Transposable elements contribute to the establishment of the glycine shuttle in Brassicaceae species.

C3 -C4 intermediate photosynthesis has evolved at least five times convergently in the Brassicaceae, despite this family lacking bona fide C4 species. The establishment of this carbon concentrating mechanism is known to require a complex suite of ultrastructural modifications, as well as changes in spatial expression patterns, which are both thought to be underpinned by a reconfiguration of existing gene-regulatory networks. However, to date, the mechanisms which underpin the reconfiguration of these gene networks are largely unknown. In this study, we used a pan-genomic association approach to identify genomic features that could confer differential gene expression towards the C3 -C4 intermediate state by analysing eight C3 species and seven C3 -C4 species from five independent origins in the Brassicaceae. We found a strong correlation between transposable element (TE) insertions in cis-regulatory regions and C3 -C4 intermediacy. Specifically, our study revealed 113 gene models in which the presence of a TE within a gene correlates with C3 -C4 intermediate photosynthesis. In this set, genes involved in the photorespiratory glycine shuttle are enriched, including the glycine decarboxylase P-protein whose expression domain undergoes a spatial shift during the transition to C3 -C4 photosynthesis. When further interrogating this gene, we discovered independent TE insertions in its upstream region which we conclude to be responsible for causing the spatial shift in GLDP1 gene expression. Our findings hint at a pivotal role of TEs in the evolution of C3 -C4 intermediacy, especially in mediating differential spatial gene expression.

[Chorioretinal atrophy in pediatric cerebral folate deficiency-a preventable disease?] / Chorioretinale Atrophie bei kindlichem zerebralem Folatmangel ­ eine vermeidbare Erkrankung?

Cerebral folate deficiency (CFD) results in neurological alterations and a massive degeneration of the choroid/retina if left untreated, which limit the visual field and visual acuity. This article reports the case of a female patient with CFD, who developed autistic personal characteristics prior to reaching school age and first started to speak at the age of 3 years. At the age of 6 years she was presented because of unclear reduced visual acuity in the right eye. At that time mild bilateral peripheral chorioretinal atrophy was present, which subsequently became more pronounced. Additionally, a centrally emphasized chorioretinal atrophy further developed. Visual acuity of both eyes progressively deteriorated until stagnating at 0.1 at the age of 14 years. The causal assignment of the findings of the patient was not possible for many years. Choroideremia was excluded by molecular genetic testing (CHM gene with no mutations) and gyrate atrophy was ruled out by a normal ornithine level. The existence of a mitochondrial disease was almost completely excluded by exome sequencing. After the onset of further nonocular symptoms, e.g. neuromuscular disorders, electroencephalograph (EEG) alterations and autistic disorder, intensified laboratory diagnostics were performed in the treating pediatric hospital. Finally, an extremely low level of the folic acid metabolite 5­methyltetrahydrofolate was detected in the cerebrospinal fluid (CSF) leading to the diagnosis of CFD. High-dose substitution treatment with folic acid was subsequently initiated. After excluding the presence of a pathogenic mutation of the FOLR1 gene for the cerebral folate receptor 1, a high titer blocking autoantibody against cerebral folate receptor 1 was detected as the cause.

[Treatment of myofascial lumbar dorsal pain. Effective clinical diagnostics and therapy]. / Die Behandlung myofaszialer lumbaler Rückenschmerzen. Effektive Diagnostik und Therapie.

BACKROUND: Lumbar dorsal pain is a problem that must be taken seriously and is part of many people's everyday lives. Not only does it cause high costs for the health system, it also frequently leads to inability to work. The significance of the myofascial system is still not taken seriously enough in therapy and clinical diagnostics, when treating dorsal pain. In the following article, the effectiveness of specifically targeted therapy for myofascial pain is evaluated. METHODS: Included in the study were 44 patients referred for lumbar dorsal treatment-resistant pain to a practice specializing in pain therapy. Therapy focused on treatment of the affected muscle area with physiotherapy and the additional techniques of infiltrating trigger points, neural therapy, and general relaxation exercises. Medication was optimized according to the specific guidelines for the condition. The effect of therapy was evaluated using the German pain questionnaire (Deutsche Schmerzfragebogen). RESULTS: After the therapy phase, patients had a significantly lower intensity of pain, anxiety, and depression, as well as an increased quality of life. CONCLUSION: The results indicate that targeted treatment of muscles and fascia in patients with chronic back pain can lead to a reduction of pain symptoms. The consideration of the myofascial systems, particularly in relation to nonspecific back pain, could contribute to improving the treatment of pain and contribute to lowering costs.

[Manual-medical differential diagnosis of low back pain including osteopathic procedures]. / Differenzialdiagnostik manualmedizinischer Syndrome bei unteren Rückenschmerzen unter Einbeziehung osteopathischer Verfahren.

The differential diagnostic evaluation of painful functional disorders of the lumbosacral and lumbopelvic region, i. e. the so-called "low back pain" is very extensive, but is often reduced to the question of chronicity. The manual medical diagnosis can make a valuable contribution in such cases for determination of structural and functional pathology. Early application of manual medical therapies seems to be effective for peracute complaints. The mobilization of restrictions of the pelvic visceral attachments should be included. In the following review manual medical syndromes are presented that summarize the findings from the musculoskeletal and visceral system. This is intended to facilitate the primary differential diagnostic evaluation, as well as treatment planning. The combination with osteopathic methods is very profitable. A necessary specialist differential diagnosis remains essential.

High field FMRI reveals thalamocortical integration of segregated cognitive and emotional processing in mediodorsal and intralaminar thalamic nuclei.

Thalamocortical loops, connecting functionally segregated, higher order cortical regions, and basal ganglia, have been proposed not only for well described motor and sensory regions, but also for limbic and prefrontal areas relevant for affective and cognitive processes. These functions are, however, more specific to humans, rendering most invasive neuroanatomical approaches impossible and interspecies translations difficult. In contrast, non-invasive imaging of functional neuroanatomy using fMRI allows for the development of elaborate task paradigms capable of testing the specific functionalities proposed for these circuits. Until recently, spatial resolution largely limited the anatomical definition of functional clusters at the level of distinct thalamic nuclei. Since their anatomical distinction seems crucial not only for the segregation of cognitive and limbic loops but also for the detection of their functional interaction during cognitive-emotional integration, we applied high resolution fMRI on 7 Tesla. Using an event-related design, we could isolate thalamic effects for preceding attention as well as experience of erotic stimuli. We could demonstrate specific thalamic effects of general emotional arousal in mediodorsal nucleus and effects specific to preceding attention and expectancy in intralaminar centromedian/parafascicular complex. These thalamic effects were paralleled by specific coactivations in the head of caudate nucleus as well as segregated portions of rostral or caudal cingulate cortex and anterior insula supporting distinct thalamo-striato-cortical loops. In addition to predescribed effects of sexual arousal in hypothalamus and ventral striatum, high resolution fMRI could extent this network to paraventricular thalamus encompassing laterodorsal and parataenial nuclei. We could lend evidence to segregated subcortical loops which integrate cognitive and emotional aspects of basic human behavior such as sexual processing.

Deep brain stimulation of globus pallidus internus in a 16-year-old boy with severe tourette syndrome and mental retardation.

A 16- year-old boy with long-standing severe Tourette syndrome (TS) and mental retardation, non-responsive to complex pharmocological and behavioural treatment was selected for bilateral deep brain stimulation (DBS) of the globus pallidus internus (GPi). Pre-operative and post-operative Yale Tourette syndrome scale (YTSS) scores and several other scores were used to quantify the effect of DBS up to one year follow-up. Although subscores of the YTSS improved, the overall outcome of chronic GPi-DBS showed no substantial therapeutic effect. This finding is in contrast to markedly improved TS of the only two adolescent TS patients in whom DBS has been performed so far. In this article we discuss possible reasons for the poor therapeutic effect of GPi-DBS in our patient contributing to the on-going debate on DBS inclusion criteria for adolescent TS patients.

[Legal aspects of hyperkinetic disorders/ADHD]. / HKS/ADHS und rechtliche Aspekte.

With a prevalence of 2-6%, hyperkinetic disorders (F 90, ICD-10) and disturbances of activity and attention (F 90.0, ADHD, ICD-10) are among the psychiatric disorders most commonly diagnosed in children, adolescents, and adults. Children and adolescents diagnosed with ADHD suffer from hyperactivity and deficits in attention and impulse control. Adults usually have problems focusing on one goal, maintaining their attention, modulating emotions effectively, structuring their tasks, and controlling impulses and in executive functions. Legal implications derive from core symptoms and from treatment with stimulants governed by legislation on narcotics. This paper discusses juridical aspects of ADHD in connection with the administration of medication at school, trips abroad within and outside the Schengen area, driving, competitive sports, military service, the increased risk of delinquency, the individual capacity to incur criminal responsibility, developmental criteria for the ability to act responsibly, and modalities for withdrawal treatment or treatment during detention.

Modulation of transcallosally mediated motor inhibition in children with attention deficit hyperactivity disorder (ADHD) by medication with methylphenidate (MPH).

Motor hyperactivity is one of the most outstanding symptoms of attention deficit hyperactivity disorder (ADHD) which might be caused by a disturbed inhibitory motor control. Using focal transcranial magnetic stimulation (TMS) we tested the cortico-callosal inhibition (duration and latency of the ipsilateral Silent Period, iSP) in 23 children with ADHD (mean age 11+/-2.6 years) before and on treatment with methylphenidate (MPH). iSP latency was age correlated, whereas iSP duration as well as Conners scores were age independent. Analyses of mean differences revealed a significant prolongation of iSP duration (p=0.001), shortening of iSP latency (p=0.027) and reduction of Conners score (p=0.001) under medication. Increase of iSP duration and reduction of Conners score under medication were significantly correlated (t=-9.87, p=0.016). Reduced iSP duration and prolonged iSP latency in ADHD children could be the result of a disturbed transcallosally mediated inhibition, most probable due to a combination of maturation deficits of callosal fiber tracts as well as neuronal synaptical transmission within the neuronal network between ipsilaterally stimulated cortex layer III--the origin of transcallosal motor-cortical fibers--and contralateral layer V, the origin of the pyramidal tract. MPH may indirectly improve the dysbalance between excitatory and inhibitory interneuronal activities of this neuronal network via dopaminergic modulatory effects of the striato-thalamo-cortical loop.

MR-guided intervention in women with a family history of breast cancer.

OBJECTIVE: A study was undertaken to assess the clinical value of magnetic resonance (MR) imaging-guided interventions in women with a family history, but no personal history of breast cancer. METHODS AND PATIENTS: Retrospective review was performed on 63 consecutive women who had a family history, but no personal history of breast cancer. A total of 97 lesions were referred for an MR-guided intervention. Standardized MR examinations (1.0 T, T1-weighted 3D FLASH, 0.15 mmolGd-DTPA/kg body weight, prone position) were performed using a dedicated system which allows vacuum assisted breast biopsy or wire localization. RESULTS: Histologic findings in 87 procedures revealed 9 (10%) invasive carcinomas, 12 (14%) ductal carcinomas in situ, 2 atypical ductal hyperplasias (2.5%) and 2 atypical lobular hyperplasias (2.5%). Sixty-two (71%) benign histologic results are verified by an MR-guided intervention, retrospective correlation of imaging and histology and by subsequent follow-up. In ten lesions the indication dropped since the enhancing lesion was no longer visible. Absent enhancement was confirmed by short-term re-imaging of the noncompressed breast and by follow-up. CONCLUSION: Malignancy was found in 24%, high-risk lesions in 5% of successfully performed MR-guided biopsy procedures. A 57% of MR-detected malignancies were ductal carcinoma in situ. In 10% of the lesions the intervention was not performed, since no enhancing lesion could be reproduced at the date of anticipated intervention. Such problems may be avoided if the initial MRI is performed in the appropriate phase of the menstrual cycle and without hormonal replacement therapy.

Regulation of functional steroid receptors and ligand-induced responses in telomerase-immortalized human endometrial epithelial cells.

Information on the regulation of steroid hormone receptors and their distinct functions within the human endometrial epithelium is largely unavailable. We have immortalized human primary endometrial epithelial cells (EECs) isolated from a normal proliferative phase endometrium by stably transfecting the catalytic subunit (hTERT) of the human telomerase complex and cultured these hTERT-EECs now for over 350 population doublings. Active hTERT was detected in hTERT-EECs employing the telomerase repeat amplification assay protocol. hTERT-EECs revealed a polarized, non-invasive epithelial phenotype with apical microvilli and production of a basal lamina when grown on a three-dimensional collagen-fibroblast lattice. Employing atomic force microscopy, living hTERT-EECs were shown to produce extracellular matrix (ECM) components and ECM secretion was modified by estrogen and progesterone (P4). hTERT-EECs expressed inducible and functional endogenous estrogen receptor-alpha (ER-alpha) as demonstrated by estrogen response element reporter assays and induction of P4 receptor (PR). P4 treatment down-regulated PR expression, induced MUC-1 gene activity and resulted in increased ER-beta transcriptional activity. Gene activities of cytokines and their receptors interleukin (IL)-6, leukemia inhibitory factor (LIF), IL-11 and IL-6 receptor (IL6-R), LIF receptor and gp130 relevant to implantation revealed a 17 beta-estradiol (E2)-mediated up-regulation of IL-6 and an E2- and P4-mediated up-regulation of IL6-R in hTERT-EECs. Thus, hTERT-EECs may be regarded as a novel in vitro model to investigate the role of human EECs in steroid hormone-dependent normal physiology and pathologies, including implantation failure, endometriosis and endometrial cancer.

Disturbed transcallosally mediated motor inhibition in children with attention deficit hyperactivity disorder (ADHD).

OBJECTIVE: The aim of this study was to investigate mechanisms of motor-cortical excitability and inhibition which may contribute to motor hyperactivity in children with attention deficit hyperactivity disorder (ADHD). METHODS: Using transcranial magnetic stimulation (TMS), involvement of the motor cortex and the corpus callosum was analysed in 13 children with ADHD and 13 sex- and age-matched controls. Contralateral silent period (cSP) and transcallosally mediated ipsilateral silent period (iSP) were investigated. RESULTS: Resting motor threshold (RMT), amplitudes of motor evoked potentials (MEP) and cSP were similar in both groups whereas iSP-latencies were significantly longer (p<0.05) and their duration shorter (p<0.01) in the ADHD group. For the ADHD group iSP duration tended to increase and iSP latency to decrease with age (n.s.). Conners-Scores did neither correlate with iSP-latencies and -duration nor with children's age. CONCLUSIONS: The shortened duration of iSP in ADHD children could be explained by an imbalance of inhibitory and excitatory drive on the neuronal network between cortex layer III-the projection site of transcallosal motor-cortical fibers-and layer V, the origin of the pyramidal tract. The longer iSP-latencies might be the result of defective myelination of fast conducting transcallosal fibers in ADHD. iSP may be a useful supplementary diagnostic tool to discriminate between ADHD and normal children.

SCC antigen in the serum as an independent prognostic factor in operable squamous cell carcinoma of the cervix.

The aim of this study was to retrospectively examine whether the occurrence of squamous cell carcinoma (SCC) antigen tumour marker in the serum has prognostic significance in operable SCC of the cervix at the International Federation of Gynaecology and Obstetrics (FIGO) stages IA2-IIB. A total of 129 patients who had undergone a radical hysterectomy for SCC of the uterine cervix at the Department of Gynecology of the Martin-Luther University, Halle-Wittenberg in 1991-2000 were included. SCC antigen (Ag) was measured by IMx SCC-Ag microparticle enzyme immunoassay (Abbott Laboratories, Abbott Park, IL, USA). To assess the prognostic value of SCC antigen in the serum, we used a step-by-step multivariate analysis based on the Cox proportional hazard regression model. Using a cut-off value of 3.0 ng/ml, we detected preoperative SCC antigen in the serum as an independent prognostic factor in SCC of the cervix, both for recurrence-free and overall survival (P=0.003 and 0.0078). In this retrospective analysis the value of the SCC antigen tumour marker correlates with prognosis in operable SCC of the cervix, independent of tumour size, pelvic nodal status, cervical stroma infiltration, parametrial spread and tumour grading.

[Possibilities and limits of treatment of aggressive behavior in patients with mental retardation with risperidone]. / Möglichkeiten und Grenzen der Behandlung aggressiven Verhaltens bei Menschen mit geistiger Behinderung mit Risperidon.

Despite definite indication for psychopharmacologic intervention, severe and persistent symptoms of aggressive and self-injurious behaviour still remain a therapeutic challenge. As recent research has demonstrated, not only the dopaminergic and serotonergic but also the endogenous opiate system plays a role in the pathogenesis of self-injurious behaviour. Nevertheless, the efficacy of classical neuroleptics as well as opiate antagonists is questioned. In open and controlled studies, the administration of the atypical neuroleptic risperidone (a serotonin 2A-dopamine D2 antagonist) was associated with a long-term effect in reducing self-injuries. In our clinical trial, 20 mentally retarded adults presenting with severe self-injurious and aggressive behaviour were administered risperidone over a follow-up period of 35 months. Clinical efficacy was measured with the Disability Assessment Schedule (DAS), conducted in a home for people with mental retardation. In 17 patients, a significant reduction in self-injurious behaviour is shown. Besides, there was a significant overall clinical improvement in behaviour.

[Child and adolescent psychiatric aspects of expertising on children suffering from impediments in learning or mental perceptien]. / Kinder- und jugendpsychiatrische Aspekte der Begutachtung von Kindern mit Lernstörungen oder geistiger Behinderung.

Based on the efforts by the legislator to standardize the law for disabled persons and to simplify the accesses to appropriate assistance, procedures of expert reports are exemplarily presented from the aspect of child and adolescent psychiatry. Obliged to the principle of the two aspects for constituting a claim (which is first to set up a diagnosis and then to evaluate the existent or imminent handicap, both serving as the basis for the claim), etiological models, diagnostic - including developmental psychological - and therapeutic approaches in underlying psychiatric disorders of learning difficulties such as attention deficit hyperactivity disorders, pervasive developmental disorders, specific developmental disorders in learning abilities, and mental retardation are described as the participation in social life is either at risk or already affected. With regard these descriptions it is readily recognizable that child and adolescent neuropsychiatry has not only to provide professional competence in cases of appraisal question formulations concerning special assistance in early childhood, determination of special educational needs, and creation of plans for auxilliary interventions, but should also be employed regularly.

Sentinel node procedure in Ib cervical cancer: a preliminary series.

The aim of this study was to determine the diagnostic accuracy and feasibility of sentinel lymph node (SLN) detection using a gamma probe in patients with Figo IB cervical cancer. Between January 1999 and September 2000, 14 patients with cervical cancer, planned for radical hysterectomy were eligible for the study. The day before radical hysterectomy we injected technetium(99)m-labelled nanocolloid in each quadrant of the cervix. Dynamic and static images were recorded using a gamma camera. SLNs were identified intraoperatively using a handheld gamma-detection probe. After resection of SLNs a standard radical hysterectomy with pelvic lymph node dissection was performed. Patients and tumour characteristics were compared with sentinel node detection and with final histopathological and immunohistochemical results. Scintigraphy showed focal uptake in 13 of the 14 patients. Intraoperatively we detected 26 sentinel nodes by gamma probe. In 8 of 13 patients, one or more sentinel nodes were identified unilaterally, in 5 women bilaterally. Histologically positive SLNs were found in only 1 patient. We did not find any false-negative SLN in our series. In conclusion identification of sentinel nodes in cervical cancer is feasible with preoperatively administered technetium(99)m-labelled nanocolloid. A larger series will be required to establish sentinel node detection in cervical cancer for further therapy concepts and planning.

[New knowledge regarding tumor cell inactivation and histological evaluation after radiofrequency therapy. Single case observation and in vitro proof of a new hypothesis]. / Neue Erkenntnisse über Tumorzellinaktivierung und histologische Beurteilbarkeit nach Radiofrequenztherapie. Einzelfallbeobachtung und In-vitro-Nachweis einer neuen Hypothese.

In a study, a radiofrequency (RF) treatment was performed on a patient with a small breast cancer after vacuum biopsy. As usual in cases with a malignant diagnosis, surgical excision and axillary dissection followed. Histopathology revealed some residual tumor in the margin of the cavity. It could not be distinguished from vital tumor on the hematotoxylin eosin (HE) stain. Based on the correlation of MRI and histopathology after subsequent surgical excision, we did, however, presume that the residual was contained within the zone of inactivation. Thus the hypothesis arose that, if too high temperatures can be avoided, it might be possible to inactivate tumor cells without significantly impairing histopathologic assessment. This hypothesis was supported by the following in vitro experiment performed on a fresh specimen: An RF treatment was performed using temperatures up to 70 degrees C only. Half of the specimen underwent HE-staining, the other half vitality testing. The results indicate that if a given temperature range is strictly observed it appears possible to inactivate tissue before tissue sampling, since histopathologic diagnosis will not be impaired. Further technologic improvements may eventually allow to develop a pre-treatment method which might permit to avoid potential hematogenous tumor spread during subsequent biopsy.

Cellular localization of human relaxin-like factor in the cyclic endometrium and placenta.

We have studied the cellular localization of the relaxin-like factor (RLF) in the histologically normal cyclic endometrium collected from days 3--26 of the menstrual cycle. RLF transcripts and protein were detected in the luminal and glandular epithelium and in stromal cells at all stages of the cyclic endometrium. Increased expression of RLF was observed in endometrial tissues in the proliferative as compared to the secretory phase, suggesting that oestrogens affect RLF gene activity in the human endometrium. The cellular localization of RLF transcripts and protein was also determined in first trimester placental tissues obtained from normal and ectopic tubal implantation sites and in third trimester placentae of normal and pre-eclamptic pregnancies. In first trimester placenta, weaker expression of RLF was observed in the syncytiotrophoblast as compared to the underlying cytotrophoblast. Extravillous trophoblast cells constitutively expressed RLF. Trophoblast cells were the main source of RLF in the human placenta and trophoblastic RLF gene activity was unaffected by either the site of implantation or the invasive properties of the cytotrophoblast as demonstrated by samples from patients with tubal implantation and pre-eclampsia respectively. Decidual cells weakly expressed RLF. The presence of unprocessed and cleaved immunoreactive RLF in term placenta was determined by Western analysis. The above results suggest a functional role for both RLF isoforms within normal placental tissue.

Sertoli-Leydig cell tumor.

Sertoli-Leydig cell tumors belong to the group of sex-cord stromal tumors of the ovary. They account for less than 0,5% of all ovarian neoplasms. The majority of these tumors are benign, and almost all are localised unilaterally. Herewith, we describe an ovarian Sertoli-Leydig cell tumor in an 11-year-old girl. Serum levels of estradiol and progesterone were mildly elevated. while testosterone and androstendion levels were raised to around three- and sevenfold upper normal limit respectively on presentation. A left salpingo-oophorectomy was performed. Microscopically, the tumor was intermediately differentiated. At 6 months follow-up, there was neither clinical nor sonographical evidence of recurrence, and almost all sex hormone levels had returned to within normal range. Treatment of this pathological entity has to be individualized according to patient age, stage of tumor and degree of differentiation.

Tenascin-A marker for the malignant potential of preinvasive breast cancers.

OBJECTIVE: Up to now, the mechanisms responsible for progression from noninvasive to invasive breast cancer have remained obscure. Tenascin is an extracellular matrix glycoprotein, present in embryonal and fetal tissues, which is also found in the stroma of various benign and malignant pathologies. We studied the expression and immunohistochemical behavior of tenascin in specimens of invasive and preinvasive breast cancer in order to assess its potential role as a marker for tumor invasion. MATERIALS AND METHODS: Sixty-eight specimens including 29 noninvasive ductal cancers, 12 invasive ductal cancers, 5 adenoses, 7 fibroadenomas, and 15 samples of normal human breast tissue were evaluated. An immunofluorescent microscopic technique was used for analysis of the localization and distribution of tenascin. Paraffin-embedded biopsies were incubated with primary monoclonal anti-tenascin antibodies (1:25, Dako-tenascin, TN2). Subsequently, trimethylrhodamine-isothiocyanate-conjugated secondary antibodies (rabbit anti-mouse immunglobulins (Dakopatts, Denmark) were added to visualize the protein. RESULTS: A significant tenascin expression was observed around the ducts in all samples of patients with preinvasive breast cancers. Intensive staining was also found in the periductal stroma of all specimens of patients with invasive breast cancers. Benign breast lesions showed weaker reactivity. No tenascin expression was detectable in normal human breasts, while tissue samples of in situ cancers presented variable staining intensities positively correlating with the degree of differentiation. CONCLUSION: Tenascin immunofluorescence may prove a suitable and helpful adjunct for diagnosing malignant disease and for predicting the invasive potential of premalignant breast lesions.

Significance of endovaginal ultrasonography in assessing tamoxifen-associated changes of the endometrium. A prospective study.

BACKGROUND: A prospective study was conducted investigating the value of endovaginal ultrasound in the assessment of tamoxifen-associated changes of the endometrium in patients with breast cancer. METHODS: Seventy postmenopausal patients with breast cancer treated with anti-estrogens for at least 6 months were entered. Those with bleeding disorders and/or an endometrial thickness of > or =10 mm found on ultrasonography underwent hysteroscopy and dilatation and curettage (D&C) for further histological evaluation. In 22 patients, positive ultrasound findings could be compared with histopathology. RESULTS: 82% of the 22 patients with positive sonographic findings had a glandular-cystic hyperplasia or a glandular-cystic polyp. No adenomatous hyperplasia or endometrial cancer was observed in our series. CONCLUSION: Vaginal ultrasound represents a useful diagnostic tool to detect tamoxifen-associated changes of the endometrium. A threshold of 10 mm endometrial thickness appears suitable to identify endometrial abnormalities while reducing the rate of false-positive findings to an acceptable level. However, the role of vaginal ultrasound in screening for endometrial cancer or premalignant lesions remains uncertain.