The impact of biostatistics on hazard characterization using in vitro developmental neurotoxicity assays.

In chemical safety assessment, benchmark concentrations (BMC) and their associated uncertainty are needed for the toxicological evaluation of in vitro data sets. A BMC estimation is derived from concentration-response modelling and results from various statistical decisions, which depend on factors such as experimental design and assay endpoint features. In current data practice, the experimenter is often responsible for the data analysis and therefore relies on statistical software, often without being aware of the software default settings and how they can impact the outputs of data analysis.

A human iPSC-based in vitro neural network formation assay to investigate neurodevelopmental toxicity of pesticides.

Proper brain development is based on the orchestration of key neurodevelopmental processes (KNDP), including the for­mation and function of neural networks. If at least one KNDP is affected by a chemical, an adverse outcome is expected. To enable a higher testing throughput than the guideline animal experiments, a developmental neurotoxicity (DNT) in vitro testing battery (DNT IVB) comprising a variety of assays that model several KNDPs was set up.

Establishment of a human cell-based in vitro battery to assess developmental neurotoxicity hazard of chemicals.

Developmental neurotoxicity (DNT) is a major safety concern for all chemicals of the human exposome. However, DNT data from animal studies are available for only a small percentage of manufactured compounds. Test methods with a higher throughput than current regulatory guideline methods, and with improved human relevance are urgently needed.

Reliable identification and quantification of neural cells in microscopic images of neurospheres.

Neurosphere cultures consisting of primary human neural stem/progenitor cells (hNPC) are used for studying the effects of substances on early neurodevelopmental processes in vitro. Differentiating hNPCs migrate and differentiate into radial glia, neurons, astrocytes, and oligodendrocytes upon plating on a suitable extracellular matrix and thus model processes of early neural development. In order to characterize alterations in hNPC development, it is thus an essential task to reliably identify the cell type of each migrated cell in the migration area of a neurosphere.

Neurodevelopmental toxicity assessment of flame retardants using a human DNT in vitro testing battery.

Due to their neurodevelopmental toxicity, flame retardants (FRs) like polybrominated diphenyl ethers are banned from the market and replaced by alternative FRs, like organophosphorus FRs, that have mostly unknown toxicological profiles. To study their neurodevelopmental toxicity, we evaluated the hazard of several FRs including phased-out polybrominated FRs and organophosphorus FRs: 2,2',4,4'-tetrabromodiphenylether (BDE-47), 2,2',4,4',5-pentabromodiphenylether (BDE-99), tetrabromobisphenol A, triphenyl phosphate, tris(2-butoxyethyl) phosphate and its metabolite bis-(2-butoxyethyl) phosphate, isodecyl diphenyl phosphate, triphenyl isopropylated phosphate, tricresyl phosphate, tris(1,3-dichloro-2-propyl) phosphate, tert-butylphenyl diphenyl phosphate, 2-ethylhexyl diphenyl phosphate, tris(1-chloroisopropyl) phosphate, and tris(2-chloroethyl) phosphate. Therefore, we used a human cell-based developmental neurotoxicity (DNT) in vitro battery covering a large variety of neurodevelopmental endpoints.

The impact of hip fracture on health-related quality of life and activities of daily living: the SPARE-HIP prospective cohort study.

Purpose: The medical morbidity and mortality associated with neck of femur fractures is well-documented, whereas there is limited data for patient-reported outcomes. The aim of this study was to characterize the impact of neck of femur fractures on activities of daily living and patient-reported health-related quality of life.

Methods: Design and participants: Multicentric prospective cohort study.

The association between intrauterine inflammation and spontaneous vaginal delivery at term: a cross-sectional study.

Background: Different factors contribute to the onset of labor at term. In animal models onset of labor is characterized by an inflammatory response. The role of intrauterine inflammation, although implicated in preterm birth, is not yet established in human term labor.

Effects of 15 months of 17 beta-estradiol and dydrogesterone on systolic cardiac function according to quantitative and Doppler echocardiography in healthy postmenopausal women.

Objective: Our goal was to investigate the short-term and intermediate effects of low-dose hormone replacement therapy on echocardiographic parameters of cardiac function in healthy postmenopausal women.

Study Design: In a prospective, controlled study 30 healthy postmenopausal women (mean age, 52 +/- 3 years) were randomly assigned to 2 groups. Women in the hormone replacement therapy group (n = 15) received 1 mg micronized 17 beta-estradiol daily sequentially combined with 5 or 10 mg dydrogesterone for 14 days of each 28-day cycle during 12 months and thereafter 2 mg 17 beta-estradiol combined with 10 mg dydrogesterone for a period of 3 months.

Ultrasound assessment of the endometrium in healthy, asymptomatic early post-menopausal women: saline infusion sonohysterography versus transvaginal ultrasound.

Objective: To exclude pre-existing endometrial pathology in asymptomatic early post-menopausal women before starting hormone replacement therapy by transvaginal ultrasound (TVS) and saline infusion sonohysterography (SIS).

Methods: In a cross-sectional study, 148 healthy women (mean age, 51.1 years; range, 46-59 years) underwent ultrasound evaluation of the endometrium before participation in a clinical trial.

Impaired procoagulant-anticoagulant balance during hormone replacement therapy? A randomised, placebo-controlled 12-week study.

Unlabelled: In this randomised, placebo-controlled 12-week study, sixty healthy postmenopausal women received either placebo (N = 16) or daily 2 mg micronised oestradiol, either unopposed (N = 16, E2 group) or combined with a progestagen for 14 days of each cycle (N = 28, E2+P group).

Results: As compared to placebo, plasma levels of AT III were reduced only in the E2 group (approximately 28%), plasma levels of protein C decreased only in the E2+P group (approximately 4%) and plasma levels of protein S decreased in both the E2 and E2+P group (approximately 21%). In both the E2 and E2+P groups, the plasma levels of factor VII (antigen and activity) showed a borderline significant increase (approximately 10%), whereas no significant change was observed in active factor VII.

Short-term hormone replacement therapy: reduced plasma levels of soluble adhesion molecules.

Background: Epidemiological data have suggested that the use of hormone replacement therapy (HRT) is associated with a decreased risk of cardiovascular disease. Vascular endothelium and adhesion molecules play an important role in the initiation and progression of atherosclerosis.

Material And Methods: Prospective, randomized, placebo-controlled 12-week study.

Increased C-reactive protein levels during short-term hormone replacement therapy in healthy postmenopausal women.

Objective: To study the short-term effect of unopposed oestradiol (E2) and sequentially combined hormone replacement therapy (E2 + P) on C-reactive protein (CRP) in healthy postmenopausal women.

Design: Prospective, randomised, placebo-controlled 12-week study. Sixty healthy.

[An unusual bone scintigram in osteomyelitis. A case report].

Despite hyperemia in the blood-pool phase of bone scintigraphy with 99mTc-MDP there was an decreased concentration of the nuclide in a 7-year-old boy with acute osteomyelitis of the femur. In addition to inflammatory destruction of the bone tissue, the other reason for this surprising scintigraphic finding might be a reduced blood flow because of thrombotic occlusion or compression of bone-supplying vessels.

[Malignant hyperthermia during cataract extraction in an elderly patient].

The case of a 67-year-old patient who suffered an episode of malignant hyperthermia during the extraction of a cataract is described. The outcome was favourable in spite of the lack of sodium dantrolene. Twenty months later the patient was operated on the contralateral eye with local anesthesia presenting no complications.

Clinical follow-up after surgery of lumbar disc prolapses. A critical analysis.

A retrospective clinical study was made on 987 patients with lumbar disc disease treated by discectomy. All patients had been operated on in the Department of Neurosurgery (University-Hospital Mainz). 545 patients were males, and 442 females (1.

The effects of long term testosterone administration on pulsatile luteinizing hormone secretion and on ovarian histology in eugonadal female to male transsexual subjects.

Polycystic ovarian disease (PCOD) is associated with elevated serum LH and (sub)normal FSH levels, while serum androgen levels are often elevated. To clarify the role of androgens in this abnormal pattern of gonadotropin secretion, LH secretion was studied in 1) 9 eugonadal female to male transsexual subjects before and during long term (6 months) testosterone (T) administration (250 mg/2 weeks, im), and 2) in a woman with an androgen-secreting ovarian tumor both before and after surgical removal of the tumor. Finally, we studied the effects of high serum androgen levels on ovarian histology in 3) 26 transsexual subjects after long term (9-36 months) T administration (250 mg/2 weeks, im) to assess whether T-induced ovarian abnormalities are similar to those that occur in women with PCOD.

Effects of long-term testosterone administration on gonadotropin secretion in agonadal female to male transsexuals compared with hypogonadal and normal women.

We investigated the effects of long term testosterone (T) administration on pulsatile gonadotropin secretion in agonadal women and the effects of estradiol (E2) on gonadotropin secretion in eugonadal women in the follicular phase of the menstrual cycle. We studied 4 groups: A) 28 eugonadal women in the early follicular phase of the menstrual cycle, B) 11 hypogonadal women, C) 13 agonadal female to male (f-t-m) transsexuals treated for at least 3 months with 120-160 mg T undecanoate (TU)/day, orally, and D) 5 agonadal f-to-m transsexuals treated for at least 6 months with 250 mg of a mixture of testosterone esters, im (im T-esters), every 2 weeks. The eugonadal women in the early follicular phase had a mean serum E2 level of 193 +/- 94 (+/- SD) pmol/L, significantly higher (P less than 0.

Luteinizing hormone secretion patterns in boys at the onset of puberty measured using a highly sensitive immunoradiometric assay.

Pulsatile LH secretion was studied in 3 prepubertal and 11 early pubertal boys by measuring plasma LH concentrations at 10-min intervals from 1200-1800 h and from 2400-0600 h using an immunoradiometric assay with a lower limit of detection of 0.10 IU/L. Plasma testosterone (T) was measured hourly.

Effects of opiate receptor blockade on gonadotrophin secretion before and after administration of the oestrogen receptor blocker tamoxifen in eugonadal men.

Both gonadal steroids and endogenous opioid peptides (EOPs) exert an inhibitory effect on gonadotrophin secretion. It is thought that the negative feedback action of the gonadal steroids, testosterone (T) and oestradiol (E2), on the gonadotrophin secretion is mediated by EOPs. To assess the effects of EOPs and oestrogen and their interrelationship on pulsatile LH secretion we studied two groups of eugonadal men.

Estrogen-induced prolactinoma in a man.

Prolactinomas can be induced in rats by large doses of estrogens. Whether prolactinomas can be induced in humans by estrogens, however, is not known. This report describes the development of a prolactinoma in a man with previously normal plasma PRL levels after the administration of pharmacological doses of estrogen.

Divergent effects of the antiestrogen tamoxifen and of estrogens on luteinizing hormone (LH) pulse frequency, but not on basal LH levels and LH pulse amplitude in men.

We studied the role of estrogens on LH pulse modulation in men in two ways. Firstly, we compared LH pulse frequency and amplitude in 13 normal men before and after 6 weeks administration of the antiestrogen tamoxifen (10 mg twice daily). Secondly, we compared LH pulse frequency and amplitude between a group of 10 agonadal men not receiving sex steroid treatment and a group of 9 agonadal men (male to female transsexuals) continuously treated with 50 micrograms ethinyl estradiol/day.

Induction of first cycles in primary hypothalamic amenorrhea with pulsatile luteinizing hormone-releasing hormone: a mirror of female pubertal development.

During pubertal development in girls, the attainment of regular ovulatory menstrual cycles usually is preceded by cycles that are either anovulatory or show a defective luteal phase. It is not known whether these defective cycles are caused by inadequate luteinizing hormone-releasing hormone (LH-RH) secretion or by an inadequate response of the pituitary-ovarian axis to LH-RH stimulation. To shed new light on this matter, the authors analyzed endocrine data from 12 menstrual cycles induced by pulsatile LH-RH therapy in five women with primary amenorrhea of hypothalamic origin.