonography was performed concomitantly. Main Outcome Measure(s) Stable filling of the uterine cavity allowing a high-quality ultrasonographic visualization. Result(s) An optimal distension of the uterine cavity could be achieved with an average of only 4 mL (range, 2–10 mL) in 113 patients. As expected, a stable filling of the uterine cavity permitted a precise visualization of the uterine cavity and its linings and offered an optimal presentation for a 3-dimensional ultrasound recording and reconstruction. Conclusion(s) Gel instillation is a simple technique with minimal inconvenience for the patient and seems to be an attractive alternative to saline infusion during sonohysterography.

Fibroids or (leio)myomas are benign tumours that very commonly derive from smooth muscle cells of the myometrium. They are the most common indication for a hysterectomy. However, in women desirous of preservation of their uterus or of their fertility, a myomectomy may be a more appropriate form of surgical therapy. The submucous variant is often associated with heavy menstrual bleeding or subfertility. It can be removed with hysteroscopic surgery. Refinements of hysteroscopic surgical techniques have resulted in a better ability to remove submucous myomas. The state of the art of such hysteroscopical techniques and instrumentation to treat submucous myomas and what has been proven is discussed.

In this observational study, we analysed whether a period of wait and see was reasonable following incomplete removal of submucous fibroids, with regard to symptoms of abnormal uterine bleeding, and whether factors predicting subsequent surgery could be identified.In 3 affiliated hospitals, patients with incomplete removal of submucous fibroids, treated with hysteroscopic myomectomy for abnormal uterine bleeding, between January 1997 and January 2005, were followed over time. Using life-table analysis (Kaplan-Meier method), the cumulative proportion of women having surgery-free survival following incomplete removal of submucous fibroids was calculated. Cox-proportional hazard analyses were used to analyse relationships of variables with recurrence of symptoms.Forty-one consecutive patients met the inclusion criteria, and were followed over time. The mean age was 42.5 years (range 27-55). The majority of patients with incomplete removal of submucous fibroids were diagnosed with type 2 fibroids. Termination of the procedure before complete removal was achieved, was principally caused by reaching the maximum fluid deficit (90.2%). The surgery-free percentages were 70.2% (95%-CI: 55.3-85.1) at 1 year, 54.8% (95%-CI: 38.1-70.7) at 2 years, and 44.2% (95%-CI: 26.9-61.5) at 3 years. Size of fibroid (diameter) pre-operatively turned out to be of statistically significant influence, with a hazard ratio of 1.762 (95%-CI: 1.114-2.787) per cm increase in diameter (p=0.016).The results indicate that incomplete removal does not always seem to necessitate subsequent surgery. Instead of subsequent surgery immediately post-operatively, a wait and see policy is worth considering after incomplete removal.

Study objective A new hysteroscopic operating technique was compared retrospectively with conventional resectoscopy. Design Retrospective comparison (Canadian Task Force Classification II-2). Setting Gynecology department of a university-affiliated teaching hospital. Patients Fifty-five women, 27 with endometrial polyps and 28 with submucous myomas. Intervention Patients were treated with a prototype of the Intra Uterine Morcellator (IUM). This cutting device, 35 cm in length, was inserted into a straight working channel of a 90-mm hysteroscope. Measurements and main results The major advantages were ease of removal of tissue fragments through the instrument and the use of saline solution instead of electrolyte-free solutions used in monopolar high-frequency resectoscopy. The mean operating time was 8.7 minutes (95% CI: 7.3–10.1) for the removal of endometrial polyps compared with 30.9 minutes (CI: 27.0–34.8) for resectoscopy, and 16.4 minutes (CI: 12.6–20.2) for submucous myomas compared with 42.2 minutes (CI: 39.7–44.7) for resectoscopy. All procedures were uneventful. Conclusion This new technique is faster, and it appears to be easier to perform. Therefore, it can be expected to result in fewer fluid-related complications and to lead to a shorter learning curve when compared with conventional resectoscopy.

Objective: To examine whether intrauterine application of auto-crosslinked hyaluronic acid (ACP) gel, after dilatation and curettage (D&C), reduces the incidence of intrauterine adhesions (IUAs). Design: Multicenter; women and assessors blinded prospective randomized trial. Setting: University and university-affiliated teaching hospitals. Patient(s): A total of 152 women with a miscarriage of

A state-of-the-art overview of the safety and side-effects of ExEm-gel for uterine cavity distension and ExEm-foam for tubal patency testing is presented. A literature search was carried out using PubMed, textbooks, pharmaceutical databases and reports of toxicity tests. Information on clinical use in humans and experiments in animal models was collected and grouped according to the following components: glycerol, hydroxyethyl cellulose and purified water; subjects included toxicity test, influence on sperm cells, oocytes, blastocyst development, uterine cavity distension, tubal patency testing, pain and obstetric applications. No unknown side-effects of gel or foam, or unexpected concerns about safety, were reported. More information than expected was available on the absence of effects of the components on various human tissues. Although it is difficult to prove that the search is complete, and it is possible that side-effects remain unreported, the combination of glycerol, hydroxyethyl cellulose and purified water is considered to be safe for intrauterine application and tubal patency testing, indicating an optimal risk-benefit ratio in clinical use. The safest strategy, however, is to restrict clinical examinations with gel and foam to the pre-ovulatory phase of the menstrual cycle. (C) 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Objective: To analyze the efficacy of transcervical resection of submucous myomas and to identify prognostic factors for long-term results. Methods: Two-hundred eighty-five women were treated with transcervical resection of submucous myomas without endometrial ablation. In case of incomplete resection a repeat procedure was offered. Long-term follow-up was obtained. Recurrence was defined as the need for further surgery. The relation of several variables with the outcome was analyzed using Cox proportional hazard regression analysis. Results: Seventeen cases (6%) were lost to follow-up. The median follow-up was 46 months (range 1–104 months); for cases without recurrence median follow-up was 42 months (range 16–104 months). Forty-one (14.5%) patients had repeat surgery. An independent prognostic value of uterine size (P < .001) and number of submucous myomas (P < .001) for recurrence was noted. Twenty of 41 patients who had repeat surgery subsequently had a hysterectomy. None of the variables investigated predicted the need for hysterectomy. The surgery-free percentage of 165 patients with normal sized uteri and not more than two myomas was 94.3% (standard error ± 1.8%) at 2 years and 90.3% (± 3.0%) at 5 years. Conclusion: Transcervical resection of submucous myomas is a safe and effective treatment for patients with a normal sized uterus and not more than two myomas. It is an acceptable alternative for selected other patients. The need for a combined endometrial ablation is questionable. Transcervical resection of submucous myomas will give patients a high chance of averting further surgery and should modify the way patients are counseled.

OBJECTIVE: We determined the diagnostic vaue of transvaginal ultrasonography for endometrial and intrauterine abnormalities in patients with abnormal uterine bleeding. STUDY DESIGN: Between June 1, 1992, and June 1, 1993, 279 consecutive patients underwent transvaginal ultrasonography. Findings were compared with the final diagnosis established by diagnostic hysteroscopy and histologic examination. RESULTS: Transvaginal ultrasonography demonstrated a sensitivity of 0.96 and a specificity of 0.89. With a pretest probability (prevalence) of 0.42, this resulted in posttest probabilities of 0.03 in the case of a normal sonogram and 0.87 for an abnormal sonogram. The corresponding likelihood ratios were 0.04 and 9.09, respectively. CONCLUSION: Transvaginal ultrasonography seems to be an effective procedure to exclude endometrial and intrauterine abnormalities. Its use could be implemented as a routine first-step procedure in patients with abnormal uterine bleeding, and it selects those in need of further diagnostic evaluation in the case of an abnormal or inconclusive sonogram

γ- and β-Amino acids have been used previously to inactivate γ-aminobutyric acid aminotransferase. Here it is shown that β-halo-, β-phospho-, β-sulpho- L -alanine, and vinyl- L -glycine, all α-amino acids, are time dependent inactivators of purified γ-aminobutyrate aminotransferase. Observations that this inactivation is stereospecific and requires the formation of a Michaelis complex support a catalytic mechanism for this process. α-Amino acids are time dependent inactivators of purified γ-aminobutyrate aminotransferase.

A structural similarity of several monobactams (2–4), 3-aminonocardicinic acid (6), 6-aminopenicillanic acid (7), 7-aminocephalosporanic acid (8), and 7-aminodesacetoxycephalosporanic acids (9, 10) to γ-aminobutyric acid (GABA) and to known inhibitors and substrates of GABA aminotransferase is described. Because of this, the above-mentioned compounds were tested as competitive inhibitors and as inactivators of pig brain GABA aminotransferase. All of the compounds were competitive inhibitors of GABA aminotransferase. On the basis of the inhibitory potency of these conformationally-rigid GABA analogues it is hypothesized that GABA is bound at the active site with its amino and carboxylate groups in a syn orientation. None of the compounds inactivates GABA aminotransferase. These β-lactam analogues represent the first examples of a new class of inhibitors of GABA aminotransferase.

To examine the relationship between surgical volume and complications and resource utilization for myomectomy.This retrospective cross-sectional study in a university hospital setting (Brigham and Women's Hospital) analyzed 527 consecutive women with uterine fibroids who underwent abdominal myomectomy. A multivariate analysis was performed to determine the association between surgical volume and outcomes.There were no significant medical or surgical complications following myomectomy. However, high-volume surgeons did procedures significantly faster, they collected more tissue per time and their patients had less blood loss.The surgical volume of the physician does not affect the safety of abdominal myomectomy. However, high-volume surgeons had more efficient resource utilization than did physicians doing fewer cases.

Objective To study the success rate of hysteroscopic adhesiolysis and the spontaneous recurrence rate of intrauterine adhesions (IUAs) in patients with Asherman syndrome. Design Cohort study. Setting University-affiliated hospitals. Patient(s) A total of 638 women with Asherman syndrome were included, all diagnosed using hysteroscopy, and operated on between 2003 and 2013. Intervention(s) Hysteroscopic adhesiolysis. Main Outcome Measure(s) Hysteroscopic adhesiolysis was classified as successful if a normalization of menstrual blood flow occurred, along with a restored, healthy, cavity anatomy, free of adhesions, with hysteroscopic visualization of ≥1 tubal ostium. Recurrences of adhesions were diagnosed using hysteroscopy after an initial successful procedure. Result(s) A first-trimester procedure preceded Asherman syndrome in 371 women (58.2%) and caused adhesions of grades 1–2A. In 243 (38.1%) women, a postpartum procedure caused IUAs of grades 3–5. The procedure was successful in 606 women (95%), and restoration of menstrual blood flow occurred in 97.8%; IUAs spontaneously recurred in 174 (27.3%) of these cases. High grades of adhesions were predictive of a higher chance of spontaneous recurrence of adhesions. Conclusion(s) In 95% of women with Asherman syndrome, a healthy uterine cavity was restored with hysteroscopic adhesiolysis, in 1–3 attempts, with a 28.7% recurrence rate of spontaneous IUAs.

Considerable advances have been made in the knowledge regarding fracture healing and treatment duringrecent decades. Nevertheless, in 5-10 per cent of fractures, there are healing complications leading to complextreatment conditions, discomfort for patients and considerable costs. Therefore, there is a need for furtheradvances in the understanding of fracture healing. Several clinically relevant animal models have been usedto study the biological mechanisms of the bone tissue repair process during fracture healing. However, informationregarding reproducibility of such models is limited, which makes comparison of studies difficult.AIMS: To develop a reproducible and clinically relevant experimental fracture model in rat. To investigatehow fracture environment and fracture fixation stability influence the temporal distribution of ossificationin experimental fractures in this model. To investigate the possible influence of fracture environment andfracture fixation stability as well as the temporal distribution of ossification on biomechanical stability duringfracture healing.To study neovascularization during ossification in healing fractures.METHODS: A reliable and reproducible method for experimental external fixation of long bones in rats wasdeveloped.The ossification in external fixated femur osteotomies was studied with biomechanical, histological,histomorphometrical, immunohistochemical, microfil perfusion and transmission electron microscopy methods.RESULTS AND CONCLUSIONS: The method for experimental external fixation of long bones in rats wasfound to be reliable and reproducible for investigations of bone repair. In the early phase of fracture healing,periosteal ossification and intramedullary ossification were found to be histologically similar and were notinfluenced by fracture fixation rigidity or fracture environment. The intramedullary ossification was foundto be of considerable magnitude if tissues associated with the intramedullary region were preserved duringfracture fixation.Woven bone might be a prerequisite for the differentiation process of endochondral ossification.The magnitude of chondroid tissue is suggested to be of importance for the biomechnical stability inhealing fractures. Delayed fracture healing may possibly induce systemic stimulation of bone mass.There was considerable similarity between the neovascularization during endochondral ossification inepiphyseal growth plates and experimental fracture healing. The results strongly support the concept thatendochondral ossification during fracture healing is a recapitulation of endochondral ossification duringembryonic development of long bones.

To determine the predictive value of dilatation and curettage (D&C) for diagnosing intrauterine disorders in patients with persistent abnormal uterine bleeding. An observational descriptive study was performed in a large university-affiliated teaching hospital. The suspicion of intrauterine disorders described in theater-reports involving D&C was compared with the hysteroscopical findings in 131 premenopausal patients with persistent complaints of abnormal uterine bleeding who were referred by other gynecologists within six months after D&C. Pre-test probability (prevalence), post-test probabilities (predictive values) and likelihood-ratio's were calculated. The pre-test probability for all intrauterine disorders was 0.49. The post-test probabilities for a 'suspect' and a 'not suspect' D&C were 0.61 and 0.46 respectively with an overlap of confidence-intervals. The corresponding likelihood-ratio's were 1.69 and 0.87 respectively. D&C findings were of no value in the prediction of the presence or absence of intrauterine disorders in this population with persistent complaints

Objective: To determine the contribution of several variables to fluid loss during transcervical resection of submucous myomas. Design: An observational study using multiple linear regression analyses. Setting: A university-affiliated training hospital and a university department of clinical epidemiology and biostatistics. Patient(s): Patients with submucous myomas. Intervention(s): Transcervical resection of submucous myomas and monitoring of fluid loss. Main Outcome Measure(s): Patient age, uterine enlargement, treatment with GnRH analogues or 8-ornithine-vasopressin, type of anesthesia, number of myomas, intramural extension of the myoma (type of myoma), and operating time were tested as variables. Result(s): Only intramural extension of the myoma and operating time were obviously related to fluid loss. For the other variables, such a relation was weak at best. The relation between fluid loss and operating time was not modified by any of the other variables. Conclusion(s): Because fluid loss is an important limiting factor in the transcervical resection of submucous myomas, special attention should be paid to reduction of the operating time and preoperative assessment of the intramural extension of the myoma to guide appropriate patient selection.

gamma-Aminobutyric acid (GABA) aminotransferase is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that catalyzes the conversion of GABA into succinic semialdehyde. Hydrazine analogues have long been known to act as inactivators of PLP-dependent enzymes, including GABA aminotransferase, however, no studies of the molecular mechanism of inactivation of PLP-dependent enzymes by hydrazines have been reported. 3-Hydroxybenzylhydrazine is shown to be a potent in vitro time-dependent inhibitor of pig brain GABA aminotransferase. UV-visible and 1H NMR studies, both with GABA aminotransferase and with PLP as a chemical model for the enzyme-catalyzed reaction, indicate that 3-hydroxybenzylhydrazine reacts both enzymatically and nonenzymatically to form the 3-hydroxybenzylhydrazone of PLP without tautomerization.