Endometrial volume change during spontaneous menstrual cycles: volumetry by transvaginal three-dimensional ultrasound

Objective: At present, only limited data are available on endometrial volume during the menstrual cycle. Most of these studies deal with animal models and use magnetic resonance imaging for volume measuring. The application of three-dimensional ultrasound in endometrial volume estimation is the subject of this study.Setting: Patients visiting the outpatient unit of the division of endocrinology and reproductive medicine of a university hospital.Patient(s): Twenty patients with a history of a normal menstrual cycle were selected.Intervention(s): Ultrasound examinations were performed during a single menstrual cycle in addition to routine laboratory tests.Main Outcome Measure(s): Uterus-endometrial volume ratio.Result(s): Data from 18 patients could be evaluated. In 81 examinations the endometrium volume could be determined. Mean endometrial volume measured by three-dimensional ultrasound was 1.23 cm'. Mean uterus volume was 48.93 cm3. The change of the uterus-endometrial volume ratio showed a good correlation with the day of menstrual cycle. Quadratic regression analysis of volume and cycle length was R² = 0.432.Conclusion(s): Three-dimensional ultrasound allows assessment of volume data of the female internal genitalia. In this study changes of the endometrial volume in menstrual cycles were measured. Additional studies are required to give information on the clinical impact of this new technique of endometrial volume estimation.     

Angiogenesis in Vulvar Intraepithelial Neoplasia

Vulvar intraepithelial neoplasia (VIN) has been reported to be a precursor of invasive vulvar cancer. Switching to the angiogenic phenotype is considered a key step in tumor growth. Microvessel density (MVD) and vascular endothelial growth factor (VEGF), a highly angiogenic peptide, are important parameters of tumor angiogenesis. Forty-three histologic slides with 38 VIN I–III lesions were immunohistochemically stained for factor VIII-related antigen (F8-RA) and 44 slides with 37 VIN I–III for VEGF, since F8-RA reliably highlights tumor microvessels. Determination of MVD and VEGF expression was done by counting microvessels and VEGF-positive cells at a magnification of 200× and 400×. The highest concentration of F8-RA-stained MVD and VEGF expression was found at a small subepithelial area at the border of the VIN lesion to the stroma underneath but concentrations were low in all specimens of normal epithelium. High VEGF expression was significantly correlated to high MVD. For both MVD and VEGF expression the differences between VIN I and VIN III and between VIN II and VIN III were statistically significant (P< 0.0001). VIN III lesions are the clinical relevant precursors of invasive cancer of the vulva, as outlined by intense expression of VEGF protein and a highly dense network of microvessels underlying the dysplastic epithelium.     

The use of an ambulatory,automatic sleep recording device (QUISI™ Version 1.0) in the evaluation of primary snoring and obstructive sleep apnoea

The use of an ambulatory, automatic sleep recording device (QUISI? Version 1.0) in the evaluation of primary snoring and obstructive sleep apnoea Electroencephalogram (EEG) evaluation with polysomnography (PSG) according to the Rechtschaffen & Kales (R&K) rules is time and cost consumptive, but ambulatory polygraphy systems do not allow EEG recording routinely. As a consequence, the number of sleep disordered events cannot be calculated exactly. QUISI is a one‐channel, self‐applicable ambulatory EEG recording device. The present study was designed as a prospective, non‐randomized clinical trial. This investigation evaluated the results of 40 patients with primary snoring and obstructive sleep apnoea measured with level 1 PSG and QUISI simultaneously. Fifteen patients (37.5%) were primary snorers with normal sleep profiles, whereas 25 patients (62.5%) suffered from obstructive sleep apnoea (OSA) with a Respiratory Disturbance Index (RDI) of 38.6 ± 23.8. The mean total sleeping time (TST) was underestimated by 4.5%, while Sleep Efficiency Index (SEI) was understimated by 4.6% by the QUISI device compared with PSG. The correlation between the QUISI and the PSG estimates for single sleep stages demonstrated only moderate correlation. The statistical significance for sleep stage 2 was r = 0.42, P = 0.002; for sleep stage 3/4, r = 0.31, P = 0.02; and for WAKE, r = 0.33, P = 0.01. Sleep stage 2 as well as sleep stage 3/4 were underestimated by QUISI substantially (difference: ?5.6% and ?10.3%), while WAKE was overestimated by QUISI to a larger amount (difference: +10.4%). Sensitivity and specificity of QUISI to recognize pathological sleep profiles compared with PSG/R&K were 0.92 and 0.96 respectively. QUISI is able to evaluate normal versus altered sleep profiles in patients with primary snoring and OSA. Comparing the quartile ranges, we found substantial differences between QUISI and PSG/R&K. QUISI gives an impression of sleep architecture and objective verification of a sleep disturbance in an ambulant setting but cannot replace the sleep laboratory‐based PSG.     

Congenital pupillary-iris-lens membrane with goniodysgenesis.

BACKGROUND: A unilateral congenital pupil-iris-lens membrane with goniodysgenesis syndrome, not benign tunica vasculosa lentis, was first described by Cibis et al. One of three cases developed angle closure. Robb described catastrophic vision loss from angle closure in one of his seven cases. METHODS: We did a retrospective review of previously unreported cases of pupil-iris-lens membrane with goniodysgenesis seen in our practices. RESULTS: We report the clinical spectrum of a further nine cases, three of which needed surgery for angle closure, two of which needed surgery for clearing the visual axis. CONCLUSION: Congenital pupil-iris-lens membrane with goniodysgenesis is a unilateral membrane clearly differentiated from benign persistent tunica vasculosa lentis tissue. The membrane represents ectopic iris on the lens with abnormal iris stroma and chamber angle from aberrant induction, migration, or regression of neural crest cells. The membrane can be progressive. Catastrophic vision loss from angle closure can occur and may be controlled with surgery. Surgery may be needed to open the visual axis even when glaucoma is not present and may prevent angle closure.     

Analysis of concerted expression of angiogenic growth factors in acute myeloid leukemia: expression of angiopoietin-2 represents an independent prognostic factor for overall survival.

PURPOSE: Bone marrow neoangiogenesis plays an important pathogenetic and possible prognostic role in acute myeloid leukemia (AML). Members of the vascular endothelial growth factor (VEGF) and angiopoietin family represent the most specific inducers of angiogenesis secreted by AML blasts. We therefore correlated expression of angiogenic factors with clinical variables. PATIENTS AND METHODS: We investigated the expression of VEGF-A, VEGF-C, angiopoietin-1 (Ang1), angiopoietin-2 (Ang2), and the receptor Tie2 by quantitative polymerase chain reaction in a cohort of 90 patients younger than 61 years with de novo AML entered into the German AML Süddeutsche H?moblastose Gruppe Hannover 95 trial. Uni- and multivariate analyses were performed using clinical and gene expression variables. RESULTS: Univariate analysis of overall survival indicated the following variables as prognostic factors: good response on a day-15 bone marrow examination after initiation of induction chemotherapy, karyotype, and high Ang2 expression. In multivariate analysis, only bad response and log Ang2 expression remained of statistical significance, with a hazard ratio of 3.51 (95% CI, 1.91 to 6.47) and 0.75 (95% CI, 0.61 to 0.91), respectively. Subgroup analysis suggested that the prognostic impact of Ang2 expression was especially evident in cohorts with low VEGF-C and Ang1 mRNA levels. CONCLUSION: These results show that expression of Ang2 represents an independent prognostic factor in AML. Additional research into interactions of angiogenic cytokines in the pathogenesis of bone marrow angiogenesis in AML is warranted.     

Specialized DNA arrays for the differentiation of pancreatic tumors.

PURPOSE: Malignant tumors of the pancreas are frequently indistinguishable from inflammatory tumors arising in the context of a chronic pancreatitis with the use of conventional imaging techniques. Thus, cytologic analysis of cells obtained by abdominal ultrasound, computed tomography, or endoscopic ultrasound-guided fine needle aspiration biopsy is required for diagnosis. However, the reliability of cytologic analyses of pancreatic fine needle aspirates remains unsatisfactory, with a diagnostic accuracy of < or =80%. The purpose of the current study was therefore to develop a novel diagnostic approach based on expression profiling of biopsy material using a specialized diagnostic cDNA array. EXPERIMENTAL DESIGN: Previous gene expression profiling studies were reevaluated to design a 558-feature diagnostic array. Minimal amounts of residual material from pancreatic cytology samples as well as surgically resected tumor and control tissue specimens were analyzed using the diagnostic array and a newly developed statistical classification system. RESULTS AND CONCLUSIONS: Our diagnostic approach resulted in 95% accurate differentiation between ductal adenocarcinomas and nonmalignant tumors of the pancreas. The diagnostic array, in conjunction with conventional diagnostic procedures, is thus suitable to significantly improve the reliability of pancreatic cancer diagnostics and can be expected to become a valuable new tool in the routine workup of suspect masses in the pancreas.     

Urinary acetylated metabolites and N-acetyltransferase-2 genotype in human subjects treated with a para-phenylenediamine-containing oxidative hair dye.

In the organism of mammals, important detoxification pathways of arylamines are catalysed by N-acetyltransferase 2 (NAT2). A recent case-control epidemiology study suggested that human NAT2 slow acetylators exposed to oxidative hair dyes may be at greater risk to develop bladder cancer. We therefore profiled urinary [(14)C]-metabolites and NAT2 genotype in eight human subjects following treatment with a dark-shade oxidative hair dye containing [(14)C]-para-phenylenediamine (PPD). Genotyping identified three subjects as slow, and five subjects as intermediate NAT2 acetylators. Within 24 h after treatment, the study subjects excreted a mean total of 0.43+/-0.24% of the applied [(14)C] in the urine, where five different metabolites were found. The major urinary metabolites were concluded to be N-mono-acetylated and N,N'-diacetylated PPD. They were present in all urine samples and amounted to 80-95% of the total urinary [(14)C]. Another metabolite, possibly a glucuronic acid conjugate, was found in 6/8 urine samples at 5-13% of the total urinary [(14)C]. All metabolites appeared to be related to PPD, no evidence of the presence of high-molecular weight dye-intermediates or corresponding metabolites was found. The metabolite profile in the study subjects showed no significant differences between the NAT2 intermediate and NAT2 slow acetylator subgroups. Urine of NAT2 slow acetylators contained N-mono-acetylated-PPD at 42.2+/-10.2% and N,N'-di-acetylated-PPD at 54.1+/-7.6% of total urinary radioactivity, while the corresponding values of intermediate acetylators were 46.0+/-8.9% and 45.7+/-9.9%, respectively. Overall, our results suggest that the human acetylation rate of PPD after topical application is independent of the NAT2 genotype status, most likely due to metabolism by epidermal NAT1 prior to systemic absorption.     

L-Serine Treatment is Associated with Improvements in Behavior,EEG, and Seizure Frequency in Individuals with GRIN-Related Disorders Due to Null Variants

Pathogenic missense variants in GRIN2A and GRIN2B may result in gain or loss of function (GoF/LoF) of the N-methyl-D-aspartate receptor (NMDAR). This observation gave rise to the hypothesis of successfully treating GRIN-related disorders due to LoF variants with co-agonists of the NMDAR. In this respect, we describe a retrospectively collected series of ten individuals with GRIN2A- or GRIN2B-related disorders who were treated with L-serine, each within an independent n-of-1 trial. Our cohort comprises one individual with a LoF missense variant with clinical improvements confirming the above hypothesis and replicating a previous n-of-1 trial. A second individual with a GoF missense variant was erroneously treated with L-serine and experienced immediate temporary behavioral deterioration further supporting the supposed functional pathomechanism. Eight additional individuals with null variants (that had been interpreted as loss-of-function variants despite not being missense) again showed clinical improvements. Among all nine individuals with LoF missense or null variants, L-serine treatment was associated with improvements in behavior in eight (89%), in development in four (44%), and/or in EEG or seizure frequency in four (44%). None of these nine individuals experienced side effects or adverse findings in the context of L-serine treatment. In summary, we describe the first evidence that L-serine treatment may not only be associated with clinical improvements in GRIN-related disorders due to LoF missense but particularly also null variants.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13311-021-01173-9.     

Anticoagulant action of melagatran: a comparison between neonates and adults using calibrated automated thrombography (CAT)

In the present study, we comparatively evaluated the anticoagulant efficacy of the new direct thrombin inhibitor melagatran in cord vs. adult plasma. In contrast to heparin, melagatran does not require antithrombin as a cofactor. Thus, anticoagulant treatment with melagatran is of special interest in neonatal patients, whose plasma is relatively deficient in antithrombin. We evaluated the anticoagulant action of increasing amounts of melagatran (0.1–2.0 μmol/l) in both cord and adult plasma by means of calibrated automated thrombography (CAT) with respect to the lag time until the onset of thrombin formation, time to thrombin peak maximum (TTP), endogenous thrombin potential (ETP), and thrombin peak height. Melagatran exhibited approximately the same ability to prolong lag times or TTPs in both cord and adult plasma. Similar concentrations (IC₅₀) of melagatran were required to double the lag times (0.44±0.04 μmol/l vs. 0.52±0.05 μmol/l) or to double the TTPs (0.91±0.08 μmol/l vs. 1.06±0.09 μmol/l) in cord vs. adult plasma. Melagatran exhibited a higher ability to suppress ETPs or thrombin peak heights in cord vs. adult plasma. Markedly lower concentrations (IC₅₀) of melagatran were required to suppress ETPs (0.27±0.03 μmol/l vs. 0.70±0.06 μmol/l) or thrombin peak heights by 50% (0.29±0.03 μmol/l vs. 0.53±0.04 μmol/l) in cord vs. adult plasma. We conclude that our results suggest a higher ability of melagatran to suppress thrombin formation in cord vs. adult plasma. Thus, lower amounts of melagatran might be required in neonates undergoing antithrombotic therapy.