Aromatase inhibitors in men: effects and therapeutic options

Aromatase inhibitors effectively delay epiphysial maturation in boys and improve testosterone levels in adult men Therefore, aromatase inhibitors may be used to increase adult height in boys with gonadotropin-independent precocious puberty, idiopathic short stature and constitutional delay of puberty. Long-term efficacy and safety of the use of aromatase inhibitors has not yet been established in males, however, and their routine use is therefore not yet recommended

Treatment of breast cancer with different antiprogestins: Preclinical and clinical studies

Abstract Treatment with antiprogestins in a new treatment modality for breast cancer. Previously, in rats with DMBA-induced mammary tumors we observed significant growth inhibitory effects of chronic treatment with the antiprogestin mifepristone (RU486). In addition, in 11 postmenopausal breast cancer patients, we observed one objective response, six instances of short-term stable disease, and four instances of progressive disease. Side-effects appeared mainly due to antiglucocorticoid properties of the drug. Increased plasma estradiol levels were observed which probably resulted from ovarian (rat) and adrenal (patients) steroidogenesis. Combined treatment with an antiestrogen in the rat model caused additive growth inhibitory effects. Tumor inhibition after single treatment with mifepristone or tamoxifen was 90 and 75%, respectively. In contrast, when combined, tumor remission similar to that caused by LHRH-agonist treatment (50%) was observed. Even higher tumor remission was found after combined treatment with mifepristone plus LHRH-agonist (75%). In first studies in the rat model we observed significant tumor growth inhibitory effects with two new antiprogestins of seemingly greater potency which cause less unfavorable endocrine side-effects. In conclusion: combined treatment (antiprogestin plus antiestrogen or LHRH-agonist) may be of value in endocrine therapy of breast cancer

Epidemiology and outcome of rib fractures:a nationwide study in the Netherlands

Purpose Rib fractures following thoracic trauma are frequently encountered injuries and associated with a significant morbidity and mortality. The aim of this study was to provide current data on the epidemiology, in-hospital outcomes and 30-day mortality of rib fractures, and to evaluate these results for different subgroups. Methods A nationwide retrospective cohort study was performed with the use of the Dutch Trauma Registry which covers 99% of the acutely admitted Dutch trauma population. All patients aged 18 years and older admitted to the hospital between January 2015 and December 2017 with one or more rib fractures were included. Incidence rates were calculated using demographic data from the Dutch Population Register. Subgroup analyses were performed for flail chest, polytrauma, primary thoracic trauma, and elderly patients. Results A total of 14,850 patients were admitted between 2015 and 2017 with one or more rib fractures, which was 6.0% of all trauma patients. Of these, 573 (3.9%) patients had a flail chest, 4438 (29.9%) were polytrauma patients, 9273 (63.4%) were patients with primary thoracic trauma, and 6663 (44.9%) were elderly patients. The incidence rate of patients with rib fractures for the entire cohort was 29 per 100.000 person-years. The overall 30-day mortality was 6.9% (n = 1208) with higher rates observed in flail chest (11.9%), polytrauma (14.8%), and elderly patients (11.7%). The median hospital length of stay was 6 days (IQR, 3-11) and 37.3% were admitted to the intensive care unit (ICU). Conclusions Rib fractures are a relevant and frequently occurring problem among the trauma population. Subgroup analyses showed that there is a substantial heterogeneity among patients with rib fractures with considerable differences regarding the epidemiology, in-hospital outcomes, and 30-day mortality

Semi-Analytical Models for the Formation of Disk Galaxies II. Dark Matter versus Modified Newtonian Dynamics

We present detailed semi-analytical models for the formation of disk galaxies both in a Universe dominated by dark matter (DM), and in one for which the force law is given by modified Newtonian dynamics (MOND). We tune the models to fit the observed near-infrared Tully-Fisher (TF) relation, and compare numerous predictions of the resulting models with observations. The DM and MOND models are almost indistinguishable. They both yield gas mass fractions and dynamical mass-to-light ratios which are in good agreement with observations. Both models reproduce the narrow relation between global mass-to-light ratio and central surface brightness, and reveal a characteristic acceleration, contrary to claims that these relations are not predicted by DM models. Both models require SN feedback in order to reproduce the lack of high surface brightness dwarf galaxies. However, the introduction of feedback to the MOND models steepens the TF relation and increases the scatter, making MOND only marginally consistent with observations. The most serious problem for the DM models is their prediction of steep central rotation curves. However, the DM rotation curves are only slightly steeper than those of MOND, and are only marginally inconsistent with the poor resolution data on LSB galaxies.Comment: 26 pages, 11 figures. Accepted for publication in Ap

Epidemiology of combined clavicle and rib fractures:a systematic review

Purpose The aim of this systematic review was to provide an overview of the incidence of combined clavicle and rib fractures and the association between these two injuries. Methods A systematic literature search was performed in the MEDLINE, EMBASE, and CENTRAL databases on the 14(th) of August 2020. Outcome measures were incidence, hospital length of stay (HLOS), intensive care unit admission and length of stay (ILOS), duration of mechanical ventilation (DMV), mortality, chest tube duration, Constant-Murley score, union and complications. Results Seven studies with a total of 71,572 patients were included, comprising five studies on epidemiology and two studies on treatment. Among blunt chest trauma patients, 18.6% had concomitant clavicle and rib fractures. The incidence of rib fractures in polytrauma patients with clavicle fractures was 56-60.6% versus 29% in patients without clavicle fractures. Vice versa, 14-18.8% of patients with multiple rib fractures had concomitant clavicle fractures compared to 7.1% in patients without multiple rib fractures. One study reported no complications after fixation of both injuries. Another study on treatment, reported shorter ILOS and less complications among operatively versus conservatively treated patients (5.4 +/- 1.5 versus 21 +/- 13.6 days). Conclusion Clavicle fractures and rib fractures are closely related in polytrauma patients and almost a fifth of all blunt chest trauma patients sustain both injuries. Definitive conclusions could not be drawn on treatment of the combined injury. Future research should further investigate indications and benefits of operative treatment of this injury

Експортно­імпортні операції в Чернігівській губернії на початку ХХ ст.

У статті на основі маловідомих фактів досліджується організація зовнішньої торгівлі в Чернігівській губернії Російської імперії на початку ХХ ст. Показані основні екпортно-імпортні операції, особливості економічного розвитку регіону.В научной статье на основании использования неизвестных ранее фактов исследуется организация внешней торговли в Черниговской губернии Российской империи в начале ХХ века. Показаны основные экспортно-импортные операции и особенности экономического развития региона.In scientific article author research the special organization of foreign trade in Chernigov’s region of Russian empire in the beginning of 20 century. Export-import operations and economic development had illustration in this work

A polymorphism in the glucocorticoid receptor gene may be associated with and increased sensitivity to glucocorticoids in vivo

We investigated whether a polymorphism at nucleotide position 1220, resulting in an asparagine-to-serine change at codon 363 in the glucocorticoid receptor (GR) gene is associated with an altered sensitivity to glucocorticoids. In a group of 216 elderly persons, 13 heterozygotes for the N363S polymorphism were identified by PCR/single strand conformation polymorphism analysis. In 2 dexamethasone (DEX) suppression tests (DSTs), using 1 and 0.25 mg DEX, the circulating cortisol and insulin concentrations were compared between N363S carriers and controls. In the 1-mg DST, there were no differences between N363S carriers and controls, with respect to adrenal suppression, but there was a significantly higher (P < 0.05) insulin response in N363S carriers. In the 0.25-mg DST, a significantly larger (P < 0.05) cortisol suppression and higher (P < 0.05) insulin response were seen in N363S carriers. Comparison of blood pressure, body mass index (BMI), and bone mineral density (BMD) between the N363S carriers and controls showed that N363S carriers had a higher (P < 0.05) BMI but normal blood pressure. There was an obvious trend towards lower age-, BMI-, and sex-adjusted BMD in the lumbar spine in N363S carriers. GR characteristics measured in 41 controls and 9 N363S carriers in peripheral mononuclear leucocytes showed no differences between N363S carriers and controls, with respect to GR number and ligand binding affinity. However, there was a trend towards greater sensitivity to DEX in the carriers' lymphocytes, in a mitogen-induced cell proliferation assay. In transfection assays, the capacity of the codon 363 variant to activate mouse mammary tumor virus promotor-mediated transcription in COS-1 cells was unaltered, when compared with the wild-type GR. We conclude that in 6.0% of our study population, a polymorphism in codon 363 of the GR gene was found. Individuals carrying this polymorphism seemed healthy at clinical examination but had a higher sensitivity to exogenously administered glucocorticoids, with respect to both cortisol suppression and insulin response. Life-long exposure to the mutated allele may be accompanied by an increased BMI and a lowered BMD in the lumbar spine but does not affect blood pressure

Virilization Due to Androgen Hypersecretion in a Patient with Ovarian Leydig Cell Tumor: Diagnostic and Psychosocial Implications

Virilisasi akibat kelebihan hormon androgen yang terjadi pada wanita akan menimbulkan tanda-tanda seperti pembesaran klitoris, perubahan suara, tumbuhnya rambut di wajah dan tubuh yang menjadi ciri khas laki-laki. Virilisasi yang disebabkan oleh tumor ovarium tidak lebih dari 0,5% dari seluruh penyebab. Kami melaporkan kasus virilisasi akibat tumor sel Leydig pada ovarium kiri wanita usia 36 tahun. Kesalahan interpretasi, informasi medis yang saling bertentangan dan saran dari dokter sebelumnya membuat kebingungan dari pasien tersebut. Kami melakukan evaluasi diagnostik yang meliputi gambaran klinik, hormon, pencitraan, pemeriksaan patologi, molekuler serta pemeriksaan psikologi. Pemeriksaan hormon menunjukkan kadar testosteron yang sangat tinggi. Adanya tumor pada ovarium terdeteksi dari pemeriksaan laparoskopi. Biopsi pada ovarium kiri dilakukan oleh karena pasien menolak dilakukan pengangkatan ovarium. Hasil pemeriksaan patologi menunjukkan tumor sel Leydig tanpa adanya tanda keganasan. Pengelolaan menjadi kurang optimal karena faktor sosial budaya yang menghambat walaupun telah dilakukan konseling secara mendalam. Tumor sel Leydig pada ovarium dicurigai apabila terjadi virilisasi pada wanita usia reproduktif disertai peningkatan hormon androgen, massa ovarium pada pemeriksaan pencitraan dan dibuktikan dengan hasil biopsi. Hal ini penting sebelum memberikan saran maupun pengobatan kepada pasien. Kata kunci: diagnostik work up, virilisasi, sel tumor Leydig. ABSTRACT Virilization due to hyperandrogenism in women causes male signs and symptoms such as swelling of the clitoris, deepening of the voice, facial hair and increase in body hair. Virilization is caused by less than 0.5% of all ovarian tumors. Here we report a case of virilizing Leydig cell tumor of the left ovary in a 36 year old woman. Misinterpretation of symptoms, conflicting medical information and advice from previous doctors had confused the patient. We performed a diagnostic evaluation including clinical, hormonal parameters, imaging, anatomical pathology examinations, and psychological assessment. Blood analysis showed a high testosterone level. The presence of an ovarian tumor was confirmed by laparoscopy. Since the patient refused ovariectomy, a biopsy of the left ovary was performed. Pathology showed a Leydig cell tumor without histological signs of malignancy. In spite of extensive explanation and psychological counseling, cultural barriers prevented appropriate treatment. An ovarian Leydig cell tumor should always be considered for a woman in the reproductive age with symptoms of virilization. The diagnosis is suspected on the basis of an ovarian mass on examination and further investigation and should be proven by biopsy. Key words: diagnostic work up, virilization, Leydig cell tumor